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Performance anxiety: How to ease stage fright
The violin is slippery in my grasp. I hear the thud of my foot tapping, but the tempo feels wrong. I’m aware of my chest pounding, a lump in my throat, and heat rising from my face. Everyone is watching me, waiting for me to make a mistake.
Why can’t I stop my hand from trembling? I can only watch as the bow jumps noisily across the strings. I should have practiced more. My mind goes blank, and I miss the page turn.
Silence. I blink, and the lights blind me as the applause comes, thankfully, and I exhale and run off the stage as the curtain closes.
Well-known performing artists—Sir Laurence Olivier, Kim Basinger, Peter O’Toole, Richard Burton, Barbra Streisand, and Luciano Pavarotti —have described bouts with acute stage fright. Performance anxiety can occur with acting, singing, or playing a musical instrument, and with nonartistic performances such as public speaking, oral examinations, competing in sporting events, sexual activity, using public restrooms, or being watched while doing a task such as surgery, eating, or writing.2
Like social phobia, performance anxiety probably develops in accomplished artists and not-so-famous individuals because of a mélange of genetic factors, innate temperament, parental influences, conditioning events, and cognitive influences.3
NORMAL VS. ABNORMAL FEAR
Performance anxiety is characterized by persisting, distressful apprehension about—or actual impairment of—performance skills to a degree unwarranted by the individual’s aptitude, training, and preparation.1 Not all performance anxiety qualifies as a mental disorder; for example, though 85% of the population experiences discomfort about public speaking,4 this anxiety does not impair most people’s ability to function.
Mild to moderate anxiety is normal and motivating in performances.5 However, anxiety’s effect on performance does not follow a bell-shaped curve, wherein moderate anxiety promotes optimal performance.6 Instead, a catastrophic model is more accurate: increasing anxiety is helpful until a certain threshold is reached, then performance plunges.7
Diagnostic criteria. DSM-IV-TR describes performance anxiety as a form of social phobia (or social anxiety disorder) characterized by marked and persistent fear of social or performance situations in which embarrassment or humiliation might occur. Approximately 13% of adults experience social phobia,8 and about 2% suffer from severe discrete performance anxiety.9
Performance anxiety does not completely overlap with social phobia, however. Test-taking anxiety and writer’s block, which can occur in a nonpublic context, do not fit neatly into the social phobia category.2 Thus, some performance anxiety forms are better grouped as another type of anxiety disorder, such as specific phobia (Figure).
Figure Performance anxiety features overlap with other anxieties
Performance anxiety is not easy to categorize. It is situational anxiety that occurs in a public context and overlaps with but does not entirely match diagnostic criteria for specific phobia, social anxiety, or panic disorder and generalized anxiety.
DIFFERENTIAL DIAGNOSIS
Social anxiety? Ask the patient about all situations that provoke anxiety to differentiate between:
- discrete performance anxiety (1 or 2 performance situations that provoke anxiety)
- and generalized social anxiety (3 or more situations that provoke anxiety).9
Individuals with “trait” anxiety may exhibit innate shyness and are considered to have generalized social phobia. Those with “state” anxiety experience anxiety in specific situations or circumstances and are more aptly described as having discrete performance anxiety.10 Whereas persons with social phobia may avoid the feared activity without inner conflict, those with performance anxiety are committed to performing the activity and are distressed when unable to perform.9
Specific phobia? A specific phobia is a circumscribed fear of a specific object, situation, or activity from which a grim outcome is feared. Specific phobia usually has no performance aspect or fear of embarrassment or failure.
Some clinicians consider certain performance anxieties—such as writer’s block, test-taking anxiety, paruresis, and even fear about sexual performance—to be specific phobias. Because performance anxieties and phobias share some cognitive and behavioral components, their treatments are similar and use of medication is controversial.
General medical condition? Perform or refer the patient for a thorough medical evaluation before you diagnose performance anxiety, as endocrine, cardiovascular, respiratory, and circulatory abnormalities can mimic or exacerbate anxiety disorders. Also consider substance abuse or withdrawal as possible causes of anxiety.
PATIENT EVALUATION
Family history. Individuals with social anxiety often report a family history of generalized social anxiety, panic disorder, or major depressive disorder.3 Similar findings seem plausible for persons with discrete performance anxiety, although comparable family history data have not been reported.
Cognitive symptoms. Four cognitive distortions are common in persons with social phobia (Table 1).11 These negative thoughts are presumably the same for performance anxiety, at least when it is a sub-type of social phobia.
Somatic symptoms. Persons with performance anxiety tend to have heightened awareness of hyperadrenergic arousal symptoms (Table 2), sometimes in all body systems. Symptoms may resemble those of a panic attack.
Behavioral symptoms. Behavioral symptoms include stuttering, mumbling, trembling voice, yawning, biting nails or lips, gritting jaw, poor eye contact, shuffling or tapping feet, unnatural or rigid postures or movements, warming up too fast or too slowly, wearing excessive makeup, or smiling abnormally. A performer may forget to carry out a routine task such as blinking, moistening lips, or turning a page of music.
These behaviors may perpetuate and reinforce anxiety by eliciting negative reactions from an audience and fulfilling the performer’s pessimistic expectations. The therapist can identify these maladaptive behaviors and target them for treatment.
Table 1
4 cognitive distortions that underlie performance anxiety
|
Table 2
Somatic symptoms of performance anxiety
| Bodily system | Symptoms |
|---|---|
| Autonomic | Blushing, diaphoresis, dry mouth |
| GI, urologic | Urinary or bowel urgency, GI discomfort |
| Cardiovascular | Tachycardia, palpitations |
| Neuromuscular | Muscle tension, tremor, paralysis |
PSYCHIATRIC COMORBIDITY
About one-third of individuals with performance anxiety have psychiatric comorbidities.9 Most common are other anxiety disorders, specifically the generalized form of social phobia, generalized anxiety disorder, panic disorder, or specific phobia.12 Mood disorders are less common. We also recommend monitoring for eating disorders because some performing artists are driven to maintain high physical appearance standards.
Personality disorder comorbidities with performance anxiety have not been studied. Some experts believe that avoidant personality and social phobia are the same conditions expressed to varying degrees on a continuum.13 Other personality disorders to consider include schizoid, paranoid, and obsessive-compulsive personalities.
Alcohol and substance use disorders are highly comorbid with performance anxiety. Alcohol use decreases public speaking anxiety,14 and approximately 6% of orchestral musicians use alcohol before a performance.15 For comparison, approximately 16% of patients who present for treatment of generalized anxiety disorder abuse alcohol, often as an attempt to self-medicate.16
TREATMENT PLANNING
Just as performance anxiety’s diagnostic classification may vary, so may treatment. Pharmacologic interventions and psychotherapy for social and specific phobias are similar. Some clinicians favor a multimodal approach addressing behavior, affect, sensation, imagery, cognition, interpersonal relationships, and biological factors.9
The performing arts community is competitive, and individuals may have differing standards about what treatments are acceptable. Some may view using medications as “cheating” or an admission of professional failure. A performer may feel medication gives an unfair advantage, that respect would be lost if others found out, or that taking medication before performing is similar to steroid use by athletes.17,18
Medication vs. psychotherapy. Medication can help diminish anxiety’s physical symptoms, but certain psychotherapies rely on these somatic symptoms for effective treatment and extinguishing of responses. Concurrent use of medications and psychotherapy for social phobia is common in everyday practice, although some studies find the combination no more effective than either treatment alone.11 Symptoms appear less likely to return after cognitive-behavioral therapy (CBT) ends than after medication is discontinued.16
Discuss treatment options with the patient. A patient who feels unable to perform without medication may develop psychological dependency. Conversely, a patient may not be able to afford the full course of psychotherapy needed for positive results. For performing artists, longer visits that incorporate medication management with psychotherapy may be more successful than brief, symptom-targeted visits.
MEDICATION MANAGEMENT
All medication use for performance anxiety is off-label. The most common choices are short-acting agents such as beta blockers or benzodiazepines (Table 3).
Table 3
Medications used to treat performance anxiety*
| Medication | Typical dosage | Possible side effects |
|---|---|---|
| Beta blockers | Medical: sedation, fatigue, dizziness, ataxia, nausea, sexual dysfunction Psychiatric:insomnia, nightmares, depression Contraindications: heart failure, bradycardia, breathing difficulties, hypotension | |
| Propranolol | 10 to 40 mg | |
| Nadolol | 20 to 120 mg | |
| Atenolol | 50 to 100 mg | |
| Benzodiazepines | Performance decrement, amnesia, sedation, discontinuation symptoms, tolerance, abuse potential | |
| Clonazepam | 0.25 to 0.5 mg | |
| Lorazepam | 0.5 to 1 mg | |
| * Off-label use; taken as-needed approximately 1 hour before performance | ||
Beta blockers can relieve autonomic and somatic symptoms such as tachycardia, tremor, and stuttering when used in low doses as needed for mild to moderate circumscribed performance anxiety.16,19 Propranolol, 10 mg about 1 hour before the performance, is most often prescribed.
Before prescribing a beta blocker, evaluate the patient’s medical history and cardiovascular status, including blood pressure and pulse. Have the patient try a test dose before the first live performance to check for side effects and tolerability (Table 3).16,19
Benzodiazepines have been used to treat social anxiety, but controlled studies have not reliably addressed their efficacy in performance anxiety. Advise the patient to abstain from alcohol when taking these medications (Table 3).
PSYCHOTHERAPY OPTIONS
CBT with components of exposure and retraining can ameliorate performance anxiety.10,20
Many performers forgo normal childhood social experiences to hone their talents, at times sacrificing sound coping skills.17 CBT’s goal is to help them reduce negative biases and restructure cognitive processes to function better at whatever task is at hand. This involves teaching them to:
- recognize pessimistic thoughts that occur before, during, and after performances
- challenge the accuracy of these thoughts
- replace them with rational, helpful thoughts based on the assimilated information.11
Exposure therapy can help individuals face feared activities so that counter-conditioning through habituation and extinction can safely occur. Useful strategies include imagination, role play, confrontation, videotaping, and homework assignments.11
Experiencing anxiety is a component of exposure therapy. Thus, some clinicians avoid using concomitant medication that might decrease anxiety’s physical symptoms and interfere with the exposure process.21
Relaxation training can help the patient recognize and respond to autonomic and physical arousal during a performance.11 For example, progressive muscle relaxation can be practiced first in session and then as homework.
Social skills training can help patients identify and change anxiety behaviors that cause negative audience reactions. Tools to help direct the patient towards more appropriate behaviors include modeling, behavior rehearsal, corrective feedback, social reinforcement, and homework assignments such as videotaping performances.11 For public speaking anxiety, vocal and physical skills training10 and computerized virtual reality courses can help.4
Interpersonal therapy may be useful, based on the premise that performance anxiety occurs within a social and interpersonal context.22
Related resources
- Toastmasters for public speaking. http://www.toastmasters.com
- Anxiety Disorders Association of America. http://www.adaa.org
- Social Anxiety Association. http://www.socialphobia.org
Drug brand names
- Atenolol • Tenormin
- Clonazepam • Klonopin
- Lorazepam • Ativan
- Nadolol • Corgard
- Propranolol • Inderal
Disclosure
Dr. Kelly reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Saveanu receives research support from Pfizer Inc. and is a consultant and speaker for Pfizer Inc. and GlaxoSmithKline.
1. Salmon PG. A psychological perspective on musical performance anxiety: a review of the literature. Med Prob Perform Artists 1900;51(1):2-11.
2. Beatty M. Situational and predispositional correlates of public speaking anxiety. Commun Ed 1998;37:28-39.
3. Ollendick TH, Hirshfeld-Becker DR. The developmental psychopathology of social anxiety disorder. Biol Psychiatry 2002;51(1):44-58.
4. Harris SR, Kemmerling RL, North MM. Brief virtual reality therapy for public speaking anxiety. Cyberpsychol Behav 2002;5(6):543-50.
5. Rafferty BD, Smith RE, Ptacek JT. Facilitating and debilitating trait anxiety, situational anxiety, and coping with an anticipated stressor: a process analysis. J Pers Soc Psychol 1997;72:892-906.
6. Yerkes RM, Dodson JD. The relation of strength of stimulus to rapidity of habit formation. J Comp Neurol Psychol 1908;18:459-482.
7. Hardy L, Parfitt G. A catastrophic model of anxiety and performance. Br J Psychol 1991;82:163-78.
8. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51(1):8-19.
9. Powell D. Treating individuals with debilitating performance anxiety: an introduction. J Clin Psychol 2004;60(8):801-8.
10. Merritt L, Richards A, Davis P. Performance anxiety: loss of the spoken edge. J Voice 2001;15(2):257-69.
11. Heimberg RG. Cognitive-behavioral therapy for social anxiety disorder: current status and future directions. Biol Psychiatry 2002;51:101-8.
12. Brown TA, Barlow DH. Comorbidities among anxiety disorders: implications for treatment and DSM-IV. J Consult Clin Psychol 1992;60(6):835-44.
13. Schneier FR, Johnson J, Hornig CD, et al. Social phobia: comorbidity and morbidity in an epidemiologic sample. Arch Gen Psychiatry 1992;49:282-8.
14. Abrams K, Kushner M, Medina K, Voight A. Self-administration of alcohol before and after a public speaking challenge by individuals with social phobias. Psychol Addict Behav 2002;16(1):121-8.
15. Maran AGD. Performing arts medicine. Br J Sports Med 1998;32(1):5.-
16. Bruce TJ, Saeed SA. Social anxiety disorder: a common, underrecognized mental disorder. Am Fam Physician 1999;60(8):2311-22.
17. Ostwald PF, Baron BC, Byl NM, Wilson FR. Performing arts medicine. West J Med 1994;160:48-52.
18. Slomka J. Playing with propranolol. Hastings Cent Rep 1992;22(4):13-18.
19. Blanco C, Antia SX, Liebowitz MR. Pharmacotherapy of social anxiety disorder. Biol Psychiatry 2002;51:109-20.
20. Rodebaugh TL, Chambless DL. Cognitive therapy for performance anxiety. J Clin Psychol 2004;60(8):809-20.
21. Birk L. Pharmacotherapy for performance anxiety disorders: occasionally useful but typically contraindicated. J Clin Psychol: In Session 2004;60(8):867-79.
22. Lipsitz JD, Markowitz JC, Cherry S, Fyer AJ. Open trial of interpersonal psychotherapy for the treatment of social phobia. Am J Psychiatry 1999;156(11):1814-6.
The violin is slippery in my grasp. I hear the thud of my foot tapping, but the tempo feels wrong. I’m aware of my chest pounding, a lump in my throat, and heat rising from my face. Everyone is watching me, waiting for me to make a mistake.
Why can’t I stop my hand from trembling? I can only watch as the bow jumps noisily across the strings. I should have practiced more. My mind goes blank, and I miss the page turn.
Silence. I blink, and the lights blind me as the applause comes, thankfully, and I exhale and run off the stage as the curtain closes.
Well-known performing artists—Sir Laurence Olivier, Kim Basinger, Peter O’Toole, Richard Burton, Barbra Streisand, and Luciano Pavarotti —have described bouts with acute stage fright. Performance anxiety can occur with acting, singing, or playing a musical instrument, and with nonartistic performances such as public speaking, oral examinations, competing in sporting events, sexual activity, using public restrooms, or being watched while doing a task such as surgery, eating, or writing.2
Like social phobia, performance anxiety probably develops in accomplished artists and not-so-famous individuals because of a mélange of genetic factors, innate temperament, parental influences, conditioning events, and cognitive influences.3
NORMAL VS. ABNORMAL FEAR
Performance anxiety is characterized by persisting, distressful apprehension about—or actual impairment of—performance skills to a degree unwarranted by the individual’s aptitude, training, and preparation.1 Not all performance anxiety qualifies as a mental disorder; for example, though 85% of the population experiences discomfort about public speaking,4 this anxiety does not impair most people’s ability to function.
Mild to moderate anxiety is normal and motivating in performances.5 However, anxiety’s effect on performance does not follow a bell-shaped curve, wherein moderate anxiety promotes optimal performance.6 Instead, a catastrophic model is more accurate: increasing anxiety is helpful until a certain threshold is reached, then performance plunges.7
Diagnostic criteria. DSM-IV-TR describes performance anxiety as a form of social phobia (or social anxiety disorder) characterized by marked and persistent fear of social or performance situations in which embarrassment or humiliation might occur. Approximately 13% of adults experience social phobia,8 and about 2% suffer from severe discrete performance anxiety.9
Performance anxiety does not completely overlap with social phobia, however. Test-taking anxiety and writer’s block, which can occur in a nonpublic context, do not fit neatly into the social phobia category.2 Thus, some performance anxiety forms are better grouped as another type of anxiety disorder, such as specific phobia (Figure).
Figure Performance anxiety features overlap with other anxieties
Performance anxiety is not easy to categorize. It is situational anxiety that occurs in a public context and overlaps with but does not entirely match diagnostic criteria for specific phobia, social anxiety, or panic disorder and generalized anxiety.
DIFFERENTIAL DIAGNOSIS
Social anxiety? Ask the patient about all situations that provoke anxiety to differentiate between:
- discrete performance anxiety (1 or 2 performance situations that provoke anxiety)
- and generalized social anxiety (3 or more situations that provoke anxiety).9
Individuals with “trait” anxiety may exhibit innate shyness and are considered to have generalized social phobia. Those with “state” anxiety experience anxiety in specific situations or circumstances and are more aptly described as having discrete performance anxiety.10 Whereas persons with social phobia may avoid the feared activity without inner conflict, those with performance anxiety are committed to performing the activity and are distressed when unable to perform.9
Specific phobia? A specific phobia is a circumscribed fear of a specific object, situation, or activity from which a grim outcome is feared. Specific phobia usually has no performance aspect or fear of embarrassment or failure.
Some clinicians consider certain performance anxieties—such as writer’s block, test-taking anxiety, paruresis, and even fear about sexual performance—to be specific phobias. Because performance anxieties and phobias share some cognitive and behavioral components, their treatments are similar and use of medication is controversial.
General medical condition? Perform or refer the patient for a thorough medical evaluation before you diagnose performance anxiety, as endocrine, cardiovascular, respiratory, and circulatory abnormalities can mimic or exacerbate anxiety disorders. Also consider substance abuse or withdrawal as possible causes of anxiety.
PATIENT EVALUATION
Family history. Individuals with social anxiety often report a family history of generalized social anxiety, panic disorder, or major depressive disorder.3 Similar findings seem plausible for persons with discrete performance anxiety, although comparable family history data have not been reported.
Cognitive symptoms. Four cognitive distortions are common in persons with social phobia (Table 1).11 These negative thoughts are presumably the same for performance anxiety, at least when it is a sub-type of social phobia.
Somatic symptoms. Persons with performance anxiety tend to have heightened awareness of hyperadrenergic arousal symptoms (Table 2), sometimes in all body systems. Symptoms may resemble those of a panic attack.
Behavioral symptoms. Behavioral symptoms include stuttering, mumbling, trembling voice, yawning, biting nails or lips, gritting jaw, poor eye contact, shuffling or tapping feet, unnatural or rigid postures or movements, warming up too fast or too slowly, wearing excessive makeup, or smiling abnormally. A performer may forget to carry out a routine task such as blinking, moistening lips, or turning a page of music.
These behaviors may perpetuate and reinforce anxiety by eliciting negative reactions from an audience and fulfilling the performer’s pessimistic expectations. The therapist can identify these maladaptive behaviors and target them for treatment.
Table 1
4 cognitive distortions that underlie performance anxiety
|
Table 2
Somatic symptoms of performance anxiety
| Bodily system | Symptoms |
|---|---|
| Autonomic | Blushing, diaphoresis, dry mouth |
| GI, urologic | Urinary or bowel urgency, GI discomfort |
| Cardiovascular | Tachycardia, palpitations |
| Neuromuscular | Muscle tension, tremor, paralysis |
PSYCHIATRIC COMORBIDITY
About one-third of individuals with performance anxiety have psychiatric comorbidities.9 Most common are other anxiety disorders, specifically the generalized form of social phobia, generalized anxiety disorder, panic disorder, or specific phobia.12 Mood disorders are less common. We also recommend monitoring for eating disorders because some performing artists are driven to maintain high physical appearance standards.
Personality disorder comorbidities with performance anxiety have not been studied. Some experts believe that avoidant personality and social phobia are the same conditions expressed to varying degrees on a continuum.13 Other personality disorders to consider include schizoid, paranoid, and obsessive-compulsive personalities.
Alcohol and substance use disorders are highly comorbid with performance anxiety. Alcohol use decreases public speaking anxiety,14 and approximately 6% of orchestral musicians use alcohol before a performance.15 For comparison, approximately 16% of patients who present for treatment of generalized anxiety disorder abuse alcohol, often as an attempt to self-medicate.16
TREATMENT PLANNING
Just as performance anxiety’s diagnostic classification may vary, so may treatment. Pharmacologic interventions and psychotherapy for social and specific phobias are similar. Some clinicians favor a multimodal approach addressing behavior, affect, sensation, imagery, cognition, interpersonal relationships, and biological factors.9
The performing arts community is competitive, and individuals may have differing standards about what treatments are acceptable. Some may view using medications as “cheating” or an admission of professional failure. A performer may feel medication gives an unfair advantage, that respect would be lost if others found out, or that taking medication before performing is similar to steroid use by athletes.17,18
Medication vs. psychotherapy. Medication can help diminish anxiety’s physical symptoms, but certain psychotherapies rely on these somatic symptoms for effective treatment and extinguishing of responses. Concurrent use of medications and psychotherapy for social phobia is common in everyday practice, although some studies find the combination no more effective than either treatment alone.11 Symptoms appear less likely to return after cognitive-behavioral therapy (CBT) ends than after medication is discontinued.16
Discuss treatment options with the patient. A patient who feels unable to perform without medication may develop psychological dependency. Conversely, a patient may not be able to afford the full course of psychotherapy needed for positive results. For performing artists, longer visits that incorporate medication management with psychotherapy may be more successful than brief, symptom-targeted visits.
MEDICATION MANAGEMENT
All medication use for performance anxiety is off-label. The most common choices are short-acting agents such as beta blockers or benzodiazepines (Table 3).
Table 3
Medications used to treat performance anxiety*
| Medication | Typical dosage | Possible side effects |
|---|---|---|
| Beta blockers | Medical: sedation, fatigue, dizziness, ataxia, nausea, sexual dysfunction Psychiatric:insomnia, nightmares, depression Contraindications: heart failure, bradycardia, breathing difficulties, hypotension | |
| Propranolol | 10 to 40 mg | |
| Nadolol | 20 to 120 mg | |
| Atenolol | 50 to 100 mg | |
| Benzodiazepines | Performance decrement, amnesia, sedation, discontinuation symptoms, tolerance, abuse potential | |
| Clonazepam | 0.25 to 0.5 mg | |
| Lorazepam | 0.5 to 1 mg | |
| * Off-label use; taken as-needed approximately 1 hour before performance | ||
Beta blockers can relieve autonomic and somatic symptoms such as tachycardia, tremor, and stuttering when used in low doses as needed for mild to moderate circumscribed performance anxiety.16,19 Propranolol, 10 mg about 1 hour before the performance, is most often prescribed.
Before prescribing a beta blocker, evaluate the patient’s medical history and cardiovascular status, including blood pressure and pulse. Have the patient try a test dose before the first live performance to check for side effects and tolerability (Table 3).16,19
Benzodiazepines have been used to treat social anxiety, but controlled studies have not reliably addressed their efficacy in performance anxiety. Advise the patient to abstain from alcohol when taking these medications (Table 3).
PSYCHOTHERAPY OPTIONS
CBT with components of exposure and retraining can ameliorate performance anxiety.10,20
Many performers forgo normal childhood social experiences to hone their talents, at times sacrificing sound coping skills.17 CBT’s goal is to help them reduce negative biases and restructure cognitive processes to function better at whatever task is at hand. This involves teaching them to:
- recognize pessimistic thoughts that occur before, during, and after performances
- challenge the accuracy of these thoughts
- replace them with rational, helpful thoughts based on the assimilated information.11
Exposure therapy can help individuals face feared activities so that counter-conditioning through habituation and extinction can safely occur. Useful strategies include imagination, role play, confrontation, videotaping, and homework assignments.11
Experiencing anxiety is a component of exposure therapy. Thus, some clinicians avoid using concomitant medication that might decrease anxiety’s physical symptoms and interfere with the exposure process.21
Relaxation training can help the patient recognize and respond to autonomic and physical arousal during a performance.11 For example, progressive muscle relaxation can be practiced first in session and then as homework.
Social skills training can help patients identify and change anxiety behaviors that cause negative audience reactions. Tools to help direct the patient towards more appropriate behaviors include modeling, behavior rehearsal, corrective feedback, social reinforcement, and homework assignments such as videotaping performances.11 For public speaking anxiety, vocal and physical skills training10 and computerized virtual reality courses can help.4
Interpersonal therapy may be useful, based on the premise that performance anxiety occurs within a social and interpersonal context.22
Related resources
- Toastmasters for public speaking. http://www.toastmasters.com
- Anxiety Disorders Association of America. http://www.adaa.org
- Social Anxiety Association. http://www.socialphobia.org
Drug brand names
- Atenolol • Tenormin
- Clonazepam • Klonopin
- Lorazepam • Ativan
- Nadolol • Corgard
- Propranolol • Inderal
Disclosure
Dr. Kelly reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Saveanu receives research support from Pfizer Inc. and is a consultant and speaker for Pfizer Inc. and GlaxoSmithKline.
The violin is slippery in my grasp. I hear the thud of my foot tapping, but the tempo feels wrong. I’m aware of my chest pounding, a lump in my throat, and heat rising from my face. Everyone is watching me, waiting for me to make a mistake.
Why can’t I stop my hand from trembling? I can only watch as the bow jumps noisily across the strings. I should have practiced more. My mind goes blank, and I miss the page turn.
Silence. I blink, and the lights blind me as the applause comes, thankfully, and I exhale and run off the stage as the curtain closes.
Well-known performing artists—Sir Laurence Olivier, Kim Basinger, Peter O’Toole, Richard Burton, Barbra Streisand, and Luciano Pavarotti —have described bouts with acute stage fright. Performance anxiety can occur with acting, singing, or playing a musical instrument, and with nonartistic performances such as public speaking, oral examinations, competing in sporting events, sexual activity, using public restrooms, or being watched while doing a task such as surgery, eating, or writing.2
Like social phobia, performance anxiety probably develops in accomplished artists and not-so-famous individuals because of a mélange of genetic factors, innate temperament, parental influences, conditioning events, and cognitive influences.3
NORMAL VS. ABNORMAL FEAR
Performance anxiety is characterized by persisting, distressful apprehension about—or actual impairment of—performance skills to a degree unwarranted by the individual’s aptitude, training, and preparation.1 Not all performance anxiety qualifies as a mental disorder; for example, though 85% of the population experiences discomfort about public speaking,4 this anxiety does not impair most people’s ability to function.
Mild to moderate anxiety is normal and motivating in performances.5 However, anxiety’s effect on performance does not follow a bell-shaped curve, wherein moderate anxiety promotes optimal performance.6 Instead, a catastrophic model is more accurate: increasing anxiety is helpful until a certain threshold is reached, then performance plunges.7
Diagnostic criteria. DSM-IV-TR describes performance anxiety as a form of social phobia (or social anxiety disorder) characterized by marked and persistent fear of social or performance situations in which embarrassment or humiliation might occur. Approximately 13% of adults experience social phobia,8 and about 2% suffer from severe discrete performance anxiety.9
Performance anxiety does not completely overlap with social phobia, however. Test-taking anxiety and writer’s block, which can occur in a nonpublic context, do not fit neatly into the social phobia category.2 Thus, some performance anxiety forms are better grouped as another type of anxiety disorder, such as specific phobia (Figure).
Figure Performance anxiety features overlap with other anxieties
Performance anxiety is not easy to categorize. It is situational anxiety that occurs in a public context and overlaps with but does not entirely match diagnostic criteria for specific phobia, social anxiety, or panic disorder and generalized anxiety.
DIFFERENTIAL DIAGNOSIS
Social anxiety? Ask the patient about all situations that provoke anxiety to differentiate between:
- discrete performance anxiety (1 or 2 performance situations that provoke anxiety)
- and generalized social anxiety (3 or more situations that provoke anxiety).9
Individuals with “trait” anxiety may exhibit innate shyness and are considered to have generalized social phobia. Those with “state” anxiety experience anxiety in specific situations or circumstances and are more aptly described as having discrete performance anxiety.10 Whereas persons with social phobia may avoid the feared activity without inner conflict, those with performance anxiety are committed to performing the activity and are distressed when unable to perform.9
Specific phobia? A specific phobia is a circumscribed fear of a specific object, situation, or activity from which a grim outcome is feared. Specific phobia usually has no performance aspect or fear of embarrassment or failure.
Some clinicians consider certain performance anxieties—such as writer’s block, test-taking anxiety, paruresis, and even fear about sexual performance—to be specific phobias. Because performance anxieties and phobias share some cognitive and behavioral components, their treatments are similar and use of medication is controversial.
General medical condition? Perform or refer the patient for a thorough medical evaluation before you diagnose performance anxiety, as endocrine, cardiovascular, respiratory, and circulatory abnormalities can mimic or exacerbate anxiety disorders. Also consider substance abuse or withdrawal as possible causes of anxiety.
PATIENT EVALUATION
Family history. Individuals with social anxiety often report a family history of generalized social anxiety, panic disorder, or major depressive disorder.3 Similar findings seem plausible for persons with discrete performance anxiety, although comparable family history data have not been reported.
Cognitive symptoms. Four cognitive distortions are common in persons with social phobia (Table 1).11 These negative thoughts are presumably the same for performance anxiety, at least when it is a sub-type of social phobia.
Somatic symptoms. Persons with performance anxiety tend to have heightened awareness of hyperadrenergic arousal symptoms (Table 2), sometimes in all body systems. Symptoms may resemble those of a panic attack.
Behavioral symptoms. Behavioral symptoms include stuttering, mumbling, trembling voice, yawning, biting nails or lips, gritting jaw, poor eye contact, shuffling or tapping feet, unnatural or rigid postures or movements, warming up too fast or too slowly, wearing excessive makeup, or smiling abnormally. A performer may forget to carry out a routine task such as blinking, moistening lips, or turning a page of music.
These behaviors may perpetuate and reinforce anxiety by eliciting negative reactions from an audience and fulfilling the performer’s pessimistic expectations. The therapist can identify these maladaptive behaviors and target them for treatment.
Table 1
4 cognitive distortions that underlie performance anxiety
|
Table 2
Somatic symptoms of performance anxiety
| Bodily system | Symptoms |
|---|---|
| Autonomic | Blushing, diaphoresis, dry mouth |
| GI, urologic | Urinary or bowel urgency, GI discomfort |
| Cardiovascular | Tachycardia, palpitations |
| Neuromuscular | Muscle tension, tremor, paralysis |
PSYCHIATRIC COMORBIDITY
About one-third of individuals with performance anxiety have psychiatric comorbidities.9 Most common are other anxiety disorders, specifically the generalized form of social phobia, generalized anxiety disorder, panic disorder, or specific phobia.12 Mood disorders are less common. We also recommend monitoring for eating disorders because some performing artists are driven to maintain high physical appearance standards.
Personality disorder comorbidities with performance anxiety have not been studied. Some experts believe that avoidant personality and social phobia are the same conditions expressed to varying degrees on a continuum.13 Other personality disorders to consider include schizoid, paranoid, and obsessive-compulsive personalities.
Alcohol and substance use disorders are highly comorbid with performance anxiety. Alcohol use decreases public speaking anxiety,14 and approximately 6% of orchestral musicians use alcohol before a performance.15 For comparison, approximately 16% of patients who present for treatment of generalized anxiety disorder abuse alcohol, often as an attempt to self-medicate.16
TREATMENT PLANNING
Just as performance anxiety’s diagnostic classification may vary, so may treatment. Pharmacologic interventions and psychotherapy for social and specific phobias are similar. Some clinicians favor a multimodal approach addressing behavior, affect, sensation, imagery, cognition, interpersonal relationships, and biological factors.9
The performing arts community is competitive, and individuals may have differing standards about what treatments are acceptable. Some may view using medications as “cheating” or an admission of professional failure. A performer may feel medication gives an unfair advantage, that respect would be lost if others found out, or that taking medication before performing is similar to steroid use by athletes.17,18
Medication vs. psychotherapy. Medication can help diminish anxiety’s physical symptoms, but certain psychotherapies rely on these somatic symptoms for effective treatment and extinguishing of responses. Concurrent use of medications and psychotherapy for social phobia is common in everyday practice, although some studies find the combination no more effective than either treatment alone.11 Symptoms appear less likely to return after cognitive-behavioral therapy (CBT) ends than after medication is discontinued.16
Discuss treatment options with the patient. A patient who feels unable to perform without medication may develop psychological dependency. Conversely, a patient may not be able to afford the full course of psychotherapy needed for positive results. For performing artists, longer visits that incorporate medication management with psychotherapy may be more successful than brief, symptom-targeted visits.
MEDICATION MANAGEMENT
All medication use for performance anxiety is off-label. The most common choices are short-acting agents such as beta blockers or benzodiazepines (Table 3).
Table 3
Medications used to treat performance anxiety*
| Medication | Typical dosage | Possible side effects |
|---|---|---|
| Beta blockers | Medical: sedation, fatigue, dizziness, ataxia, nausea, sexual dysfunction Psychiatric:insomnia, nightmares, depression Contraindications: heart failure, bradycardia, breathing difficulties, hypotension | |
| Propranolol | 10 to 40 mg | |
| Nadolol | 20 to 120 mg | |
| Atenolol | 50 to 100 mg | |
| Benzodiazepines | Performance decrement, amnesia, sedation, discontinuation symptoms, tolerance, abuse potential | |
| Clonazepam | 0.25 to 0.5 mg | |
| Lorazepam | 0.5 to 1 mg | |
| * Off-label use; taken as-needed approximately 1 hour before performance | ||
Beta blockers can relieve autonomic and somatic symptoms such as tachycardia, tremor, and stuttering when used in low doses as needed for mild to moderate circumscribed performance anxiety.16,19 Propranolol, 10 mg about 1 hour before the performance, is most often prescribed.
Before prescribing a beta blocker, evaluate the patient’s medical history and cardiovascular status, including blood pressure and pulse. Have the patient try a test dose before the first live performance to check for side effects and tolerability (Table 3).16,19
Benzodiazepines have been used to treat social anxiety, but controlled studies have not reliably addressed their efficacy in performance anxiety. Advise the patient to abstain from alcohol when taking these medications (Table 3).
PSYCHOTHERAPY OPTIONS
CBT with components of exposure and retraining can ameliorate performance anxiety.10,20
Many performers forgo normal childhood social experiences to hone their talents, at times sacrificing sound coping skills.17 CBT’s goal is to help them reduce negative biases and restructure cognitive processes to function better at whatever task is at hand. This involves teaching them to:
- recognize pessimistic thoughts that occur before, during, and after performances
- challenge the accuracy of these thoughts
- replace them with rational, helpful thoughts based on the assimilated information.11
Exposure therapy can help individuals face feared activities so that counter-conditioning through habituation and extinction can safely occur. Useful strategies include imagination, role play, confrontation, videotaping, and homework assignments.11
Experiencing anxiety is a component of exposure therapy. Thus, some clinicians avoid using concomitant medication that might decrease anxiety’s physical symptoms and interfere with the exposure process.21
Relaxation training can help the patient recognize and respond to autonomic and physical arousal during a performance.11 For example, progressive muscle relaxation can be practiced first in session and then as homework.
Social skills training can help patients identify and change anxiety behaviors that cause negative audience reactions. Tools to help direct the patient towards more appropriate behaviors include modeling, behavior rehearsal, corrective feedback, social reinforcement, and homework assignments such as videotaping performances.11 For public speaking anxiety, vocal and physical skills training10 and computerized virtual reality courses can help.4
Interpersonal therapy may be useful, based on the premise that performance anxiety occurs within a social and interpersonal context.22
Related resources
- Toastmasters for public speaking. http://www.toastmasters.com
- Anxiety Disorders Association of America. http://www.adaa.org
- Social Anxiety Association. http://www.socialphobia.org
Drug brand names
- Atenolol • Tenormin
- Clonazepam • Klonopin
- Lorazepam • Ativan
- Nadolol • Corgard
- Propranolol • Inderal
Disclosure
Dr. Kelly reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Saveanu receives research support from Pfizer Inc. and is a consultant and speaker for Pfizer Inc. and GlaxoSmithKline.
1. Salmon PG. A psychological perspective on musical performance anxiety: a review of the literature. Med Prob Perform Artists 1900;51(1):2-11.
2. Beatty M. Situational and predispositional correlates of public speaking anxiety. Commun Ed 1998;37:28-39.
3. Ollendick TH, Hirshfeld-Becker DR. The developmental psychopathology of social anxiety disorder. Biol Psychiatry 2002;51(1):44-58.
4. Harris SR, Kemmerling RL, North MM. Brief virtual reality therapy for public speaking anxiety. Cyberpsychol Behav 2002;5(6):543-50.
5. Rafferty BD, Smith RE, Ptacek JT. Facilitating and debilitating trait anxiety, situational anxiety, and coping with an anticipated stressor: a process analysis. J Pers Soc Psychol 1997;72:892-906.
6. Yerkes RM, Dodson JD. The relation of strength of stimulus to rapidity of habit formation. J Comp Neurol Psychol 1908;18:459-482.
7. Hardy L, Parfitt G. A catastrophic model of anxiety and performance. Br J Psychol 1991;82:163-78.
8. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51(1):8-19.
9. Powell D. Treating individuals with debilitating performance anxiety: an introduction. J Clin Psychol 2004;60(8):801-8.
10. Merritt L, Richards A, Davis P. Performance anxiety: loss of the spoken edge. J Voice 2001;15(2):257-69.
11. Heimberg RG. Cognitive-behavioral therapy for social anxiety disorder: current status and future directions. Biol Psychiatry 2002;51:101-8.
12. Brown TA, Barlow DH. Comorbidities among anxiety disorders: implications for treatment and DSM-IV. J Consult Clin Psychol 1992;60(6):835-44.
13. Schneier FR, Johnson J, Hornig CD, et al. Social phobia: comorbidity and morbidity in an epidemiologic sample. Arch Gen Psychiatry 1992;49:282-8.
14. Abrams K, Kushner M, Medina K, Voight A. Self-administration of alcohol before and after a public speaking challenge by individuals with social phobias. Psychol Addict Behav 2002;16(1):121-8.
15. Maran AGD. Performing arts medicine. Br J Sports Med 1998;32(1):5.-
16. Bruce TJ, Saeed SA. Social anxiety disorder: a common, underrecognized mental disorder. Am Fam Physician 1999;60(8):2311-22.
17. Ostwald PF, Baron BC, Byl NM, Wilson FR. Performing arts medicine. West J Med 1994;160:48-52.
18. Slomka J. Playing with propranolol. Hastings Cent Rep 1992;22(4):13-18.
19. Blanco C, Antia SX, Liebowitz MR. Pharmacotherapy of social anxiety disorder. Biol Psychiatry 2002;51:109-20.
20. Rodebaugh TL, Chambless DL. Cognitive therapy for performance anxiety. J Clin Psychol 2004;60(8):809-20.
21. Birk L. Pharmacotherapy for performance anxiety disorders: occasionally useful but typically contraindicated. J Clin Psychol: In Session 2004;60(8):867-79.
22. Lipsitz JD, Markowitz JC, Cherry S, Fyer AJ. Open trial of interpersonal psychotherapy for the treatment of social phobia. Am J Psychiatry 1999;156(11):1814-6.
1. Salmon PG. A psychological perspective on musical performance anxiety: a review of the literature. Med Prob Perform Artists 1900;51(1):2-11.
2. Beatty M. Situational and predispositional correlates of public speaking anxiety. Commun Ed 1998;37:28-39.
3. Ollendick TH, Hirshfeld-Becker DR. The developmental psychopathology of social anxiety disorder. Biol Psychiatry 2002;51(1):44-58.
4. Harris SR, Kemmerling RL, North MM. Brief virtual reality therapy for public speaking anxiety. Cyberpsychol Behav 2002;5(6):543-50.
5. Rafferty BD, Smith RE, Ptacek JT. Facilitating and debilitating trait anxiety, situational anxiety, and coping with an anticipated stressor: a process analysis. J Pers Soc Psychol 1997;72:892-906.
6. Yerkes RM, Dodson JD. The relation of strength of stimulus to rapidity of habit formation. J Comp Neurol Psychol 1908;18:459-482.
7. Hardy L, Parfitt G. A catastrophic model of anxiety and performance. Br J Psychol 1991;82:163-78.
8. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51(1):8-19.
9. Powell D. Treating individuals with debilitating performance anxiety: an introduction. J Clin Psychol 2004;60(8):801-8.
10. Merritt L, Richards A, Davis P. Performance anxiety: loss of the spoken edge. J Voice 2001;15(2):257-69.
11. Heimberg RG. Cognitive-behavioral therapy for social anxiety disorder: current status and future directions. Biol Psychiatry 2002;51:101-8.
12. Brown TA, Barlow DH. Comorbidities among anxiety disorders: implications for treatment and DSM-IV. J Consult Clin Psychol 1992;60(6):835-44.
13. Schneier FR, Johnson J, Hornig CD, et al. Social phobia: comorbidity and morbidity in an epidemiologic sample. Arch Gen Psychiatry 1992;49:282-8.
14. Abrams K, Kushner M, Medina K, Voight A. Self-administration of alcohol before and after a public speaking challenge by individuals with social phobias. Psychol Addict Behav 2002;16(1):121-8.
15. Maran AGD. Performing arts medicine. Br J Sports Med 1998;32(1):5.-
16. Bruce TJ, Saeed SA. Social anxiety disorder: a common, underrecognized mental disorder. Am Fam Physician 1999;60(8):2311-22.
17. Ostwald PF, Baron BC, Byl NM, Wilson FR. Performing arts medicine. West J Med 1994;160:48-52.
18. Slomka J. Playing with propranolol. Hastings Cent Rep 1992;22(4):13-18.
19. Blanco C, Antia SX, Liebowitz MR. Pharmacotherapy of social anxiety disorder. Biol Psychiatry 2002;51:109-20.
20. Rodebaugh TL, Chambless DL. Cognitive therapy for performance anxiety. J Clin Psychol 2004;60(8):809-20.
21. Birk L. Pharmacotherapy for performance anxiety disorders: occasionally useful but typically contraindicated. J Clin Psychol: In Session 2004;60(8):867-79.
22. Lipsitz JD, Markowitz JC, Cherry S, Fyer AJ. Open trial of interpersonal psychotherapy for the treatment of social phobia. Am J Psychiatry 1999;156(11):1814-6.
Drug-drug interactions: Avoid serious adverse events with mood stabilizers
Drug-drug interactions (DDIs) can be viewed as physiologic combat wherein a “perpetrator” drug affects a “victim” drug’s pharmacokinetics or pharmacodynamics. Your challenge is to deter that interaction in patients taking two or more medications.
This article—first in a series—discusses polypharmacy risk factors that increase the likelihood of detrimental DDIs, then focuses on DDIs in patients taking mood stabilizers for bipolar disorder. We also offer practical tips to reduce DDI risk. Future articles will discuss DDI risks with antidepressants, antipsychotics, and anxiolytics.
To predict DDIs, you need to know psychotropics’ mechanism of action, metabolism, and effects on cytochrome P-450 (CYP) enzymes. Our discussion is not exhaustive because the data base is massive and new interactions continue to be discovered. Our aim is to equip you to anticipate and prevent DDIs when prescribing.
WHAT ARE ADVERSE DDIs?
An adverse event (AE) is any undesirable experience that occurs when a patient uses a medical product, whether or not the product caused the event. The FDA says an “undesirable experience” may be:
- an unfavorable and unintended symptom or sign
- an abnormal lab or radiographic finding
- a disease that is temporarily associated with the medical product.
An AE becomes “serious” (an SAE) when its duration, intensity, and/or frequency leads to death, a life-threatening condition, initial or prolonged hospitalization, disability, or congenital anomaly. Reporting is voluntary, but we strongly recommend that you report all SAEs to the FDA.
These definitions can help you confirm that a patient has experienced an SAE, but the task becomes more complicated when you try to attribute an SAE to a drug interaction. In the absence of an FDA definition, we assert that DDIs are responsible for SAEs when a perpetrator drug affects the pharmacokinetics or pharmacodynamics of a victim drug and exacerbates a known untoward event of the victim drug (Box 1).1-5 Which drug is the perpetrator and which is the victim is not always clear, and sometimes a medication—such as carbamazepine—can be both at once.
More than 100,000 possible detrimental DDIs have been documented in medical literature and pharmaceutical company data. This number is likely to grow with increased scrutiny, as
DDIs cause morbidity, mortality, and increased health care costs. More than 106,000 Americans die each year from properly prescribed, correctly taken medications. Polypharmacy is associated with extended hospital stays, and using >6 drugs is an independent predictor of death. DDIs contribute to the cause of death in acute overdoses and can be responsible for false-positive suicide diagnoses.
In clinical practice, DDI-associated toxicity may be mistaken for a new disease process, or a disease may be incorrectly perceived as progressing when a medication is rendered ineffective.
Source: References 1-5
RISKS OF POLYPHARMACY
Individuals with psychiatric illnesses are at particular risk for DDIs (Box 2). Patients seen by psychiatrists, for example, are six times more likely than patients seen by primary care physicians to be taking multiple medications.6
Polypharmacy increases the risk of adverse events, nonadherence, medication errors, and drug interactions.7 FDA’s MedWatch Web site lists more than 630 DDI warnings.8 The more medications a patient is taking, the greater the risk for detrimental DDIs and cumulative toxicity,9 which often lead to DDI-induced AEs.10
A study of DDIs in 5,125 mostly older outpatients11 found that:
- 1,594 (31%) had at least one interacting drug combination (average 1.6)
- subjects with one or more DDIs were taking an average 8.1 drugs, compared with 5.2 drugs in those without DDIs—a significant difference
- 155 (3%) had interactions of “major clinical significance.”
- Although drug interactions are responsible for only 3.8% of emergency department visits, patients with DDIs are usually admitted to the hospital.13
- Preventable drug interactions cause approximately one-third of all AEs in hospitalized patients and account for one-half of all AE costs.14
Symptom-based prescribing. Patients with psychiatric illness are often prescribed >1 medication to manage symptoms and signs, rather than a single medication targeting a specific psychiatric disorder.
Multiple prescribers. Patients with anxiety and depressive disorders may see multiple providers, which increases the risk for polypharmacy, drug-drug interactions, and adverse events.
Medical comorbidity. Persons with psychiatric illness are at increased risk for concomitant medical illness, and persons with medical illness are at increased risk for psychiatric illness.
Psychiatric comorbidity. Persons with one psychiatric illness are at increased risk for other psychiatric illnesses.
Source: Adapted from reference 6.
HOW TO MINIMIZE DDI RISK
Use the acronym “LISTEN” (Table 1) to minimize DDI risk in patients taking combination therapies.16 The 6 steps in LISTEN can help you determine which drug or drugs you may discontinue before adding another.
We also recommend that you monitor therapeutic and toxic effects by checking serum drug levels, especially for drugs with a low therapeutic index. Lithium, for example, requires close mentoring of plasma concentration every 2 to 6 months and during dosage adjustments to avoid toxicity.17 Therapeutic drug monitoring has been shown to prevent adverse events from DDIs.16 For added safety, encourage patents to purchase all medications at one pharmacy and to enroll in that pharmacy’s DDI monitoring program.18
Keep in mind that systemic conditions may require a dosage change:
- Increased volume of distribution, as in patients who gain weight or total water volume, requires higher doses to maintain a constant therapeutic effect.
- Reduced clearance, as in patients with decreased renal or hepatic function, will likely require lower doses to prevent toxicity.19
LISTEN: 6 tips to minimize DDI risk
| L | Listeach drug’s name and dosage in the patient’s chart and in a note given to the patient. |
| I | Each drug should have a clear indication and well-defined therapeutic goal; discontinue any drug not achieving its goal |
| S | Make the regimen as simple as possible, with once- or twice-daily dosing. |
| T | When possible, treat multiple symptoms with a single drug, rather than multiple symptoms with multiple drugs |
| E | Educatepatients about polypharmacy, DDIs, and adverse events; assess all medications—including vitamins, minerals, herbs, dietary supplements, nonprescription products—and address potential DDIs |
| N | Avoid prescribing medications with a narrow therapeutic window. |
DDIsWITH MOOD STABILIZERS
Diagnoses of schizophrenia, anxiety disorders, and affective disorders are major risk factors for polypharmacy.20 DDIs are a particular concern in patients with bipolar disorder, given their complex treatment regimens.21
Interactions occur with the most commonly prescribed bipolar medications, including lithium and anticonvulsants (Table 2).17.21-25 Although atypical antipsychotics are also considered mood stabilizers in bipolar disorder, we will discuss their potential DDIs in a future article.
Table 2
Some drug-drug interactions with mood stabilizers
| Mood stabilizer | Drug interactions |
|---|---|
| Carbamazepine | ↑plasma clomipramine, phenytoin, primidone |
| ↑risk of neurotoxic side effects and confusional states with lithium | |
| Alters thyroid function with anticonvulsants | |
| ↓anticoagulant concentrations and↑bleeding risk | |
| ↓oral contraceptive reliability; can cause false-negative pregnancy tests | |
| ↑metabolism and may ↓efficacy of cancer chemotherapy (docetaxel, estrogens, paclitaxel, progesterone, cyclophosphamide) | |
| ↑aprepitant, granisetron metabolism and ↓efficacy | |
| ↑glipizide, tolbutamide metabolism | |
| Lithium | NSAIDs (ibuprofen, indomethacin, piroxicam) and COX-2 inhibitors ↑plasma lithium |
| ACE inhibitors ↑plasma lithium | |
| Calcium channel blockers and carbamazepine ↑lithium neurotoxicity | |
| SSRIs ↑diarrhea, confusion, tremor, dizziness, and agitation | |
| Acetazolamide, urea, xanthine preparations, alkalinizing agents such as sodium bicarbonate ↓plasma lithium | |
| Metronidazole ↑lithium toxicity | |
| Encephalopathic syndrome possible with haloperidol | |
| Lamotrigine | ↑concentration of carbamazepine’s epoxide metabolite |
| Carbamazepine, phenytoin, phenobarbital ↓plasma lamotrigine 40% to 50% | |
| ↑plasma sertraline | |
| ↓plasma valproic acid 25%; valproic acid doubles plasma lamotrigine and ↑rash risk | |
| Topiramate | ↑valproic acid concentrations 11%; valproic acid ↓plasma topiramate 14% |
| ↑plasma phenytoin up to 25%; phenytoin, carbamazepine ↓plasma topiramate by 40% to 48% | |
| ↓digoxin bioavailability | |
| ↓oral contraceptive efficacy | |
| Valproic acid | ↑plasma phenobarbital, primidone |
| ↓phenytoin clearance, volume distribution and ↑breakthrough seizure risk | |
| ↑serum concentration of antiepileptics, such as lamotrigine; absence status possible with clonazepam | |
| ↑= Increases ↓= Decreases | |
| ACE = angiotensin-converting enzyme; COX = cyclooxygenase | |
| NSAIDs = nonsteroidal anti-inflammatory drugs; SSRIs = selective serotonin reuptake inhibitors | |
| Source: References 17, 21-25 | |
LITHIUM: TOXICITY RISK
Lithium is excreted via the kidneys, so be cautious when using lithium in patients taking diuretics.17,22 Drugs that can lower serum lithium concentrations by increasing urinary lithium excretion include acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate.17
Combining lithium with selective serotonin reuptake inhibitors can cause diarrhea, confusion, tremor, dizziness, and agitation.17 An encephalopathic syndrome has occurred in a few patients treated with lithium plus haloperidol.
Monitor lithium levels closely when bipolar patients start or stop nonsteroidal anti-inflammatory drugs (NSAIDs). Nonprescription ibuprofen can cause serious and even life-threatening serum lithium elevations by affecting lithium’s rate of tubular reabsorption.26 Indomethacin, piroxicam, and selective cyclooxygenase-2 (COX-2) inhibitors also increase plasma lithium concentrations.25
For patients taking lithium with heart drugs, angiotensin-converting enzyme (ACE) inhibitors may increase plasma lithium levels,17 and calcium channel blockers may increase the neurotoxicity risk.17,22 Using the anti-infective metronidazole with lithium may provoke lithium toxicity.
VALPROIC ACID: MONITOR CLEARANCE
Drugs that affect the expression of hepatic enzymes—especially glucuronosyltransferase—may increase clearance of valproic acid and its derivatives. Phenytoin, carbamazepine, or phenobarbital, for example, can double valproic acid clearance.
On the other hand, drugs that inhibit CYP-450 (such as antidepressants) have little effect on valproic acid concentration. Valproate can decrease plasma clearance of amitriptyline, so consider monitoring this tricyclic’s blood levels in patients also taking valproate.17
Because valproic acid can increase serum phenobarbital, monitor barbiturate concentrations when using these two drugs. A similar interaction occurs with primidone, which is metabolized into a barbiturate. Breakthrough seizures may occur with phenytoin, as valproic acid can reduce phenytoin clearance and apparent volume distribution by 25%.22
Using valproic acid with clonazepam may produce absence status in patients with a history of absence-type seizures.17 Valproic acid also displaces diazepam from its plasma albumin binding sites and inhibits its metabolism.
Concomitant use of valproic acid can increase serum concentrations of other antiepileptic drugs. For example, lamotrigine levels may double,24 and felbamate’s peak concentration may increase and require dosage reduction. Valproic acid may also interact with nonpsychiatric medications:
- Subtherapeutic valproic acid levels have been reported when co-administered with the antibiotic meropenem.
- In patients with HIV infection, valproic acid can decrease clearance of the antiretroviral zidovudine by 38%.
- Patients receiving rifampin for tuberculosis may need a dosage adjustment, as oral rifampin’s clearance can increase 40% with concomitant valproic acid.
CARBAMAZEPINE: SELF-INDUCER
Metabolized by CYP 3A4, carbamazepine may induce its own metabolism as well as the CYP 3A4 isoenzyme. Therefore inhibitors and inducers of CYP 3A4 may affect carbamazepine plasma levels.
Carbamazepine can increase plasma levels of other psychotropics including clomipramine, phenytoin, and primidone.17,22 When used with lithium, it may increase the risk of neurotoxic side effects and confusion.23 It can alter thyroid function when used with other anticonvulsants.
For bipolar patients with diabetes, carbamazepine can cause hyperglycemia by inducing the metabolism of oral sulfonylureas such as glipizide and tolbutamide. In women, carbamazepine decreases the reliability of oral contraceptives17 and can cause false-negative pregnancy tests.24
For cancer patients, concurrent carbamazepine may induce metabolism of chemotherapy drugs such as docetaxel, estrogens, paclitaxel, progesterone, and cyclophosphamide, decreasing their efficacy.21 It can increase metabolism of aprepitant and granisetron—used to treat chemotherapy-related nausea—reducing plasma concentrations and possibly efficacy. Carbamazepine’s additive dopamine blockade can increase the risk of extrapyramidal symptoms when used with docetaxel or the antiemetic/antivertigo agents chlorpromazine, metoclopramide, or prochlorperazine.
Carbamazepine increases elimination of some cardiovascular drugs and may decrease the effect of antiarrhythmics such as lidocaine and quinidine; calcium channel blockers such as amlodipine, nifedipine, felodipine, nisoldipine, diltiazem, and verapamil; the beta blocker propranolol; and the vasodilator bosetan.21 Carbamazepine also reduces anticoagulant concentrations, and breakthrough bleeding has been reported.
(See "Out of the Pipeline−extended−release carbamazepine" for a listing of drugs that interact with this agent.)
OTHER ANTICONVULSANTS
Lamotrigine. Some concomitant CNS medications—such as carbamazepine, phenytoin or phenobarbital—reduce lamotrigine serum concentrations by as much as 50%.17 This substantial reduction may give the impression that the patient is not responding to therapeutic lamotrigine doses.
Patients taking lamotrigine with carbamazepine may be at greater risk for dizziness, diplopia, ataxia, and blurred vision because of increased serum concentration of carbamazepine’s epoxide metabolite. Valproic acid doubles lamotrigine serum concentration and increases the risk of rash, whereas lamotrigine decreases valproic acid concentration by 25%.17 Lamotrigine’s manufacturer offers special starting kits for patients taking carbamazepine or valproic acid.
Sertraline increases plasma lamotrigine concentration—but to a lesser extent than does valproic acid17 —and no dosage adjustment is needed.
Topiramate. Concomitant carbamazepine or phenytoin reduces topiramate concentration by 40% to 48%, whereas topiramate increases phenytoin concentration up to 25%. Similarly, valproic acid reduces topiramate’s concentration by 14%, while at the same time valproic acid concentration increases by 11%.17
Topiramate slightly decreases digoxin’s bioavailability and the efficacy of estrogenic oral contraceptives.17,22
Related resources
- Cytochrome P-450 interaction checker. www.drug-interaction.com.
- FDA-reported drug-drug interactions. http://vm.cfsan.fda.gov/~lrd/fdinter.html.
- Psychiatric drug interactions. www.preskorn.com.
- FDA definitions Adverse event: http://www.fda.gov/cder/guidance/iche2a.pdf. Serious adverse event: http://www.fda.gov/medwatch/report/DESK/advevnt.htm.
- Aprepitant • Emend
- Bosentan • Tracleer
- Carbamazepine • Tegretol, others
- Chlorpromazine • Thorazine
- Clomipramine • Anafranil, others
- Clonazepam • Klonopin
- Cyclophosphamide • Cytoxan, Neosar
- Diazepam • Valium
- Diltiazem • Cardizem, others
- Docetaxel • Taxotere
- Felbamate • Felbatol
- Felodipine • Plendil
- Granisetron • Kytril
- Glipizide • Glucotrol
- Haloperidol • Haldol
- Indomethacin • Indocin
- Lamotrigine • Lamictal
- Meropenem • Merrem
- Metoclopramide • Reglan
- Metronidazole • Flagyl
- Nifedipine • Adalat, Procardia
- Nisoldipine • Sular
- Paclitaxel • Taxol, others
- Phenobarbital • Solfoton
- Phenytoin • Dilantin
- Piroxicam • Feldene
- Primidone • Mysoline
- Prochlorperazine • Compazine
- Propranolol • Inderal
- Rifampin • Rifadin
- Sertraline • Zoloft
- Tolbutamide • Orinase
- Topiramate • Topamax
- Valproic acid • Depakote
- Verapamil • Calan, others
- Zidovudine • Retrovir
Dr. Ramadan and Dr. Werder report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Preskorn has received grants or has been a consultant or speaker for Abbott Laboratories, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb Co., Merck & Co., Eisai Inc., Eli Lilly and Co., GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson, Novartis Pharmaceuticals, Organon, Otsuka America Pharmaceutical Inc., Pfizer Inc., Solvay Pharmaceuticals, Sanofi-Aventis, and Wyeth.
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17. Physicians’ Desk Reference (59th ed). Montvale, NJ: Thomson PDR; 2005.
18. Sandson NB. Exploring drug interaction in psychiatry. Psychiatric times 2004;May:42-8.
19. Todi SK, Hartmann RA. Pharmacologic principles. In: Civetta JM, Taylor RW, Kirby RR, (eds). Critical care (3rd ed). Philadelphia: Lippincott-Raven Publishers; 1997;485-8.
20. Shapiro LE, Shear NH. Drug interactions: Proteins, pumps, and P-450s. J Am Acad Dermatol 2002;47:467-84.
21. Keck PE, Jr, Dewan N, Nasrallah HA. Bipolar disorder: the clinician’s guide to pharmacotherapy for patients with co-occurring medical conditions. Current Psychiatry 2005;4(Feb)(suppl):1-51.
22. Sadock BJ, Sadock VA. Kaplan and Sadock’s pocket handbook of psychiatric drug treatment (3rd ed). Philadelphia: Lippincott Williams & Wilkins; 2001;144-5,178-83,256-7.
23. Shukla S, Godwin CD, Long LE, Miller MG. Lithium-carbamazepine neurotoxicity and risk factors. Am J Psychiatry 1984;141:1604-6.
24. Licht RW, Vestergaard P, Kessing LV, et al. Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark. Acta Psychiatr Scand Suppl 2003;(419):1-22.
25. Phelan KM, Mosholder AD, Lu S. Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs. J Clin Psychiatry 2003;64:1328-34.
26. Ragheb M, Ban TA, Buchanan D, Frolich JC. Interaction of indomethacin and ibuprofen with lithium in manic patients under steady-state lithium level. J Clin Psychiatry 1980;11:397-8.
Drug-drug interactions (DDIs) can be viewed as physiologic combat wherein a “perpetrator” drug affects a “victim” drug’s pharmacokinetics or pharmacodynamics. Your challenge is to deter that interaction in patients taking two or more medications.
This article—first in a series—discusses polypharmacy risk factors that increase the likelihood of detrimental DDIs, then focuses on DDIs in patients taking mood stabilizers for bipolar disorder. We also offer practical tips to reduce DDI risk. Future articles will discuss DDI risks with antidepressants, antipsychotics, and anxiolytics.
To predict DDIs, you need to know psychotropics’ mechanism of action, metabolism, and effects on cytochrome P-450 (CYP) enzymes. Our discussion is not exhaustive because the data base is massive and new interactions continue to be discovered. Our aim is to equip you to anticipate and prevent DDIs when prescribing.
WHAT ARE ADVERSE DDIs?
An adverse event (AE) is any undesirable experience that occurs when a patient uses a medical product, whether or not the product caused the event. The FDA says an “undesirable experience” may be:
- an unfavorable and unintended symptom or sign
- an abnormal lab or radiographic finding
- a disease that is temporarily associated with the medical product.
An AE becomes “serious” (an SAE) when its duration, intensity, and/or frequency leads to death, a life-threatening condition, initial or prolonged hospitalization, disability, or congenital anomaly. Reporting is voluntary, but we strongly recommend that you report all SAEs to the FDA.
These definitions can help you confirm that a patient has experienced an SAE, but the task becomes more complicated when you try to attribute an SAE to a drug interaction. In the absence of an FDA definition, we assert that DDIs are responsible for SAEs when a perpetrator drug affects the pharmacokinetics or pharmacodynamics of a victim drug and exacerbates a known untoward event of the victim drug (Box 1).1-5 Which drug is the perpetrator and which is the victim is not always clear, and sometimes a medication—such as carbamazepine—can be both at once.
More than 100,000 possible detrimental DDIs have been documented in medical literature and pharmaceutical company data. This number is likely to grow with increased scrutiny, as
DDIs cause morbidity, mortality, and increased health care costs. More than 106,000 Americans die each year from properly prescribed, correctly taken medications. Polypharmacy is associated with extended hospital stays, and using >6 drugs is an independent predictor of death. DDIs contribute to the cause of death in acute overdoses and can be responsible for false-positive suicide diagnoses.
In clinical practice, DDI-associated toxicity may be mistaken for a new disease process, or a disease may be incorrectly perceived as progressing when a medication is rendered ineffective.
Source: References 1-5
RISKS OF POLYPHARMACY
Individuals with psychiatric illnesses are at particular risk for DDIs (Box 2). Patients seen by psychiatrists, for example, are six times more likely than patients seen by primary care physicians to be taking multiple medications.6
Polypharmacy increases the risk of adverse events, nonadherence, medication errors, and drug interactions.7 FDA’s MedWatch Web site lists more than 630 DDI warnings.8 The more medications a patient is taking, the greater the risk for detrimental DDIs and cumulative toxicity,9 which often lead to DDI-induced AEs.10
A study of DDIs in 5,125 mostly older outpatients11 found that:
- 1,594 (31%) had at least one interacting drug combination (average 1.6)
- subjects with one or more DDIs were taking an average 8.1 drugs, compared with 5.2 drugs in those without DDIs—a significant difference
- 155 (3%) had interactions of “major clinical significance.”
- Although drug interactions are responsible for only 3.8% of emergency department visits, patients with DDIs are usually admitted to the hospital.13
- Preventable drug interactions cause approximately one-third of all AEs in hospitalized patients and account for one-half of all AE costs.14
Symptom-based prescribing. Patients with psychiatric illness are often prescribed >1 medication to manage symptoms and signs, rather than a single medication targeting a specific psychiatric disorder.
Multiple prescribers. Patients with anxiety and depressive disorders may see multiple providers, which increases the risk for polypharmacy, drug-drug interactions, and adverse events.
Medical comorbidity. Persons with psychiatric illness are at increased risk for concomitant medical illness, and persons with medical illness are at increased risk for psychiatric illness.
Psychiatric comorbidity. Persons with one psychiatric illness are at increased risk for other psychiatric illnesses.
Source: Adapted from reference 6.
HOW TO MINIMIZE DDI RISK
Use the acronym “LISTEN” (Table 1) to minimize DDI risk in patients taking combination therapies.16 The 6 steps in LISTEN can help you determine which drug or drugs you may discontinue before adding another.
We also recommend that you monitor therapeutic and toxic effects by checking serum drug levels, especially for drugs with a low therapeutic index. Lithium, for example, requires close mentoring of plasma concentration every 2 to 6 months and during dosage adjustments to avoid toxicity.17 Therapeutic drug monitoring has been shown to prevent adverse events from DDIs.16 For added safety, encourage patents to purchase all medications at one pharmacy and to enroll in that pharmacy’s DDI monitoring program.18
Keep in mind that systemic conditions may require a dosage change:
- Increased volume of distribution, as in patients who gain weight or total water volume, requires higher doses to maintain a constant therapeutic effect.
- Reduced clearance, as in patients with decreased renal or hepatic function, will likely require lower doses to prevent toxicity.19
LISTEN: 6 tips to minimize DDI risk
| L | Listeach drug’s name and dosage in the patient’s chart and in a note given to the patient. |
| I | Each drug should have a clear indication and well-defined therapeutic goal; discontinue any drug not achieving its goal |
| S | Make the regimen as simple as possible, with once- or twice-daily dosing. |
| T | When possible, treat multiple symptoms with a single drug, rather than multiple symptoms with multiple drugs |
| E | Educatepatients about polypharmacy, DDIs, and adverse events; assess all medications—including vitamins, minerals, herbs, dietary supplements, nonprescription products—and address potential DDIs |
| N | Avoid prescribing medications with a narrow therapeutic window. |
DDIsWITH MOOD STABILIZERS
Diagnoses of schizophrenia, anxiety disorders, and affective disorders are major risk factors for polypharmacy.20 DDIs are a particular concern in patients with bipolar disorder, given their complex treatment regimens.21
Interactions occur with the most commonly prescribed bipolar medications, including lithium and anticonvulsants (Table 2).17.21-25 Although atypical antipsychotics are also considered mood stabilizers in bipolar disorder, we will discuss their potential DDIs in a future article.
Table 2
Some drug-drug interactions with mood stabilizers
| Mood stabilizer | Drug interactions |
|---|---|
| Carbamazepine | ↑plasma clomipramine, phenytoin, primidone |
| ↑risk of neurotoxic side effects and confusional states with lithium | |
| Alters thyroid function with anticonvulsants | |
| ↓anticoagulant concentrations and↑bleeding risk | |
| ↓oral contraceptive reliability; can cause false-negative pregnancy tests | |
| ↑metabolism and may ↓efficacy of cancer chemotherapy (docetaxel, estrogens, paclitaxel, progesterone, cyclophosphamide) | |
| ↑aprepitant, granisetron metabolism and ↓efficacy | |
| ↑glipizide, tolbutamide metabolism | |
| Lithium | NSAIDs (ibuprofen, indomethacin, piroxicam) and COX-2 inhibitors ↑plasma lithium |
| ACE inhibitors ↑plasma lithium | |
| Calcium channel blockers and carbamazepine ↑lithium neurotoxicity | |
| SSRIs ↑diarrhea, confusion, tremor, dizziness, and agitation | |
| Acetazolamide, urea, xanthine preparations, alkalinizing agents such as sodium bicarbonate ↓plasma lithium | |
| Metronidazole ↑lithium toxicity | |
| Encephalopathic syndrome possible with haloperidol | |
| Lamotrigine | ↑concentration of carbamazepine’s epoxide metabolite |
| Carbamazepine, phenytoin, phenobarbital ↓plasma lamotrigine 40% to 50% | |
| ↑plasma sertraline | |
| ↓plasma valproic acid 25%; valproic acid doubles plasma lamotrigine and ↑rash risk | |
| Topiramate | ↑valproic acid concentrations 11%; valproic acid ↓plasma topiramate 14% |
| ↑plasma phenytoin up to 25%; phenytoin, carbamazepine ↓plasma topiramate by 40% to 48% | |
| ↓digoxin bioavailability | |
| ↓oral contraceptive efficacy | |
| Valproic acid | ↑plasma phenobarbital, primidone |
| ↓phenytoin clearance, volume distribution and ↑breakthrough seizure risk | |
| ↑serum concentration of antiepileptics, such as lamotrigine; absence status possible with clonazepam | |
| ↑= Increases ↓= Decreases | |
| ACE = angiotensin-converting enzyme; COX = cyclooxygenase | |
| NSAIDs = nonsteroidal anti-inflammatory drugs; SSRIs = selective serotonin reuptake inhibitors | |
| Source: References 17, 21-25 | |
LITHIUM: TOXICITY RISK
Lithium is excreted via the kidneys, so be cautious when using lithium in patients taking diuretics.17,22 Drugs that can lower serum lithium concentrations by increasing urinary lithium excretion include acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate.17
Combining lithium with selective serotonin reuptake inhibitors can cause diarrhea, confusion, tremor, dizziness, and agitation.17 An encephalopathic syndrome has occurred in a few patients treated with lithium plus haloperidol.
Monitor lithium levels closely when bipolar patients start or stop nonsteroidal anti-inflammatory drugs (NSAIDs). Nonprescription ibuprofen can cause serious and even life-threatening serum lithium elevations by affecting lithium’s rate of tubular reabsorption.26 Indomethacin, piroxicam, and selective cyclooxygenase-2 (COX-2) inhibitors also increase plasma lithium concentrations.25
For patients taking lithium with heart drugs, angiotensin-converting enzyme (ACE) inhibitors may increase plasma lithium levels,17 and calcium channel blockers may increase the neurotoxicity risk.17,22 Using the anti-infective metronidazole with lithium may provoke lithium toxicity.
VALPROIC ACID: MONITOR CLEARANCE
Drugs that affect the expression of hepatic enzymes—especially glucuronosyltransferase—may increase clearance of valproic acid and its derivatives. Phenytoin, carbamazepine, or phenobarbital, for example, can double valproic acid clearance.
On the other hand, drugs that inhibit CYP-450 (such as antidepressants) have little effect on valproic acid concentration. Valproate can decrease plasma clearance of amitriptyline, so consider monitoring this tricyclic’s blood levels in patients also taking valproate.17
Because valproic acid can increase serum phenobarbital, monitor barbiturate concentrations when using these two drugs. A similar interaction occurs with primidone, which is metabolized into a barbiturate. Breakthrough seizures may occur with phenytoin, as valproic acid can reduce phenytoin clearance and apparent volume distribution by 25%.22
Using valproic acid with clonazepam may produce absence status in patients with a history of absence-type seizures.17 Valproic acid also displaces diazepam from its plasma albumin binding sites and inhibits its metabolism.
Concomitant use of valproic acid can increase serum concentrations of other antiepileptic drugs. For example, lamotrigine levels may double,24 and felbamate’s peak concentration may increase and require dosage reduction. Valproic acid may also interact with nonpsychiatric medications:
- Subtherapeutic valproic acid levels have been reported when co-administered with the antibiotic meropenem.
- In patients with HIV infection, valproic acid can decrease clearance of the antiretroviral zidovudine by 38%.
- Patients receiving rifampin for tuberculosis may need a dosage adjustment, as oral rifampin’s clearance can increase 40% with concomitant valproic acid.
CARBAMAZEPINE: SELF-INDUCER
Metabolized by CYP 3A4, carbamazepine may induce its own metabolism as well as the CYP 3A4 isoenzyme. Therefore inhibitors and inducers of CYP 3A4 may affect carbamazepine plasma levels.
Carbamazepine can increase plasma levels of other psychotropics including clomipramine, phenytoin, and primidone.17,22 When used with lithium, it may increase the risk of neurotoxic side effects and confusion.23 It can alter thyroid function when used with other anticonvulsants.
For bipolar patients with diabetes, carbamazepine can cause hyperglycemia by inducing the metabolism of oral sulfonylureas such as glipizide and tolbutamide. In women, carbamazepine decreases the reliability of oral contraceptives17 and can cause false-negative pregnancy tests.24
For cancer patients, concurrent carbamazepine may induce metabolism of chemotherapy drugs such as docetaxel, estrogens, paclitaxel, progesterone, and cyclophosphamide, decreasing their efficacy.21 It can increase metabolism of aprepitant and granisetron—used to treat chemotherapy-related nausea—reducing plasma concentrations and possibly efficacy. Carbamazepine’s additive dopamine blockade can increase the risk of extrapyramidal symptoms when used with docetaxel or the antiemetic/antivertigo agents chlorpromazine, metoclopramide, or prochlorperazine.
Carbamazepine increases elimination of some cardiovascular drugs and may decrease the effect of antiarrhythmics such as lidocaine and quinidine; calcium channel blockers such as amlodipine, nifedipine, felodipine, nisoldipine, diltiazem, and verapamil; the beta blocker propranolol; and the vasodilator bosetan.21 Carbamazepine also reduces anticoagulant concentrations, and breakthrough bleeding has been reported.
(See "Out of the Pipeline−extended−release carbamazepine" for a listing of drugs that interact with this agent.)
OTHER ANTICONVULSANTS
Lamotrigine. Some concomitant CNS medications—such as carbamazepine, phenytoin or phenobarbital—reduce lamotrigine serum concentrations by as much as 50%.17 This substantial reduction may give the impression that the patient is not responding to therapeutic lamotrigine doses.
Patients taking lamotrigine with carbamazepine may be at greater risk for dizziness, diplopia, ataxia, and blurred vision because of increased serum concentration of carbamazepine’s epoxide metabolite. Valproic acid doubles lamotrigine serum concentration and increases the risk of rash, whereas lamotrigine decreases valproic acid concentration by 25%.17 Lamotrigine’s manufacturer offers special starting kits for patients taking carbamazepine or valproic acid.
Sertraline increases plasma lamotrigine concentration—but to a lesser extent than does valproic acid17 —and no dosage adjustment is needed.
Topiramate. Concomitant carbamazepine or phenytoin reduces topiramate concentration by 40% to 48%, whereas topiramate increases phenytoin concentration up to 25%. Similarly, valproic acid reduces topiramate’s concentration by 14%, while at the same time valproic acid concentration increases by 11%.17
Topiramate slightly decreases digoxin’s bioavailability and the efficacy of estrogenic oral contraceptives.17,22
Related resources
- Cytochrome P-450 interaction checker. www.drug-interaction.com.
- FDA-reported drug-drug interactions. http://vm.cfsan.fda.gov/~lrd/fdinter.html.
- Psychiatric drug interactions. www.preskorn.com.
- FDA definitions Adverse event: http://www.fda.gov/cder/guidance/iche2a.pdf. Serious adverse event: http://www.fda.gov/medwatch/report/DESK/advevnt.htm.
- Aprepitant • Emend
- Bosentan • Tracleer
- Carbamazepine • Tegretol, others
- Chlorpromazine • Thorazine
- Clomipramine • Anafranil, others
- Clonazepam • Klonopin
- Cyclophosphamide • Cytoxan, Neosar
- Diazepam • Valium
- Diltiazem • Cardizem, others
- Docetaxel • Taxotere
- Felbamate • Felbatol
- Felodipine • Plendil
- Granisetron • Kytril
- Glipizide • Glucotrol
- Haloperidol • Haldol
- Indomethacin • Indocin
- Lamotrigine • Lamictal
- Meropenem • Merrem
- Metoclopramide • Reglan
- Metronidazole • Flagyl
- Nifedipine • Adalat, Procardia
- Nisoldipine • Sular
- Paclitaxel • Taxol, others
- Phenobarbital • Solfoton
- Phenytoin • Dilantin
- Piroxicam • Feldene
- Primidone • Mysoline
- Prochlorperazine • Compazine
- Propranolol • Inderal
- Rifampin • Rifadin
- Sertraline • Zoloft
- Tolbutamide • Orinase
- Topiramate • Topamax
- Valproic acid • Depakote
- Verapamil • Calan, others
- Zidovudine • Retrovir
Dr. Ramadan and Dr. Werder report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Preskorn has received grants or has been a consultant or speaker for Abbott Laboratories, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb Co., Merck & Co., Eisai Inc., Eli Lilly and Co., GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson, Novartis Pharmaceuticals, Organon, Otsuka America Pharmaceutical Inc., Pfizer Inc., Solvay Pharmaceuticals, Sanofi-Aventis, and Wyeth.
Drug-drug interactions (DDIs) can be viewed as physiologic combat wherein a “perpetrator” drug affects a “victim” drug’s pharmacokinetics or pharmacodynamics. Your challenge is to deter that interaction in patients taking two or more medications.
This article—first in a series—discusses polypharmacy risk factors that increase the likelihood of detrimental DDIs, then focuses on DDIs in patients taking mood stabilizers for bipolar disorder. We also offer practical tips to reduce DDI risk. Future articles will discuss DDI risks with antidepressants, antipsychotics, and anxiolytics.
To predict DDIs, you need to know psychotropics’ mechanism of action, metabolism, and effects on cytochrome P-450 (CYP) enzymes. Our discussion is not exhaustive because the data base is massive and new interactions continue to be discovered. Our aim is to equip you to anticipate and prevent DDIs when prescribing.
WHAT ARE ADVERSE DDIs?
An adverse event (AE) is any undesirable experience that occurs when a patient uses a medical product, whether or not the product caused the event. The FDA says an “undesirable experience” may be:
- an unfavorable and unintended symptom or sign
- an abnormal lab or radiographic finding
- a disease that is temporarily associated with the medical product.
An AE becomes “serious” (an SAE) when its duration, intensity, and/or frequency leads to death, a life-threatening condition, initial or prolonged hospitalization, disability, or congenital anomaly. Reporting is voluntary, but we strongly recommend that you report all SAEs to the FDA.
These definitions can help you confirm that a patient has experienced an SAE, but the task becomes more complicated when you try to attribute an SAE to a drug interaction. In the absence of an FDA definition, we assert that DDIs are responsible for SAEs when a perpetrator drug affects the pharmacokinetics or pharmacodynamics of a victim drug and exacerbates a known untoward event of the victim drug (Box 1).1-5 Which drug is the perpetrator and which is the victim is not always clear, and sometimes a medication—such as carbamazepine—can be both at once.
More than 100,000 possible detrimental DDIs have been documented in medical literature and pharmaceutical company data. This number is likely to grow with increased scrutiny, as
DDIs cause morbidity, mortality, and increased health care costs. More than 106,000 Americans die each year from properly prescribed, correctly taken medications. Polypharmacy is associated with extended hospital stays, and using >6 drugs is an independent predictor of death. DDIs contribute to the cause of death in acute overdoses and can be responsible for false-positive suicide diagnoses.
In clinical practice, DDI-associated toxicity may be mistaken for a new disease process, or a disease may be incorrectly perceived as progressing when a medication is rendered ineffective.
Source: References 1-5
RISKS OF POLYPHARMACY
Individuals with psychiatric illnesses are at particular risk for DDIs (Box 2). Patients seen by psychiatrists, for example, are six times more likely than patients seen by primary care physicians to be taking multiple medications.6
Polypharmacy increases the risk of adverse events, nonadherence, medication errors, and drug interactions.7 FDA’s MedWatch Web site lists more than 630 DDI warnings.8 The more medications a patient is taking, the greater the risk for detrimental DDIs and cumulative toxicity,9 which often lead to DDI-induced AEs.10
A study of DDIs in 5,125 mostly older outpatients11 found that:
- 1,594 (31%) had at least one interacting drug combination (average 1.6)
- subjects with one or more DDIs were taking an average 8.1 drugs, compared with 5.2 drugs in those without DDIs—a significant difference
- 155 (3%) had interactions of “major clinical significance.”
- Although drug interactions are responsible for only 3.8% of emergency department visits, patients with DDIs are usually admitted to the hospital.13
- Preventable drug interactions cause approximately one-third of all AEs in hospitalized patients and account for one-half of all AE costs.14
Symptom-based prescribing. Patients with psychiatric illness are often prescribed >1 medication to manage symptoms and signs, rather than a single medication targeting a specific psychiatric disorder.
Multiple prescribers. Patients with anxiety and depressive disorders may see multiple providers, which increases the risk for polypharmacy, drug-drug interactions, and adverse events.
Medical comorbidity. Persons with psychiatric illness are at increased risk for concomitant medical illness, and persons with medical illness are at increased risk for psychiatric illness.
Psychiatric comorbidity. Persons with one psychiatric illness are at increased risk for other psychiatric illnesses.
Source: Adapted from reference 6.
HOW TO MINIMIZE DDI RISK
Use the acronym “LISTEN” (Table 1) to minimize DDI risk in patients taking combination therapies.16 The 6 steps in LISTEN can help you determine which drug or drugs you may discontinue before adding another.
We also recommend that you monitor therapeutic and toxic effects by checking serum drug levels, especially for drugs with a low therapeutic index. Lithium, for example, requires close mentoring of plasma concentration every 2 to 6 months and during dosage adjustments to avoid toxicity.17 Therapeutic drug monitoring has been shown to prevent adverse events from DDIs.16 For added safety, encourage patents to purchase all medications at one pharmacy and to enroll in that pharmacy’s DDI monitoring program.18
Keep in mind that systemic conditions may require a dosage change:
- Increased volume of distribution, as in patients who gain weight or total water volume, requires higher doses to maintain a constant therapeutic effect.
- Reduced clearance, as in patients with decreased renal or hepatic function, will likely require lower doses to prevent toxicity.19
LISTEN: 6 tips to minimize DDI risk
| L | Listeach drug’s name and dosage in the patient’s chart and in a note given to the patient. |
| I | Each drug should have a clear indication and well-defined therapeutic goal; discontinue any drug not achieving its goal |
| S | Make the regimen as simple as possible, with once- or twice-daily dosing. |
| T | When possible, treat multiple symptoms with a single drug, rather than multiple symptoms with multiple drugs |
| E | Educatepatients about polypharmacy, DDIs, and adverse events; assess all medications—including vitamins, minerals, herbs, dietary supplements, nonprescription products—and address potential DDIs |
| N | Avoid prescribing medications with a narrow therapeutic window. |
DDIsWITH MOOD STABILIZERS
Diagnoses of schizophrenia, anxiety disorders, and affective disorders are major risk factors for polypharmacy.20 DDIs are a particular concern in patients with bipolar disorder, given their complex treatment regimens.21
Interactions occur with the most commonly prescribed bipolar medications, including lithium and anticonvulsants (Table 2).17.21-25 Although atypical antipsychotics are also considered mood stabilizers in bipolar disorder, we will discuss their potential DDIs in a future article.
Table 2
Some drug-drug interactions with mood stabilizers
| Mood stabilizer | Drug interactions |
|---|---|
| Carbamazepine | ↑plasma clomipramine, phenytoin, primidone |
| ↑risk of neurotoxic side effects and confusional states with lithium | |
| Alters thyroid function with anticonvulsants | |
| ↓anticoagulant concentrations and↑bleeding risk | |
| ↓oral contraceptive reliability; can cause false-negative pregnancy tests | |
| ↑metabolism and may ↓efficacy of cancer chemotherapy (docetaxel, estrogens, paclitaxel, progesterone, cyclophosphamide) | |
| ↑aprepitant, granisetron metabolism and ↓efficacy | |
| ↑glipizide, tolbutamide metabolism | |
| Lithium | NSAIDs (ibuprofen, indomethacin, piroxicam) and COX-2 inhibitors ↑plasma lithium |
| ACE inhibitors ↑plasma lithium | |
| Calcium channel blockers and carbamazepine ↑lithium neurotoxicity | |
| SSRIs ↑diarrhea, confusion, tremor, dizziness, and agitation | |
| Acetazolamide, urea, xanthine preparations, alkalinizing agents such as sodium bicarbonate ↓plasma lithium | |
| Metronidazole ↑lithium toxicity | |
| Encephalopathic syndrome possible with haloperidol | |
| Lamotrigine | ↑concentration of carbamazepine’s epoxide metabolite |
| Carbamazepine, phenytoin, phenobarbital ↓plasma lamotrigine 40% to 50% | |
| ↑plasma sertraline | |
| ↓plasma valproic acid 25%; valproic acid doubles plasma lamotrigine and ↑rash risk | |
| Topiramate | ↑valproic acid concentrations 11%; valproic acid ↓plasma topiramate 14% |
| ↑plasma phenytoin up to 25%; phenytoin, carbamazepine ↓plasma topiramate by 40% to 48% | |
| ↓digoxin bioavailability | |
| ↓oral contraceptive efficacy | |
| Valproic acid | ↑plasma phenobarbital, primidone |
| ↓phenytoin clearance, volume distribution and ↑breakthrough seizure risk | |
| ↑serum concentration of antiepileptics, such as lamotrigine; absence status possible with clonazepam | |
| ↑= Increases ↓= Decreases | |
| ACE = angiotensin-converting enzyme; COX = cyclooxygenase | |
| NSAIDs = nonsteroidal anti-inflammatory drugs; SSRIs = selective serotonin reuptake inhibitors | |
| Source: References 17, 21-25 | |
LITHIUM: TOXICITY RISK
Lithium is excreted via the kidneys, so be cautious when using lithium in patients taking diuretics.17,22 Drugs that can lower serum lithium concentrations by increasing urinary lithium excretion include acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate.17
Combining lithium with selective serotonin reuptake inhibitors can cause diarrhea, confusion, tremor, dizziness, and agitation.17 An encephalopathic syndrome has occurred in a few patients treated with lithium plus haloperidol.
Monitor lithium levels closely when bipolar patients start or stop nonsteroidal anti-inflammatory drugs (NSAIDs). Nonprescription ibuprofen can cause serious and even life-threatening serum lithium elevations by affecting lithium’s rate of tubular reabsorption.26 Indomethacin, piroxicam, and selective cyclooxygenase-2 (COX-2) inhibitors also increase plasma lithium concentrations.25
For patients taking lithium with heart drugs, angiotensin-converting enzyme (ACE) inhibitors may increase plasma lithium levels,17 and calcium channel blockers may increase the neurotoxicity risk.17,22 Using the anti-infective metronidazole with lithium may provoke lithium toxicity.
VALPROIC ACID: MONITOR CLEARANCE
Drugs that affect the expression of hepatic enzymes—especially glucuronosyltransferase—may increase clearance of valproic acid and its derivatives. Phenytoin, carbamazepine, or phenobarbital, for example, can double valproic acid clearance.
On the other hand, drugs that inhibit CYP-450 (such as antidepressants) have little effect on valproic acid concentration. Valproate can decrease plasma clearance of amitriptyline, so consider monitoring this tricyclic’s blood levels in patients also taking valproate.17
Because valproic acid can increase serum phenobarbital, monitor barbiturate concentrations when using these two drugs. A similar interaction occurs with primidone, which is metabolized into a barbiturate. Breakthrough seizures may occur with phenytoin, as valproic acid can reduce phenytoin clearance and apparent volume distribution by 25%.22
Using valproic acid with clonazepam may produce absence status in patients with a history of absence-type seizures.17 Valproic acid also displaces diazepam from its plasma albumin binding sites and inhibits its metabolism.
Concomitant use of valproic acid can increase serum concentrations of other antiepileptic drugs. For example, lamotrigine levels may double,24 and felbamate’s peak concentration may increase and require dosage reduction. Valproic acid may also interact with nonpsychiatric medications:
- Subtherapeutic valproic acid levels have been reported when co-administered with the antibiotic meropenem.
- In patients with HIV infection, valproic acid can decrease clearance of the antiretroviral zidovudine by 38%.
- Patients receiving rifampin for tuberculosis may need a dosage adjustment, as oral rifampin’s clearance can increase 40% with concomitant valproic acid.
CARBAMAZEPINE: SELF-INDUCER
Metabolized by CYP 3A4, carbamazepine may induce its own metabolism as well as the CYP 3A4 isoenzyme. Therefore inhibitors and inducers of CYP 3A4 may affect carbamazepine plasma levels.
Carbamazepine can increase plasma levels of other psychotropics including clomipramine, phenytoin, and primidone.17,22 When used with lithium, it may increase the risk of neurotoxic side effects and confusion.23 It can alter thyroid function when used with other anticonvulsants.
For bipolar patients with diabetes, carbamazepine can cause hyperglycemia by inducing the metabolism of oral sulfonylureas such as glipizide and tolbutamide. In women, carbamazepine decreases the reliability of oral contraceptives17 and can cause false-negative pregnancy tests.24
For cancer patients, concurrent carbamazepine may induce metabolism of chemotherapy drugs such as docetaxel, estrogens, paclitaxel, progesterone, and cyclophosphamide, decreasing their efficacy.21 It can increase metabolism of aprepitant and granisetron—used to treat chemotherapy-related nausea—reducing plasma concentrations and possibly efficacy. Carbamazepine’s additive dopamine blockade can increase the risk of extrapyramidal symptoms when used with docetaxel or the antiemetic/antivertigo agents chlorpromazine, metoclopramide, or prochlorperazine.
Carbamazepine increases elimination of some cardiovascular drugs and may decrease the effect of antiarrhythmics such as lidocaine and quinidine; calcium channel blockers such as amlodipine, nifedipine, felodipine, nisoldipine, diltiazem, and verapamil; the beta blocker propranolol; and the vasodilator bosetan.21 Carbamazepine also reduces anticoagulant concentrations, and breakthrough bleeding has been reported.
(See "Out of the Pipeline−extended−release carbamazepine" for a listing of drugs that interact with this agent.)
OTHER ANTICONVULSANTS
Lamotrigine. Some concomitant CNS medications—such as carbamazepine, phenytoin or phenobarbital—reduce lamotrigine serum concentrations by as much as 50%.17 This substantial reduction may give the impression that the patient is not responding to therapeutic lamotrigine doses.
Patients taking lamotrigine with carbamazepine may be at greater risk for dizziness, diplopia, ataxia, and blurred vision because of increased serum concentration of carbamazepine’s epoxide metabolite. Valproic acid doubles lamotrigine serum concentration and increases the risk of rash, whereas lamotrigine decreases valproic acid concentration by 25%.17 Lamotrigine’s manufacturer offers special starting kits for patients taking carbamazepine or valproic acid.
Sertraline increases plasma lamotrigine concentration—but to a lesser extent than does valproic acid17 —and no dosage adjustment is needed.
Topiramate. Concomitant carbamazepine or phenytoin reduces topiramate concentration by 40% to 48%, whereas topiramate increases phenytoin concentration up to 25%. Similarly, valproic acid reduces topiramate’s concentration by 14%, while at the same time valproic acid concentration increases by 11%.17
Topiramate slightly decreases digoxin’s bioavailability and the efficacy of estrogenic oral contraceptives.17,22
Related resources
- Cytochrome P-450 interaction checker. www.drug-interaction.com.
- FDA-reported drug-drug interactions. http://vm.cfsan.fda.gov/~lrd/fdinter.html.
- Psychiatric drug interactions. www.preskorn.com.
- FDA definitions Adverse event: http://www.fda.gov/cder/guidance/iche2a.pdf. Serious adverse event: http://www.fda.gov/medwatch/report/DESK/advevnt.htm.
- Aprepitant • Emend
- Bosentan • Tracleer
- Carbamazepine • Tegretol, others
- Chlorpromazine • Thorazine
- Clomipramine • Anafranil, others
- Clonazepam • Klonopin
- Cyclophosphamide • Cytoxan, Neosar
- Diazepam • Valium
- Diltiazem • Cardizem, others
- Docetaxel • Taxotere
- Felbamate • Felbatol
- Felodipine • Plendil
- Granisetron • Kytril
- Glipizide • Glucotrol
- Haloperidol • Haldol
- Indomethacin • Indocin
- Lamotrigine • Lamictal
- Meropenem • Merrem
- Metoclopramide • Reglan
- Metronidazole • Flagyl
- Nifedipine • Adalat, Procardia
- Nisoldipine • Sular
- Paclitaxel • Taxol, others
- Phenobarbital • Solfoton
- Phenytoin • Dilantin
- Piroxicam • Feldene
- Primidone • Mysoline
- Prochlorperazine • Compazine
- Propranolol • Inderal
- Rifampin • Rifadin
- Sertraline • Zoloft
- Tolbutamide • Orinase
- Topiramate • Topamax
- Valproic acid • Depakote
- Verapamil • Calan, others
- Zidovudine • Retrovir
Dr. Ramadan and Dr. Werder report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Preskorn has received grants or has been a consultant or speaker for Abbott Laboratories, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb Co., Merck & Co., Eisai Inc., Eli Lilly and Co., GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson, Novartis Pharmaceuticals, Organon, Otsuka America Pharmaceutical Inc., Pfizer Inc., Solvay Pharmaceuticals, Sanofi-Aventis, and Wyeth.
1. Langdorf MI, Fox JC, Marwah RS, et al. Physician versus computer knowledge of potential drug interactions in the emergency department. Acad Emerg Med 2000;7:1321-9.
2. Lazarou J, Pomeranz BH, Cory PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279(15):1200-5.
3. Incalzi RA, Gemma A, Capparella O, et al. Predicting mortality and length of stay of geriatric patients in an acute care general hospital. J Gerontol 1992;47(2):M35-9.
4. Preskorn SH. Fatal drug-drug interaction as a differential consideration in apparent suicide. J Psychiatr Pract 2002;8(4):233-8.
5. Peterson JF, Bates D. Preventable medication errors: identifying and eliminating serious drug interactions. J Am Pharm Assoc (Wash) 2001;41(2):159-60.
6. Nichol MB, Stimmel GL, Lange SC. Factors predicting the use of multiple psychotropic medications. J Clin Psychiatry 1995;2:60-6.
7. Ananth J, Parameswaran S, Gunatilake S. Antipsychotic polypharmacy. Curr Pharm Des 2004;10(18):2231-8.
8. Medwatch Web site. Food and Drug Administration. Search for Drug-drug interactions. Available at: http://www.fda.gov/med-watch/index.html. Accessed March 31, 2005.
9. Rascati K. Drug utilization review of concomitant use of specific serotonin reuptake inhibitors or clomipramine and antianxiety/sleep medications. Clin Ther 1995;17:786-90.
10. Tanaka E, Hisawa S. Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system. J Clin Pharm Ther 1999;24:7-16.
11. Bergendal L, Friberg A, Schaffrath A. Potential drug-drug interactions in 5,125 mostly elderly outpatients in Gothenburg, Sweden. Pharm World Sci 1995;17(5):152-7.
12. De Las Cuevas C, Sanz EJ. Polypharmacy in psychiatric practice in the Canary Islands. BMC Psychiatry 2004;4(1):18.-
13. Raschetti R, Morgutti M, Menniti Ippolito F, et al. Suspected adverse drug events requiring emergency department visits or hospital admissions. Eur J Clin Pharmacol 1999;54:959-63.
14. Bates DW, Spell N, Cullen DJ, et al. The costs of adverse drug events in hospitalized patients. JAMA 1997;277:307-11.
15. Frye MA, Ketter TA, Leverich GS, et al. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry 2000;1:9-15.
16. Werder SF, Preskorn SH. Managing polypharmacy: walking the fine line between help and harm. Current Psychiatry 2003;2(2):24-36.
17. Physicians’ Desk Reference (59th ed). Montvale, NJ: Thomson PDR; 2005.
18. Sandson NB. Exploring drug interaction in psychiatry. Psychiatric times 2004;May:42-8.
19. Todi SK, Hartmann RA. Pharmacologic principles. In: Civetta JM, Taylor RW, Kirby RR, (eds). Critical care (3rd ed). Philadelphia: Lippincott-Raven Publishers; 1997;485-8.
20. Shapiro LE, Shear NH. Drug interactions: Proteins, pumps, and P-450s. J Am Acad Dermatol 2002;47:467-84.
21. Keck PE, Jr, Dewan N, Nasrallah HA. Bipolar disorder: the clinician’s guide to pharmacotherapy for patients with co-occurring medical conditions. Current Psychiatry 2005;4(Feb)(suppl):1-51.
22. Sadock BJ, Sadock VA. Kaplan and Sadock’s pocket handbook of psychiatric drug treatment (3rd ed). Philadelphia: Lippincott Williams & Wilkins; 2001;144-5,178-83,256-7.
23. Shukla S, Godwin CD, Long LE, Miller MG. Lithium-carbamazepine neurotoxicity and risk factors. Am J Psychiatry 1984;141:1604-6.
24. Licht RW, Vestergaard P, Kessing LV, et al. Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark. Acta Psychiatr Scand Suppl 2003;(419):1-22.
25. Phelan KM, Mosholder AD, Lu S. Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs. J Clin Psychiatry 2003;64:1328-34.
26. Ragheb M, Ban TA, Buchanan D, Frolich JC. Interaction of indomethacin and ibuprofen with lithium in manic patients under steady-state lithium level. J Clin Psychiatry 1980;11:397-8.
1. Langdorf MI, Fox JC, Marwah RS, et al. Physician versus computer knowledge of potential drug interactions in the emergency department. Acad Emerg Med 2000;7:1321-9.
2. Lazarou J, Pomeranz BH, Cory PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279(15):1200-5.
3. Incalzi RA, Gemma A, Capparella O, et al. Predicting mortality and length of stay of geriatric patients in an acute care general hospital. J Gerontol 1992;47(2):M35-9.
4. Preskorn SH. Fatal drug-drug interaction as a differential consideration in apparent suicide. J Psychiatr Pract 2002;8(4):233-8.
5. Peterson JF, Bates D. Preventable medication errors: identifying and eliminating serious drug interactions. J Am Pharm Assoc (Wash) 2001;41(2):159-60.
6. Nichol MB, Stimmel GL, Lange SC. Factors predicting the use of multiple psychotropic medications. J Clin Psychiatry 1995;2:60-6.
7. Ananth J, Parameswaran S, Gunatilake S. Antipsychotic polypharmacy. Curr Pharm Des 2004;10(18):2231-8.
8. Medwatch Web site. Food and Drug Administration. Search for Drug-drug interactions. Available at: http://www.fda.gov/med-watch/index.html. Accessed March 31, 2005.
9. Rascati K. Drug utilization review of concomitant use of specific serotonin reuptake inhibitors or clomipramine and antianxiety/sleep medications. Clin Ther 1995;17:786-90.
10. Tanaka E, Hisawa S. Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system. J Clin Pharm Ther 1999;24:7-16.
11. Bergendal L, Friberg A, Schaffrath A. Potential drug-drug interactions in 5,125 mostly elderly outpatients in Gothenburg, Sweden. Pharm World Sci 1995;17(5):152-7.
12. De Las Cuevas C, Sanz EJ. Polypharmacy in psychiatric practice in the Canary Islands. BMC Psychiatry 2004;4(1):18.-
13. Raschetti R, Morgutti M, Menniti Ippolito F, et al. Suspected adverse drug events requiring emergency department visits or hospital admissions. Eur J Clin Pharmacol 1999;54:959-63.
14. Bates DW, Spell N, Cullen DJ, et al. The costs of adverse drug events in hospitalized patients. JAMA 1997;277:307-11.
15. Frye MA, Ketter TA, Leverich GS, et al. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry 2000;1:9-15.
16. Werder SF, Preskorn SH. Managing polypharmacy: walking the fine line between help and harm. Current Psychiatry 2003;2(2):24-36.
17. Physicians’ Desk Reference (59th ed). Montvale, NJ: Thomson PDR; 2005.
18. Sandson NB. Exploring drug interaction in psychiatry. Psychiatric times 2004;May:42-8.
19. Todi SK, Hartmann RA. Pharmacologic principles. In: Civetta JM, Taylor RW, Kirby RR, (eds). Critical care (3rd ed). Philadelphia: Lippincott-Raven Publishers; 1997;485-8.
20. Shapiro LE, Shear NH. Drug interactions: Proteins, pumps, and P-450s. J Am Acad Dermatol 2002;47:467-84.
21. Keck PE, Jr, Dewan N, Nasrallah HA. Bipolar disorder: the clinician’s guide to pharmacotherapy for patients with co-occurring medical conditions. Current Psychiatry 2005;4(Feb)(suppl):1-51.
22. Sadock BJ, Sadock VA. Kaplan and Sadock’s pocket handbook of psychiatric drug treatment (3rd ed). Philadelphia: Lippincott Williams & Wilkins; 2001;144-5,178-83,256-7.
23. Shukla S, Godwin CD, Long LE, Miller MG. Lithium-carbamazepine neurotoxicity and risk factors. Am J Psychiatry 1984;141:1604-6.
24. Licht RW, Vestergaard P, Kessing LV, et al. Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark. Acta Psychiatr Scand Suppl 2003;(419):1-22.
25. Phelan KM, Mosholder AD, Lu S. Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs. J Clin Psychiatry 2003;64:1328-34.
26. Ragheb M, Ban TA, Buchanan D, Frolich JC. Interaction of indomethacin and ibuprofen with lithium in manic patients under steady-state lithium level. J Clin Psychiatry 1980;11:397-8.
Does AA work? That’s (in part) up to you
Many clinicians refer alcohol-dependent patients to Alcoholics Anonymous, but how effective is AA in reducing drinking? Evidence is elusive—partly because of AA’s tradition of anonymity—but clinician encouragement is among three variables that appear essential to successful AA use.
The pioneer of twelve-step programs (Box 1),1,2 AA is a widely accessible, free adjunct to professional alcohol abuse treatment. This article describes the evidence supporting AA’s efficacy for reducing drinking among persons with alcohol use disorders. We also recommend referral strategies that increase AA participation and discuss special needs of alcohol-dependent patients with comorbid psychiatric disorders.
Alcoholics Anonymous (AA) was founded in 1935 in Akron, OH, by Bill Wilson and Robert Smith, MD, two professionals struggling with alcohol dependence. They joined together to help each other stop drinking.
Their success inspired them to help others, and this mutual-aid society grew under the name Alcoholics Anonymous. AA redefined the then-prevalent view of alcohol dependence as a moral failing, instead conceptualizing it as a disease that can be arrested—but not cured—by alcohol abstinence. The only requirements for AA membership are “a desire to stop drinking,” a respect for maintaining anonymity, and a desire to join a fellowship of mutual support for the goal of abstaining from alcohol.
In 1939, Wilson described AA’s theory and fellowship methods and defined its twelve steps of personal recovery,1 referred to in AA as “The Big Book.” Today, the worldwide fellowship has more than 2 million members, with a male:female ratio of 2:1.2
KEYS TO AA SUCCESS
Besides clinician encouragement, two patient variables—severity of alcohol dependence and self-efficacy—have been associated with successful AA use.
Clinician encouragement. When psychiatrists and other clinicians encourage alcohol-dependent patients to attend AA, the rate of AA use increases and drinking decreases.3-7 When clinicians remain interested in alcohol-dependent patients’ AA use—rather than simply recommending AA—patients are more likely to follow through with a referral and to participate long enough to obtain benefit.
Clinicians play an important role in helping patients benefit from AA referral (Box 2).6 Patients who are personally helped to an AA group will rapidly attend, whereas those only given referral information are unlikely to follow up.7 Moreover, clinicians who encourage patients to attend AA and follow up on that attendance have more patients who attend and participate in AA than do less proactive clinicians.8
Disseminate information about alcohol dependence self-help groups such as AA
Become knowledgeable about local AA options to facilitate referral and cooperation
Invite AA groups to use your institutional or clinic space to hold groups and meetings
Offer appropriate self-help referrals to family members, such as Al-Anon and Al-Ateen family groups
Try to match patient preferences with local AA groups, such as women’s AA, and young people’s AA meetings
Use AA as an adjunct to professional care, rather than stand-alone treatment
Learn about alternatives to 12-step treatments—such as SMART Recovery (a CBT-based treatment), Secular Organization for Sobriety, or Women for Sobriety—for patients who prefer other self-help options
Source: Adapted from Workgroup on Substance Abuse Self-Help Organizations’ expert consensus statement, reference 6.
Self-efficacy. Believing that one can abstain from drinking is associated with being able to reduce one’s drinking. Alcohol-dependent patients with self-efficacy are more likely to use AA, and this trait is believed to be a component of the change process associated with reduced drinking.11,12
HOW EFFECTIVE IS AA?
Randomized, controlled trials (RCTs) may be the “gold standard” for determining any treatment’s efficacy, but constructing an RCT of AA use is complicated. AA does not engage in or support research, which makes AA use difficult to administer as a controlled variable in clinical trials. Also, the variability of AA groups and environments confounds the interpretation of study results and limits their application to populations at large.13
Even so, AA can be effective as an adjunct to professional treatments—such as detoxification—and as aftercare to maintain reduced drinking:
- Kelly’s14 comprehensive review and critical analysis of the main studies through 2003 showed a correlation between professional treatment plus AA attendance and improved outcomes.
- Project MATCH-—a large RCT—also supports AA’s benefits, as reported in smaller, less rigorously controlled studies.4,5
- Kownacki and Shadish15 found poorer 12-month drinking outcomes with AA alone, compared with other treatments or no treatment. Their review assessed attendance as a predictor of alcohol use outcomes, and most subjects were attending AA under court orders. Because AA’s philosophy stresses that members must desire to stop drinking (Table 1), these study results may not apply to the voluntary, motivated individuals who usually use AA.
- Two other meta-analyses9,10 that included nonrandomized studies and RCTs showed that attending AA has modest, favorable effects in reducing drinking and improving psychosocial functioning.
Tonigan et al10 rated 74 studies of alcohol use disorders that measured patients’ affiliation with AA and drinking outcome and/or psychosocial adjustment. Most were cross-sectional inpatient studies; few used collateral interviews or biological measures to confirm self-report data. Most used poor methodology, and their assessments were not psychometrically validated.
Outpatient studies showed positive correlations between AA attendance/involvement and:
- reduced drinking
- improved psychological adjustment and improved family relationships.
All three meta-analyses excluded studies of alcohol-dependent individuals with co-occurring drug use disorders, leaving unaddressed the effect of adjunctive AA in that population.
Table 1
AA’s Twelve Steps of personal recovery
|
| Source: Reprinted with permission, Alcoholics Anonymous World Services (AAWS), Inc. 2005. Permission to reprint does not mean that AAWS has reviewed or approved the contents of this publication, or that AA necessarily agrees with the views expressed herein. |
- 12 sessions of cognitive-behavioral coping skills (CBT)
- 4 sessions of motivational enhancement therapy (MET).
Project MATCH thus found that a twelve-step individual therapy was at least as effective as CBT and MET in reducing post-treatment drinking and maintaining abstinence.
Real-world efficacy. A naturalistic study that resembled Project MATCH enrolled 3,018 male military veterans with substance use disorders across 15 program sites.18 Drug dependence was not excluded, and 51% of the men had co-occurring alcohol and drug dependence.
Participants received inpatient detoxification, followed by 21 to 28 days of intensive twelve-step treatment, CBT, or both. Alcohol and drug abuse declined equally in all three groups, and subjects were referred for outpatient aftercare and self-help groups. After 1 year, involvement in a self-help group predicted better outcome, regardless of the initial treatment.19
Unlike earlier studies,15,20,21 this trial found that individuals with co-occurring psychiatric disorders and those legally mandated to get treatment did as well at 1-year follow-up as those without these variables. It provides additional evidence that twelve-step treatments can reduce substance use across varied populations, including patients with co-occurring alcohol and drug dependence.
AA ATTENDANCE VS. PARTICIPATION
Twelve-step programs appear most effective for individuals who actively participate. This may seem obvious, but most studies of 12-step treatments have monitored meeting attendance rather than engagement. Most studies that separate these variables report that active participation—not passive attendance—correlates with reduced substance use.
Montgomery et al22 followed 66 alcohol-dependent individuals in a 12-step oriented, 28-day residential treatment program and investigated:
- relationships between AA attendance and participation
- drinking outcomes over 31 weeks after treatment.
Similarly, Project MATCH participants involved in AA during the first 6 months after treatment had more-frequent abstinent days in the 7 to 12 months after treatment. AA “involvement” included identifying oneself as an AA member, working the steps, having an AA sponsor, and celebrating sobriety milestones.12
The National Drug Abuse Collaborative Cocaine Treatment Study is the most detailed analysis of self-help use. This multi-site RCT by Weiss and colleagues enrolled 487 individuals for behavioral treatment of cocaine dependence.23
Twelve-step attendance did not predict substance use outcomes, but active participation (such as making coffee for a meeting or reading AA literature) in a given month predicted decreased substance use in the following month. Subjects whose participation increased over the first 3 months showed reduced drug use in the following 3 months. Interestingly, those who participated without attending meetings regularly (such as by reading AA literature or calling a sponsor) benefited as much as those who attended meetings more regularly.
Summary. Actively engaging in 12-step treatment—as measured by identifying with the fellowship and following the steps—appears more important to success than simply attending meetings.
EFFECTIVE AA REFERRALS
To encourage engagement when referring, try to match patients to AA groups attended by persons with whom they feel comfortable (Table 2).24 Adolescents, for example, tend to have more difficulty engaging and remaining in AA than do adults.25 One remedy may be to recommend a Young Person’s AA group composed primarily of adolescents and young adults.
Although AA embraces a spiritual approach to recovery, a person can benefit from participating without having a specific religious affiliation or spiritual beliefs.12,26 The emphasis on spirituality and a “higher power” varies from one AA group to another as well as from region to region. For patients who are uncomfortable with AA’s religiosity, other self-help options for alcohol dependence include SMART Recovery (a CBT-based treatment) and Secular Organization for Sobriety (see Related resources).
Table 2
Matching patients to AA groups:
6 variables to consider
| Variable | Suggestion |
|---|---|
| Socioeconomic status | Match by group location |
| Gender | Women-only groups |
| Age | Young people’s AA |
| Religious content | Beginners’ groups and speaker or topic discussion groups have less-spiritual focus, whereas Step groups and Sunday meetings have more spiritual focus |
| Smoking status | Most groups are smoke-free |
| Drug of choice | Consider AA, Narcotics Anonymous, or a combination of both |
| Source: Reference 29. | |
Some studies20,21—but not all27—suggest that individuals with co-occurring psychiatric disorders have more difficulty participating fully in AA than those without such comorbidity.
Kelly et al20 examined the influence of major depressive disorder (MDD) on AA participation and treatment outcomes in 2,161 men with substance use disorders. During the first year after discharge from inpatient substance-abuse treatment, MDD appeared to have no effect on AA attendance rates or substance abuse outcomes. However, the 110 men with co-occurring MDD showed significantly less social participation in AA—with fewer friends, contacts/calls, and sponsors—and they continued to suffer substantial depression.
This suggests that clinicians could help patients with MDD engage in AA by addressing social anxiety symptoms (how to ask for a sponsor, the importance of establishing and using the AA social network). Carefully monitoring and treating acute depressive symptoms also may enhance AA social participation, especially for patients new to AA.
Impaired social relating is common to many psychiatric disorders—such as psychotic disorders, anxiety disorders, trauma and personality disorders—and social skills training may help other dual-diagnosis patients entering AA. Those with impaired self-control—as with mania or overt psychosis—or inability to maintain interpersonal boundaries are best referred to AA after you stabilize symptoms that would disrupt the group setting.
- Alcoholics Anonymous. General Services Office, PO Box 459, Grand Central Station, New York, NY 10163. Phone (212) 870-3400. www.aa.org
- AA Grapevine: International Journal of Alcoholics Anonymous. http://www.aagrapevine.org.
- National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov
- National Institute on Drug Abuse. http://www.nida.nih.gov/NIDAHome.html
- Cocaine Anonymous. http://www.ca.org
- Narcotics Anonymous. http://www.na.org
- Secular Organizations for Sobriety. http://www.sossobriety.org
- SMART Recovery. http://www.smartrecovery.org
1. Alcoholics Anonymous World Services Inc. Alcoholics Anonymous (4th ed). New York: Alcoholics Anonymous World Services; 2001.
2. Alcoholics Anonymous World Services Inc. AA fact file: what is Alcoholics Anonymous? http://www.aa.org/default/en_about_aa_sub.cfm?subpageid=13&pageid=24.
3. Timko C, Moos RH, Finney JW, Lesar MD. Long-term outcomes of alcohol use disorders: Comparing untreated individuals with those in Alcoholics Anonymous and formal treatment. J Stud Alcohol 2000;61:529-40.
4. Project MATCH Research Group. Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes. Alcohol Clin Exp Res 1998;22(6):1300-11.
5. Project MATCH Research Group. Matching alcoholism treatment to client heterogeneity: Project MATCH post-treatment drinking outcomes. J Stud Alcohol 1997;58:7-29.
6. Humphreys K, Wing S, McCarty D, et al. Self-help organizations for alcohol and drug problems: toward evidence-based practice and policy. J Subst Abuse Treat 2004;26(3):151-8.
7. Sisson RW, Mallams JH. The use of systematic encouragement and community access procedures to increase attendance at Alcoholic Anonymous and Al-Anon meetings. Am J Drug Alcohol Abuse 1981;8(3):371-6.
8. Humphreys K, Huebsch PD, Finney JW, Moos RH. A comparative evaluation of substance abuse treatment: V. Substance abuse treatment can enhance the effectiveness of self-help groups. Alcohol Clin Exp Res 1999;23(3):558-63.
9. Emrick CD, Tonigan JS, Montgomery H, Little L. Alcoholics Anonymous: what is currently known? In: McCrady BS, Miller WR (eds). Research on Alcoholics Anonymous: opportunities and alternatives. New Brunswick, NJ: Rutgers Center of Alcohol Studies; 1993.
10. Tonigan JS, Toscova R, Miller WR. Meta-analysis of the literature on Alcoholics Anonymous: sample and study characteristics moderate findings. J Stud Alcohol 1996;57:65-72.
11. Morgenstern J, Labouvie E, McCrady BS, et al. Affiliation with Alcoholics Anonymous after treatment: a study of its therapeutic effects and mechanisms of action. J Consult Clin Psychol 1997;65(5):768-77.
12. Connors GJ, Tonigan JS, Miller WR, for the MATCH Research Group. A longitudinal model of intake symptomatology, AA participation and outcome: retrospective study of the Project MATCH outpatient and aftercare samples. J Stud Alcohol 2001;62(6):817-25.
13. Montgomery HA, Miller WR, Tonigan JS. Differences among AA groups: implications for research. J Stud Alcohol 1993;54(4):502-4.
14. Kelly JF. Self-help for substance-use disorders: History, effectiveness, knowledge gaps, and research opportunities. Clin Psychol Rev 2003;23:639-63.
15. Kownacki RJ, Shadish WR. Does Alcoholics Anonymous work? The results from a meta-analysis of controlled experiments. Subst Use Misuse 1999;34(13):1897-1916.
16. Project MATCH Research Group. Project MATCH (Matching Alcoholism Treatment to Client Heterogeneity): rationale and methods for a multisite clinical trial matching patients to alcoholism treatment. Alcohol Clin Exp Res 1993;17(6):1130-45.
17. Project MATCH Research Group. Project MATCH secondary a priori hypotheses. Addiction 1997;92(12):1671-98.
18. Ouimette PC, Finney JW, Moos RH. Twelve-step and cognitive-behavioral treatment for substance abuse: A comparison of treatment effectiveness. J Consult Clin Psychol 1997;65(2):230-40.
19. Ouimette PC, Moos RH, Finney JW. Influence of outpatient treatment and 12-step group involvement on one-year substance abuse treatment outcomes. J Stud Alcohol 1998;59:513-22.
20. Kelly JF, McKellar JD, Moos R. Major depression in patients with substance use disorders: relationship to 12-step self-help involvement and substance use outcomes. Addiction 2003;98:499-508.
21. Bogenschutz MP, Akin SJ. Step participation and attitudes toward 12-step meetings in dual diagnosis patients. Alcohol Treat Q 2001;18:31-46.
22. Montgomery HA, Miller WR, Tonigan JS. Does Alcoholics Anonymous involvement predict treatment outcome? J Subst Abuse Treat 1995;12(4):241-6.
23. Weiss RD, Griffin ML, Gallop RJ, et al. The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients. Drug Alcohol Depend 2005;77(2):177-84.
24. Forman RF. One AA meeting doesn’t fit all: 6 keys to prescribing 12-step programs. Current Psychiatry 2002;1(10):16-24.
25. Kelly JF, Myers MG, Brown SA. Do adolescents affiliate with 12-step groups? A multivariate process model of effects. J Stud Alcohol 2002;63:293-304.
26. Winzelberg A, Humphreys K. Should patients’ religiosity influence clinicians’ referral to 12-step self-help groups? Evidence from a study of 3,018 male substance abuse patients. J Consult Clin Psychol 1999;67(5):790-4.
27. Ouimette P, Humphreys K, Moos RH, et al. Self-help group participation among substance use disorder patients with posttraumatic stress disorder. J Subst Abuse Treat 2001;20(1):25-32.
Many clinicians refer alcohol-dependent patients to Alcoholics Anonymous, but how effective is AA in reducing drinking? Evidence is elusive—partly because of AA’s tradition of anonymity—but clinician encouragement is among three variables that appear essential to successful AA use.
The pioneer of twelve-step programs (Box 1),1,2 AA is a widely accessible, free adjunct to professional alcohol abuse treatment. This article describes the evidence supporting AA’s efficacy for reducing drinking among persons with alcohol use disorders. We also recommend referral strategies that increase AA participation and discuss special needs of alcohol-dependent patients with comorbid psychiatric disorders.
Alcoholics Anonymous (AA) was founded in 1935 in Akron, OH, by Bill Wilson and Robert Smith, MD, two professionals struggling with alcohol dependence. They joined together to help each other stop drinking.
Their success inspired them to help others, and this mutual-aid society grew under the name Alcoholics Anonymous. AA redefined the then-prevalent view of alcohol dependence as a moral failing, instead conceptualizing it as a disease that can be arrested—but not cured—by alcohol abstinence. The only requirements for AA membership are “a desire to stop drinking,” a respect for maintaining anonymity, and a desire to join a fellowship of mutual support for the goal of abstaining from alcohol.
In 1939, Wilson described AA’s theory and fellowship methods and defined its twelve steps of personal recovery,1 referred to in AA as “The Big Book.” Today, the worldwide fellowship has more than 2 million members, with a male:female ratio of 2:1.2
KEYS TO AA SUCCESS
Besides clinician encouragement, two patient variables—severity of alcohol dependence and self-efficacy—have been associated with successful AA use.
Clinician encouragement. When psychiatrists and other clinicians encourage alcohol-dependent patients to attend AA, the rate of AA use increases and drinking decreases.3-7 When clinicians remain interested in alcohol-dependent patients’ AA use—rather than simply recommending AA—patients are more likely to follow through with a referral and to participate long enough to obtain benefit.
Clinicians play an important role in helping patients benefit from AA referral (Box 2).6 Patients who are personally helped to an AA group will rapidly attend, whereas those only given referral information are unlikely to follow up.7 Moreover, clinicians who encourage patients to attend AA and follow up on that attendance have more patients who attend and participate in AA than do less proactive clinicians.8
Disseminate information about alcohol dependence self-help groups such as AA
Become knowledgeable about local AA options to facilitate referral and cooperation
Invite AA groups to use your institutional or clinic space to hold groups and meetings
Offer appropriate self-help referrals to family members, such as Al-Anon and Al-Ateen family groups
Try to match patient preferences with local AA groups, such as women’s AA, and young people’s AA meetings
Use AA as an adjunct to professional care, rather than stand-alone treatment
Learn about alternatives to 12-step treatments—such as SMART Recovery (a CBT-based treatment), Secular Organization for Sobriety, or Women for Sobriety—for patients who prefer other self-help options
Source: Adapted from Workgroup on Substance Abuse Self-Help Organizations’ expert consensus statement, reference 6.
Self-efficacy. Believing that one can abstain from drinking is associated with being able to reduce one’s drinking. Alcohol-dependent patients with self-efficacy are more likely to use AA, and this trait is believed to be a component of the change process associated with reduced drinking.11,12
HOW EFFECTIVE IS AA?
Randomized, controlled trials (RCTs) may be the “gold standard” for determining any treatment’s efficacy, but constructing an RCT of AA use is complicated. AA does not engage in or support research, which makes AA use difficult to administer as a controlled variable in clinical trials. Also, the variability of AA groups and environments confounds the interpretation of study results and limits their application to populations at large.13
Even so, AA can be effective as an adjunct to professional treatments—such as detoxification—and as aftercare to maintain reduced drinking:
- Kelly’s14 comprehensive review and critical analysis of the main studies through 2003 showed a correlation between professional treatment plus AA attendance and improved outcomes.
- Project MATCH-—a large RCT—also supports AA’s benefits, as reported in smaller, less rigorously controlled studies.4,5
- Kownacki and Shadish15 found poorer 12-month drinking outcomes with AA alone, compared with other treatments or no treatment. Their review assessed attendance as a predictor of alcohol use outcomes, and most subjects were attending AA under court orders. Because AA’s philosophy stresses that members must desire to stop drinking (Table 1), these study results may not apply to the voluntary, motivated individuals who usually use AA.
- Two other meta-analyses9,10 that included nonrandomized studies and RCTs showed that attending AA has modest, favorable effects in reducing drinking and improving psychosocial functioning.
Tonigan et al10 rated 74 studies of alcohol use disorders that measured patients’ affiliation with AA and drinking outcome and/or psychosocial adjustment. Most were cross-sectional inpatient studies; few used collateral interviews or biological measures to confirm self-report data. Most used poor methodology, and their assessments were not psychometrically validated.
Outpatient studies showed positive correlations between AA attendance/involvement and:
- reduced drinking
- improved psychological adjustment and improved family relationships.
All three meta-analyses excluded studies of alcohol-dependent individuals with co-occurring drug use disorders, leaving unaddressed the effect of adjunctive AA in that population.
Table 1
AA’s Twelve Steps of personal recovery
|
| Source: Reprinted with permission, Alcoholics Anonymous World Services (AAWS), Inc. 2005. Permission to reprint does not mean that AAWS has reviewed or approved the contents of this publication, or that AA necessarily agrees with the views expressed herein. |
- 12 sessions of cognitive-behavioral coping skills (CBT)
- 4 sessions of motivational enhancement therapy (MET).
Project MATCH thus found that a twelve-step individual therapy was at least as effective as CBT and MET in reducing post-treatment drinking and maintaining abstinence.
Real-world efficacy. A naturalistic study that resembled Project MATCH enrolled 3,018 male military veterans with substance use disorders across 15 program sites.18 Drug dependence was not excluded, and 51% of the men had co-occurring alcohol and drug dependence.
Participants received inpatient detoxification, followed by 21 to 28 days of intensive twelve-step treatment, CBT, or both. Alcohol and drug abuse declined equally in all three groups, and subjects were referred for outpatient aftercare and self-help groups. After 1 year, involvement in a self-help group predicted better outcome, regardless of the initial treatment.19
Unlike earlier studies,15,20,21 this trial found that individuals with co-occurring psychiatric disorders and those legally mandated to get treatment did as well at 1-year follow-up as those without these variables. It provides additional evidence that twelve-step treatments can reduce substance use across varied populations, including patients with co-occurring alcohol and drug dependence.
AA ATTENDANCE VS. PARTICIPATION
Twelve-step programs appear most effective for individuals who actively participate. This may seem obvious, but most studies of 12-step treatments have monitored meeting attendance rather than engagement. Most studies that separate these variables report that active participation—not passive attendance—correlates with reduced substance use.
Montgomery et al22 followed 66 alcohol-dependent individuals in a 12-step oriented, 28-day residential treatment program and investigated:
- relationships between AA attendance and participation
- drinking outcomes over 31 weeks after treatment.
Similarly, Project MATCH participants involved in AA during the first 6 months after treatment had more-frequent abstinent days in the 7 to 12 months after treatment. AA “involvement” included identifying oneself as an AA member, working the steps, having an AA sponsor, and celebrating sobriety milestones.12
The National Drug Abuse Collaborative Cocaine Treatment Study is the most detailed analysis of self-help use. This multi-site RCT by Weiss and colleagues enrolled 487 individuals for behavioral treatment of cocaine dependence.23
Twelve-step attendance did not predict substance use outcomes, but active participation (such as making coffee for a meeting or reading AA literature) in a given month predicted decreased substance use in the following month. Subjects whose participation increased over the first 3 months showed reduced drug use in the following 3 months. Interestingly, those who participated without attending meetings regularly (such as by reading AA literature or calling a sponsor) benefited as much as those who attended meetings more regularly.
Summary. Actively engaging in 12-step treatment—as measured by identifying with the fellowship and following the steps—appears more important to success than simply attending meetings.
EFFECTIVE AA REFERRALS
To encourage engagement when referring, try to match patients to AA groups attended by persons with whom they feel comfortable (Table 2).24 Adolescents, for example, tend to have more difficulty engaging and remaining in AA than do adults.25 One remedy may be to recommend a Young Person’s AA group composed primarily of adolescents and young adults.
Although AA embraces a spiritual approach to recovery, a person can benefit from participating without having a specific religious affiliation or spiritual beliefs.12,26 The emphasis on spirituality and a “higher power” varies from one AA group to another as well as from region to region. For patients who are uncomfortable with AA’s religiosity, other self-help options for alcohol dependence include SMART Recovery (a CBT-based treatment) and Secular Organization for Sobriety (see Related resources).
Table 2
Matching patients to AA groups:
6 variables to consider
| Variable | Suggestion |
|---|---|
| Socioeconomic status | Match by group location |
| Gender | Women-only groups |
| Age | Young people’s AA |
| Religious content | Beginners’ groups and speaker or topic discussion groups have less-spiritual focus, whereas Step groups and Sunday meetings have more spiritual focus |
| Smoking status | Most groups are smoke-free |
| Drug of choice | Consider AA, Narcotics Anonymous, or a combination of both |
| Source: Reference 29. | |
Some studies20,21—but not all27—suggest that individuals with co-occurring psychiatric disorders have more difficulty participating fully in AA than those without such comorbidity.
Kelly et al20 examined the influence of major depressive disorder (MDD) on AA participation and treatment outcomes in 2,161 men with substance use disorders. During the first year after discharge from inpatient substance-abuse treatment, MDD appeared to have no effect on AA attendance rates or substance abuse outcomes. However, the 110 men with co-occurring MDD showed significantly less social participation in AA—with fewer friends, contacts/calls, and sponsors—and they continued to suffer substantial depression.
This suggests that clinicians could help patients with MDD engage in AA by addressing social anxiety symptoms (how to ask for a sponsor, the importance of establishing and using the AA social network). Carefully monitoring and treating acute depressive symptoms also may enhance AA social participation, especially for patients new to AA.
Impaired social relating is common to many psychiatric disorders—such as psychotic disorders, anxiety disorders, trauma and personality disorders—and social skills training may help other dual-diagnosis patients entering AA. Those with impaired self-control—as with mania or overt psychosis—or inability to maintain interpersonal boundaries are best referred to AA after you stabilize symptoms that would disrupt the group setting.
- Alcoholics Anonymous. General Services Office, PO Box 459, Grand Central Station, New York, NY 10163. Phone (212) 870-3400. www.aa.org
- AA Grapevine: International Journal of Alcoholics Anonymous. http://www.aagrapevine.org.
- National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov
- National Institute on Drug Abuse. http://www.nida.nih.gov/NIDAHome.html
- Cocaine Anonymous. http://www.ca.org
- Narcotics Anonymous. http://www.na.org
- Secular Organizations for Sobriety. http://www.sossobriety.org
- SMART Recovery. http://www.smartrecovery.org
Many clinicians refer alcohol-dependent patients to Alcoholics Anonymous, but how effective is AA in reducing drinking? Evidence is elusive—partly because of AA’s tradition of anonymity—but clinician encouragement is among three variables that appear essential to successful AA use.
The pioneer of twelve-step programs (Box 1),1,2 AA is a widely accessible, free adjunct to professional alcohol abuse treatment. This article describes the evidence supporting AA’s efficacy for reducing drinking among persons with alcohol use disorders. We also recommend referral strategies that increase AA participation and discuss special needs of alcohol-dependent patients with comorbid psychiatric disorders.
Alcoholics Anonymous (AA) was founded in 1935 in Akron, OH, by Bill Wilson and Robert Smith, MD, two professionals struggling with alcohol dependence. They joined together to help each other stop drinking.
Their success inspired them to help others, and this mutual-aid society grew under the name Alcoholics Anonymous. AA redefined the then-prevalent view of alcohol dependence as a moral failing, instead conceptualizing it as a disease that can be arrested—but not cured—by alcohol abstinence. The only requirements for AA membership are “a desire to stop drinking,” a respect for maintaining anonymity, and a desire to join a fellowship of mutual support for the goal of abstaining from alcohol.
In 1939, Wilson described AA’s theory and fellowship methods and defined its twelve steps of personal recovery,1 referred to in AA as “The Big Book.” Today, the worldwide fellowship has more than 2 million members, with a male:female ratio of 2:1.2
KEYS TO AA SUCCESS
Besides clinician encouragement, two patient variables—severity of alcohol dependence and self-efficacy—have been associated with successful AA use.
Clinician encouragement. When psychiatrists and other clinicians encourage alcohol-dependent patients to attend AA, the rate of AA use increases and drinking decreases.3-7 When clinicians remain interested in alcohol-dependent patients’ AA use—rather than simply recommending AA—patients are more likely to follow through with a referral and to participate long enough to obtain benefit.
Clinicians play an important role in helping patients benefit from AA referral (Box 2).6 Patients who are personally helped to an AA group will rapidly attend, whereas those only given referral information are unlikely to follow up.7 Moreover, clinicians who encourage patients to attend AA and follow up on that attendance have more patients who attend and participate in AA than do less proactive clinicians.8
Disseminate information about alcohol dependence self-help groups such as AA
Become knowledgeable about local AA options to facilitate referral and cooperation
Invite AA groups to use your institutional or clinic space to hold groups and meetings
Offer appropriate self-help referrals to family members, such as Al-Anon and Al-Ateen family groups
Try to match patient preferences with local AA groups, such as women’s AA, and young people’s AA meetings
Use AA as an adjunct to professional care, rather than stand-alone treatment
Learn about alternatives to 12-step treatments—such as SMART Recovery (a CBT-based treatment), Secular Organization for Sobriety, or Women for Sobriety—for patients who prefer other self-help options
Source: Adapted from Workgroup on Substance Abuse Self-Help Organizations’ expert consensus statement, reference 6.
Self-efficacy. Believing that one can abstain from drinking is associated with being able to reduce one’s drinking. Alcohol-dependent patients with self-efficacy are more likely to use AA, and this trait is believed to be a component of the change process associated with reduced drinking.11,12
HOW EFFECTIVE IS AA?
Randomized, controlled trials (RCTs) may be the “gold standard” for determining any treatment’s efficacy, but constructing an RCT of AA use is complicated. AA does not engage in or support research, which makes AA use difficult to administer as a controlled variable in clinical trials. Also, the variability of AA groups and environments confounds the interpretation of study results and limits their application to populations at large.13
Even so, AA can be effective as an adjunct to professional treatments—such as detoxification—and as aftercare to maintain reduced drinking:
- Kelly’s14 comprehensive review and critical analysis of the main studies through 2003 showed a correlation between professional treatment plus AA attendance and improved outcomes.
- Project MATCH-—a large RCT—also supports AA’s benefits, as reported in smaller, less rigorously controlled studies.4,5
- Kownacki and Shadish15 found poorer 12-month drinking outcomes with AA alone, compared with other treatments or no treatment. Their review assessed attendance as a predictor of alcohol use outcomes, and most subjects were attending AA under court orders. Because AA’s philosophy stresses that members must desire to stop drinking (Table 1), these study results may not apply to the voluntary, motivated individuals who usually use AA.
- Two other meta-analyses9,10 that included nonrandomized studies and RCTs showed that attending AA has modest, favorable effects in reducing drinking and improving psychosocial functioning.
Tonigan et al10 rated 74 studies of alcohol use disorders that measured patients’ affiliation with AA and drinking outcome and/or psychosocial adjustment. Most were cross-sectional inpatient studies; few used collateral interviews or biological measures to confirm self-report data. Most used poor methodology, and their assessments were not psychometrically validated.
Outpatient studies showed positive correlations between AA attendance/involvement and:
- reduced drinking
- improved psychological adjustment and improved family relationships.
All three meta-analyses excluded studies of alcohol-dependent individuals with co-occurring drug use disorders, leaving unaddressed the effect of adjunctive AA in that population.
Table 1
AA’s Twelve Steps of personal recovery
|
| Source: Reprinted with permission, Alcoholics Anonymous World Services (AAWS), Inc. 2005. Permission to reprint does not mean that AAWS has reviewed or approved the contents of this publication, or that AA necessarily agrees with the views expressed herein. |
- 12 sessions of cognitive-behavioral coping skills (CBT)
- 4 sessions of motivational enhancement therapy (MET).
Project MATCH thus found that a twelve-step individual therapy was at least as effective as CBT and MET in reducing post-treatment drinking and maintaining abstinence.
Real-world efficacy. A naturalistic study that resembled Project MATCH enrolled 3,018 male military veterans with substance use disorders across 15 program sites.18 Drug dependence was not excluded, and 51% of the men had co-occurring alcohol and drug dependence.
Participants received inpatient detoxification, followed by 21 to 28 days of intensive twelve-step treatment, CBT, or both. Alcohol and drug abuse declined equally in all three groups, and subjects were referred for outpatient aftercare and self-help groups. After 1 year, involvement in a self-help group predicted better outcome, regardless of the initial treatment.19
Unlike earlier studies,15,20,21 this trial found that individuals with co-occurring psychiatric disorders and those legally mandated to get treatment did as well at 1-year follow-up as those without these variables. It provides additional evidence that twelve-step treatments can reduce substance use across varied populations, including patients with co-occurring alcohol and drug dependence.
AA ATTENDANCE VS. PARTICIPATION
Twelve-step programs appear most effective for individuals who actively participate. This may seem obvious, but most studies of 12-step treatments have monitored meeting attendance rather than engagement. Most studies that separate these variables report that active participation—not passive attendance—correlates with reduced substance use.
Montgomery et al22 followed 66 alcohol-dependent individuals in a 12-step oriented, 28-day residential treatment program and investigated:
- relationships between AA attendance and participation
- drinking outcomes over 31 weeks after treatment.
Similarly, Project MATCH participants involved in AA during the first 6 months after treatment had more-frequent abstinent days in the 7 to 12 months after treatment. AA “involvement” included identifying oneself as an AA member, working the steps, having an AA sponsor, and celebrating sobriety milestones.12
The National Drug Abuse Collaborative Cocaine Treatment Study is the most detailed analysis of self-help use. This multi-site RCT by Weiss and colleagues enrolled 487 individuals for behavioral treatment of cocaine dependence.23
Twelve-step attendance did not predict substance use outcomes, but active participation (such as making coffee for a meeting or reading AA literature) in a given month predicted decreased substance use in the following month. Subjects whose participation increased over the first 3 months showed reduced drug use in the following 3 months. Interestingly, those who participated without attending meetings regularly (such as by reading AA literature or calling a sponsor) benefited as much as those who attended meetings more regularly.
Summary. Actively engaging in 12-step treatment—as measured by identifying with the fellowship and following the steps—appears more important to success than simply attending meetings.
EFFECTIVE AA REFERRALS
To encourage engagement when referring, try to match patients to AA groups attended by persons with whom they feel comfortable (Table 2).24 Adolescents, for example, tend to have more difficulty engaging and remaining in AA than do adults.25 One remedy may be to recommend a Young Person’s AA group composed primarily of adolescents and young adults.
Although AA embraces a spiritual approach to recovery, a person can benefit from participating without having a specific religious affiliation or spiritual beliefs.12,26 The emphasis on spirituality and a “higher power” varies from one AA group to another as well as from region to region. For patients who are uncomfortable with AA’s religiosity, other self-help options for alcohol dependence include SMART Recovery (a CBT-based treatment) and Secular Organization for Sobriety (see Related resources).
Table 2
Matching patients to AA groups:
6 variables to consider
| Variable | Suggestion |
|---|---|
| Socioeconomic status | Match by group location |
| Gender | Women-only groups |
| Age | Young people’s AA |
| Religious content | Beginners’ groups and speaker or topic discussion groups have less-spiritual focus, whereas Step groups and Sunday meetings have more spiritual focus |
| Smoking status | Most groups are smoke-free |
| Drug of choice | Consider AA, Narcotics Anonymous, or a combination of both |
| Source: Reference 29. | |
Some studies20,21—but not all27—suggest that individuals with co-occurring psychiatric disorders have more difficulty participating fully in AA than those without such comorbidity.
Kelly et al20 examined the influence of major depressive disorder (MDD) on AA participation and treatment outcomes in 2,161 men with substance use disorders. During the first year after discharge from inpatient substance-abuse treatment, MDD appeared to have no effect on AA attendance rates or substance abuse outcomes. However, the 110 men with co-occurring MDD showed significantly less social participation in AA—with fewer friends, contacts/calls, and sponsors—and they continued to suffer substantial depression.
This suggests that clinicians could help patients with MDD engage in AA by addressing social anxiety symptoms (how to ask for a sponsor, the importance of establishing and using the AA social network). Carefully monitoring and treating acute depressive symptoms also may enhance AA social participation, especially for patients new to AA.
Impaired social relating is common to many psychiatric disorders—such as psychotic disorders, anxiety disorders, trauma and personality disorders—and social skills training may help other dual-diagnosis patients entering AA. Those with impaired self-control—as with mania or overt psychosis—or inability to maintain interpersonal boundaries are best referred to AA after you stabilize symptoms that would disrupt the group setting.
- Alcoholics Anonymous. General Services Office, PO Box 459, Grand Central Station, New York, NY 10163. Phone (212) 870-3400. www.aa.org
- AA Grapevine: International Journal of Alcoholics Anonymous. http://www.aagrapevine.org.
- National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov
- National Institute on Drug Abuse. http://www.nida.nih.gov/NIDAHome.html
- Cocaine Anonymous. http://www.ca.org
- Narcotics Anonymous. http://www.na.org
- Secular Organizations for Sobriety. http://www.sossobriety.org
- SMART Recovery. http://www.smartrecovery.org
1. Alcoholics Anonymous World Services Inc. Alcoholics Anonymous (4th ed). New York: Alcoholics Anonymous World Services; 2001.
2. Alcoholics Anonymous World Services Inc. AA fact file: what is Alcoholics Anonymous? http://www.aa.org/default/en_about_aa_sub.cfm?subpageid=13&pageid=24.
3. Timko C, Moos RH, Finney JW, Lesar MD. Long-term outcomes of alcohol use disorders: Comparing untreated individuals with those in Alcoholics Anonymous and formal treatment. J Stud Alcohol 2000;61:529-40.
4. Project MATCH Research Group. Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes. Alcohol Clin Exp Res 1998;22(6):1300-11.
5. Project MATCH Research Group. Matching alcoholism treatment to client heterogeneity: Project MATCH post-treatment drinking outcomes. J Stud Alcohol 1997;58:7-29.
6. Humphreys K, Wing S, McCarty D, et al. Self-help organizations for alcohol and drug problems: toward evidence-based practice and policy. J Subst Abuse Treat 2004;26(3):151-8.
7. Sisson RW, Mallams JH. The use of systematic encouragement and community access procedures to increase attendance at Alcoholic Anonymous and Al-Anon meetings. Am J Drug Alcohol Abuse 1981;8(3):371-6.
8. Humphreys K, Huebsch PD, Finney JW, Moos RH. A comparative evaluation of substance abuse treatment: V. Substance abuse treatment can enhance the effectiveness of self-help groups. Alcohol Clin Exp Res 1999;23(3):558-63.
9. Emrick CD, Tonigan JS, Montgomery H, Little L. Alcoholics Anonymous: what is currently known? In: McCrady BS, Miller WR (eds). Research on Alcoholics Anonymous: opportunities and alternatives. New Brunswick, NJ: Rutgers Center of Alcohol Studies; 1993.
10. Tonigan JS, Toscova R, Miller WR. Meta-analysis of the literature on Alcoholics Anonymous: sample and study characteristics moderate findings. J Stud Alcohol 1996;57:65-72.
11. Morgenstern J, Labouvie E, McCrady BS, et al. Affiliation with Alcoholics Anonymous after treatment: a study of its therapeutic effects and mechanisms of action. J Consult Clin Psychol 1997;65(5):768-77.
12. Connors GJ, Tonigan JS, Miller WR, for the MATCH Research Group. A longitudinal model of intake symptomatology, AA participation and outcome: retrospective study of the Project MATCH outpatient and aftercare samples. J Stud Alcohol 2001;62(6):817-25.
13. Montgomery HA, Miller WR, Tonigan JS. Differences among AA groups: implications for research. J Stud Alcohol 1993;54(4):502-4.
14. Kelly JF. Self-help for substance-use disorders: History, effectiveness, knowledge gaps, and research opportunities. Clin Psychol Rev 2003;23:639-63.
15. Kownacki RJ, Shadish WR. Does Alcoholics Anonymous work? The results from a meta-analysis of controlled experiments. Subst Use Misuse 1999;34(13):1897-1916.
16. Project MATCH Research Group. Project MATCH (Matching Alcoholism Treatment to Client Heterogeneity): rationale and methods for a multisite clinical trial matching patients to alcoholism treatment. Alcohol Clin Exp Res 1993;17(6):1130-45.
17. Project MATCH Research Group. Project MATCH secondary a priori hypotheses. Addiction 1997;92(12):1671-98.
18. Ouimette PC, Finney JW, Moos RH. Twelve-step and cognitive-behavioral treatment for substance abuse: A comparison of treatment effectiveness. J Consult Clin Psychol 1997;65(2):230-40.
19. Ouimette PC, Moos RH, Finney JW. Influence of outpatient treatment and 12-step group involvement on one-year substance abuse treatment outcomes. J Stud Alcohol 1998;59:513-22.
20. Kelly JF, McKellar JD, Moos R. Major depression in patients with substance use disorders: relationship to 12-step self-help involvement and substance use outcomes. Addiction 2003;98:499-508.
21. Bogenschutz MP, Akin SJ. Step participation and attitudes toward 12-step meetings in dual diagnosis patients. Alcohol Treat Q 2001;18:31-46.
22. Montgomery HA, Miller WR, Tonigan JS. Does Alcoholics Anonymous involvement predict treatment outcome? J Subst Abuse Treat 1995;12(4):241-6.
23. Weiss RD, Griffin ML, Gallop RJ, et al. The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients. Drug Alcohol Depend 2005;77(2):177-84.
24. Forman RF. One AA meeting doesn’t fit all: 6 keys to prescribing 12-step programs. Current Psychiatry 2002;1(10):16-24.
25. Kelly JF, Myers MG, Brown SA. Do adolescents affiliate with 12-step groups? A multivariate process model of effects. J Stud Alcohol 2002;63:293-304.
26. Winzelberg A, Humphreys K. Should patients’ religiosity influence clinicians’ referral to 12-step self-help groups? Evidence from a study of 3,018 male substance abuse patients. J Consult Clin Psychol 1999;67(5):790-4.
27. Ouimette P, Humphreys K, Moos RH, et al. Self-help group participation among substance use disorder patients with posttraumatic stress disorder. J Subst Abuse Treat 2001;20(1):25-32.
1. Alcoholics Anonymous World Services Inc. Alcoholics Anonymous (4th ed). New York: Alcoholics Anonymous World Services; 2001.
2. Alcoholics Anonymous World Services Inc. AA fact file: what is Alcoholics Anonymous? http://www.aa.org/default/en_about_aa_sub.cfm?subpageid=13&pageid=24.
3. Timko C, Moos RH, Finney JW, Lesar MD. Long-term outcomes of alcohol use disorders: Comparing untreated individuals with those in Alcoholics Anonymous and formal treatment. J Stud Alcohol 2000;61:529-40.
4. Project MATCH Research Group. Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes. Alcohol Clin Exp Res 1998;22(6):1300-11.
5. Project MATCH Research Group. Matching alcoholism treatment to client heterogeneity: Project MATCH post-treatment drinking outcomes. J Stud Alcohol 1997;58:7-29.
6. Humphreys K, Wing S, McCarty D, et al. Self-help organizations for alcohol and drug problems: toward evidence-based practice and policy. J Subst Abuse Treat 2004;26(3):151-8.
7. Sisson RW, Mallams JH. The use of systematic encouragement and community access procedures to increase attendance at Alcoholic Anonymous and Al-Anon meetings. Am J Drug Alcohol Abuse 1981;8(3):371-6.
8. Humphreys K, Huebsch PD, Finney JW, Moos RH. A comparative evaluation of substance abuse treatment: V. Substance abuse treatment can enhance the effectiveness of self-help groups. Alcohol Clin Exp Res 1999;23(3):558-63.
9. Emrick CD, Tonigan JS, Montgomery H, Little L. Alcoholics Anonymous: what is currently known? In: McCrady BS, Miller WR (eds). Research on Alcoholics Anonymous: opportunities and alternatives. New Brunswick, NJ: Rutgers Center of Alcohol Studies; 1993.
10. Tonigan JS, Toscova R, Miller WR. Meta-analysis of the literature on Alcoholics Anonymous: sample and study characteristics moderate findings. J Stud Alcohol 1996;57:65-72.
11. Morgenstern J, Labouvie E, McCrady BS, et al. Affiliation with Alcoholics Anonymous after treatment: a study of its therapeutic effects and mechanisms of action. J Consult Clin Psychol 1997;65(5):768-77.
12. Connors GJ, Tonigan JS, Miller WR, for the MATCH Research Group. A longitudinal model of intake symptomatology, AA participation and outcome: retrospective study of the Project MATCH outpatient and aftercare samples. J Stud Alcohol 2001;62(6):817-25.
13. Montgomery HA, Miller WR, Tonigan JS. Differences among AA groups: implications for research. J Stud Alcohol 1993;54(4):502-4.
14. Kelly JF. Self-help for substance-use disorders: History, effectiveness, knowledge gaps, and research opportunities. Clin Psychol Rev 2003;23:639-63.
15. Kownacki RJ, Shadish WR. Does Alcoholics Anonymous work? The results from a meta-analysis of controlled experiments. Subst Use Misuse 1999;34(13):1897-1916.
16. Project MATCH Research Group. Project MATCH (Matching Alcoholism Treatment to Client Heterogeneity): rationale and methods for a multisite clinical trial matching patients to alcoholism treatment. Alcohol Clin Exp Res 1993;17(6):1130-45.
17. Project MATCH Research Group. Project MATCH secondary a priori hypotheses. Addiction 1997;92(12):1671-98.
18. Ouimette PC, Finney JW, Moos RH. Twelve-step and cognitive-behavioral treatment for substance abuse: A comparison of treatment effectiveness. J Consult Clin Psychol 1997;65(2):230-40.
19. Ouimette PC, Moos RH, Finney JW. Influence of outpatient treatment and 12-step group involvement on one-year substance abuse treatment outcomes. J Stud Alcohol 1998;59:513-22.
20. Kelly JF, McKellar JD, Moos R. Major depression in patients with substance use disorders: relationship to 12-step self-help involvement and substance use outcomes. Addiction 2003;98:499-508.
21. Bogenschutz MP, Akin SJ. Step participation and attitudes toward 12-step meetings in dual diagnosis patients. Alcohol Treat Q 2001;18:31-46.
22. Montgomery HA, Miller WR, Tonigan JS. Does Alcoholics Anonymous involvement predict treatment outcome? J Subst Abuse Treat 1995;12(4):241-6.
23. Weiss RD, Griffin ML, Gallop RJ, et al. The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients. Drug Alcohol Depend 2005;77(2):177-84.
24. Forman RF. One AA meeting doesn’t fit all: 6 keys to prescribing 12-step programs. Current Psychiatry 2002;1(10):16-24.
25. Kelly JF, Myers MG, Brown SA. Do adolescents affiliate with 12-step groups? A multivariate process model of effects. J Stud Alcohol 2002;63:293-304.
26. Winzelberg A, Humphreys K. Should patients’ religiosity influence clinicians’ referral to 12-step self-help groups? Evidence from a study of 3,018 male substance abuse patients. J Consult Clin Psychol 1999;67(5):790-4.
27. Ouimette P, Humphreys K, Moos RH, et al. Self-help group participation among substance use disorder patients with posttraumatic stress disorder. J Subst Abuse Treat 2001;20(1):25-32.
ADHD or bipolar disorder? Age-specific manic symptoms are key
Knowing what to look for can help you differentiate between pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD):
- Bipolar disorder is a problem with mood. Children with bipolar mania are elated and/or irritable and experience mood states that appear uncontrollable.
- ADHD is a problem with cognitive functioning, including attention, distractibility, and energy level.
Mood and cognitive symptoms may overlap,1,2 but recognizing manic features is the key to distinguishing between these disorders—even when they co-occur.
We offer tips from our experience and a recent clinical trial to help you sort out the core symptoms that point to bipolar mania.
BIPOLAR CORE SYMPTOMS
Pediatric bipolar disorder is relatively rare, but children with it can experience substantial impairment and developmental delay. Intervening early with effective treatment3 can improve their quality of life, function, and prognosis.
Diagnostic criteria for type I bipolar disorder require at least one manic episode and are the same for all ages. Many clinicians and researchers have advocated adapting DSM-IV criteria for children, but we believe separate adult and pediatric criteria would confuse discussions about the same phenomena. We do agree that symptoms should be evaluated in a developmentally appropriate context, as mania can present differently across the ages (Table 1).
Mania in children and young adolescents tends to present with rapid cycling and a primarily irritable mood.4 Older adolescents and adults may present with more-distinct mood changes, with a primarily euphoric mood. Euphoric mania is less common in adults than previously thought. Forty percent to 60% of adults with bipolar disorder experience a chronic course, rather than more-discrete mood episodes.
A manic episode is an abnormally and persistently elevated (euphoria) or irritable mood that lasts at least 1 week. To satisfy DSM-IV-TR diagnostic criteria for a manic episode:
- patients with euphoria require three additional symptoms
- those who are irritable (and not euphoric) require another four symptoms.5
These symptoms must significantly impair several areas of functioning and not be caused by other mental or physical illness, including substance use or abuse. When depressive symptoms occur in the same week as mania, the mixed mania modifier is used.
Table 1
Diagnostic features of bipolar mania in adolescents vs adults
| Feature | Prepubertal and early adolescent | Older adolescent and adult |
|---|---|---|
| Initial episode | Mixed presentations predominate | Mania is more balanced between mixed and euphoric |
| Episode type | More consistently ill | Persistent/distinct episodes |
| Primary mood | Irritable | Euphoric |
| Duration | Chronic, continuous course | Weeks |
| Inter-episode functioning | Less distinct episodes | May return to baseline or deteriorate over time |
| Reality testing | Delusions (grandiosity) is common; hallucinations | More variable |
Disruptive and aggressive behavior are common and are what usually prompts parents to bring children to psychiatrists. These behaviors are not diagnostic of mania, however, and aggression has many other causes.
The threshold between a variant of normal and pathologic disruptive behavior can be difficult to establish and varies from culture to culture. Some families, for example, would allow a child to tell the parents what to do, whereas other families consider this a serious boundary violation.
Prolonged rages have been used as a proxy for mood swings. Although we agree that rages lasting >15 minutes and out-of-proportion to the circumstances may signal bipolar disorder, they are not diagnostic.
Other symptoms. Psychotic symptoms (hallucinations, delusions, disorganization) can occur in youths with bipolar disorder. Evaluation often reveals impaired social and cognitive development. Keep in mind that a child’s developmental level can affect symptom expression.
ADHD CORE SYMPTOMS
Children with ADHD often present with hyperactive, uncontrollable behaviors and academic failure. To meet DSM-IV-TR diagnostic criteria, they must show symptoms before age 7. Primary symptoms may be inattention, hyperactivity and impulsivity, or both.
ADHD is a disorder of attention and the cognitive skills related to attention, rather than a mood disorder. Children with ADHD show substantially impaired function in at least two settings (such as at home and in school), and—unlike bipolar disorder—their symptoms are persistent rather than episodic.
DIFFERENTIATING BY SYMPTOMS
When differentiating between ADHD and bipolar disorder in children, remain focused on both diagnoses’ core symptoms.
Euphoria, or elation, is a key distinguishing factor in bipolar disorder.6 Although all children are at times giddy or silly in appropriate environments—such as during slumber parties—consider a threshold of appropriateness when making a bipolar diagnosis. Families perceive the giddiness, inappropriate laughter, and elevated mood of children with mania as disturbing and inappropriate, not funny or endearing. They are often annoyed and concerned.
Children with primary ADHD do not show inappropriately elevated mood. In fact, their failures often make these children dysphoric.
Irritability is common in children with psychiatric illnesses. Manic youngsters can be very irritable most of the time. Families describe “walking on eggshells” because of these children’s touchiness. Unpredictable triggers set off explosive, prolonged tantrums that may be associated with aggression, and their mood swings are almost constant.
Children with ADHD can be irritable, but their irritability is less severe and intense than that seen in bipolar disorder. Stimulant medication “wear-off” can cause irritability in ADHD, so consider this possibility if symptoms occur mostly in the evening.
Grandiosity can be confusing to evaluate in children but is often a core symptom in bipolar disorder. All children sometimes say self-inflating things, but those with pathologic grandiosity cross the threshold into the dysfunctional belief that they are better, stronger, smarter, or more talented than others.
For example, a 7-year-old patient insisted he was the world’s best chess player and could beat anyone, including Russian chess masters. When the therapist asked him about chess, he did not know the names of the pieces or how they moved. Yet despite facing these contradictory facts, he continued to insist that he was the best.
Children with grandiosity may act inappropriately on their beliefs, such as by telling adults what to do or engaging in risky, daredevil acts with no concern for their safety or the law.
Children with ADHD are not usually grandiose. Instead, they often become demoralized and develop poor self-esteem from negative feedback about their behavior.
Decreased need for sleep is the hallmark symptom of mania that is absent in other psychiatric disorders. A true decreased need for sleep is only indicated in someone sleeping less than his or her usual cumulative hours each day, without fatigue or recuperative sleep.
Children with bipolar disorder may need 1 or more hours less sleep or deny needing sleep at all. Use age-appropriate amounts of sleep as a standard. A school age child usually averages 9 to 11 hours of sleep per night. If the patient is getting only 6 hours and is not tired, this would be a decreased need for sleep. A 24-hour sleep history can easily assess decreased need for sleep (Box).
Determine daytime fatigue by self-report or observation by parents or teachers. Then ascertain if there are periods of days with less fatigue. Many bipolar youth have a nearly continuous decreased need for sleep.
Children with ADHD often have difficulty settling at night, which delays their falling asleep. The sleep history will likely show that—once asleep—they sleep well for an appropriate amount of time or are fatigued during the day.
Decreased need for sleep is a hallmark symptom of bipolar mania. A 24-hour sleep history may help determine if a child’s irregular sleep patterns signal ADHD or bipolar disorder.
To perform the sleep history, collect time in bed and time asleep over several days, or ask the patient,
- On a typical night, not your best, not your worst:”
- When do you go to bed?
- How long does it take to fall asleep?
- Once asleep, do you wake up?
- How long are you awake?
- When do you arise in the morning?
- What is the total amount of time you are asleep?
- Do you take naps?
- Are you rested or fatigued during the day?
Pressured speech, or the need to talk excessively, is a relatively straightforward symptom. Children experiencing mania often speak so quickly and excessively that others cannot understand or interrupt them. Flight of ideas and racing thoughts are reflected in their speech.
By contrast, rapid speech by children with ADHD is related to hyperactivity. They speak too fast and often become distracted from the topic.
Racing thoughts. Children with bipolar disorder may report that their thoughts come so quickly they cannot get them out fast enough. The idea that their thoughts “need a stop-sign” suggests racing thoughts, a core bipolar symptom. Their speech can be unintelligible, with rapid changes in thought patterns, flight of ideas, and sentence fragments. Children with ADHD are energetic and quick but do not report racing thoughts.
LESS-HELPFUL SYMPTOMS
Distractibility—a core symptom of both inattentive ADHD and manic episodes—does not help differentiate the two diagnoses. The high comorbidity of ADHD with bipolar disorder increases the likelihood that the child will be easily distracted.
Multi-tasking. Increased goal-directed activity is often associated with the high energy of children with mania. They have more energy than most people, are always on the go, and engage in multiple projects or activities that may be markedly creative or unrealistic. This increased energy—combined with other hallmark manic symptoms—can lead to high-risk behaviors.
Hyperactivity in ADHD can appear similar to agitation in bipolar disorder. In both disorders, children may engage in many tasks—not finishing any of them—or appear to move quickly from one task to another.
High-risk behaviors. Parents often report their children with bipolar disorder have tried to jump from moving vehicles, “fly” off of roofs, and jump their bicycles or skateboards over impossible distances. These children behave as if the laws of nature do not apply to them. Children with ADHD behave impulsively but are not always “daredevils.” Their activities appear more impulsive and feature high activity in inappropriate situations, rather than distinctly high-risk activities.
RESPONSE TO THERAPY
Our group7 showed that pediatric manic and ADHD symptoms respond differently to mood-stabilizer treatment (Table 2).
We first used open-label divalproex sodium to treat manic symptoms in 40 children ages 6 to 17 with bipolar I or II disorder and concurrent ADHD. Serum valproic acid levels averaged 82 μg/mL. Manic symptoms improved in 80% of patients, whereas ADHD symptoms improved in <10%. Most children’s symptoms still met severity criteria for ADHD.
In a subsequent double-blind, crossover trial, we compared the effects of mixed amphetamine salts (MAS) or placebo on ADHD symptoms in 30 children whose manic symptoms stabilized on divalproex. MAS showed a significant, independent effect on ADHD symptoms One patient’s manic symptoms recurred during stimulant therapy and subsided with MAS discontinuation.
In this trial, mania symptoms responded to divalproex, whereas ADHD symptoms did not. MAS treatment showed a specific effect on ADHD symptoms of inattention, impulsivity, and hyperactivity. The shared symptoms of mania and ADHD (impulsivity and hyperactivity) decreased with divalproex to some extent.
Table 2
Pediatric mania and ADHD
respond differently to mood-stabilizer therapy
| Children with bipolar I or II disorder and concurrent ADHD | Treatment with divalproex, 8 weeks (N = 40)a | Subjects enter double-blind, crossover treatment with MAS and placebo, 2 weeks each (N = 30) | |
|---|---|---|---|
| Manic symptomsb | 32 of 40 (80%) improved; significant (P <0.0001) | MAS | Placebo |
| No significant change in manic symptoms (P = 0.17) | |||
| ADHD symptomsc | 3 of 40 (7.5%) improved; not significant (P = 0.96) | 26 of 30 (87%) improved | 3 of 30 (10%) improved |
| CGI scores improved 1.9 points more on MAS than on placebo, a significant difference (P <0.0001) | |||
| a Average divalproex blood levels = 82 μg/mL | |||
| b Manic symptom improvement defined as >50% decrease in baseline Young Mania Rating Scale scores | |||
| c ADHD symptom improvement defined as Clinical Global Impression (CGI)–Improvement scores of 1 or 2 | |||
| MAS: Mixed amphetamine salts | |||
| Source: Reference 7 | |||
WHEN MANIA/ADHD CO-OCCUR
ADHD and bipolar disorder symptoms overlap to a great extent, and the disorders can co-occur:
- Up to 20% of children diagnosed with ADHD also meet bipolar criteria.
- Two-thirds of children with bipolar disorder may also meet criteria for ADHD, with reports ranging from 29% to 98%.1,2
When trying to differentiate ADHD and bipolar disorder in children, consider the core symptoms of each diagnosis (Table 3).
Table 3
Core symptoms: Pediatric bipolar disorder vs ADHD
| Symptom | Bipolar disorder | ADHD |
|---|---|---|
| Euphoria/giddiness | Excessive | Appropriate to situations |
| Irritability | Severe and intense, often accompanied by tantrums | Occasional, may be caused by medication “wear-off” |
| Self-esteem | Grandiose | Demoralized |
| Sleep patterns | Decreased need for sleep | Difficulty settling at night |
| Speech patterns | Pressured, fragmented, with flight of ideas | Energetic and quick |
| Thought processes | Racing thoughts | Patients do not report racing thoughts |
| Psychosis can occur at times | ||
| Attention | Distractible | Distractible |
| Activity level | High energy, on-the-go, multiple projects, creative | Hyperactive, multiple projects |
| High-risk behaviors | Impulsive | |
| Disruptive behaviors | Can become aggressive | Intrusive and active |
Related resources
- Geller B, DelBello MP (eds). Bipolar disorder in childhood and early adolescence. New York: Guilford Press, 2003.
- Papolos DF, Papolos J. Bipolar child: The definitive and reassuring guide to childhood’s most misunderstood disorder. New York: Broadway Books, 2002.
- Fristad MA, Goldberg Arnold JS. Raising a moody child: How to cope with depression and bipolar disorder. New York: Guilford Press, 2003.
- Child and Adolescent Bipolar Foundation. Available at www.cabf.org. Accessed March 4, 2005.
Drug brand names
- Divalproex sodium • Depakote
- Mixed amphetamine salts • Adderall
Disclosures
Dr. Scheffer receives research support from and is a speaker for Abbott Laboratories.
Dr. Apps reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Wozniak J, Biederman J, Kiely K, et al. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry 1995;34(7):867-76.
2. Biederman J, Faraone S, Mick E, et al. Attention-deficit hyperactivity disorder and juvenile mania: an overlooked comorbidity? J Am Acad Child Adolesc Psychiatry 1996;35(8):997-1008.
3. Patel NC, Sallee FR. What’s the best treatment for ADHD/bipolar mania? Current Psychiatry 2005;3(3):27-37.
4. Geller B, Tillman R, Craney JL, Bolhofner K. Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype. Arch Gen Psychiatry 2004;61:459-67.
5. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed., rev). Washington, DC: American Psychiatric Association, 2000.
6. Geller B, Williams M, Zimerman B, et al. Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling. J Affect Disord 1998;51(2):81-91.
7. Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry 2005;162(1):58-64.
Knowing what to look for can help you differentiate between pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD):
- Bipolar disorder is a problem with mood. Children with bipolar mania are elated and/or irritable and experience mood states that appear uncontrollable.
- ADHD is a problem with cognitive functioning, including attention, distractibility, and energy level.
Mood and cognitive symptoms may overlap,1,2 but recognizing manic features is the key to distinguishing between these disorders—even when they co-occur.
We offer tips from our experience and a recent clinical trial to help you sort out the core symptoms that point to bipolar mania.
BIPOLAR CORE SYMPTOMS
Pediatric bipolar disorder is relatively rare, but children with it can experience substantial impairment and developmental delay. Intervening early with effective treatment3 can improve their quality of life, function, and prognosis.
Diagnostic criteria for type I bipolar disorder require at least one manic episode and are the same for all ages. Many clinicians and researchers have advocated adapting DSM-IV criteria for children, but we believe separate adult and pediatric criteria would confuse discussions about the same phenomena. We do agree that symptoms should be evaluated in a developmentally appropriate context, as mania can present differently across the ages (Table 1).
Mania in children and young adolescents tends to present with rapid cycling and a primarily irritable mood.4 Older adolescents and adults may present with more-distinct mood changes, with a primarily euphoric mood. Euphoric mania is less common in adults than previously thought. Forty percent to 60% of adults with bipolar disorder experience a chronic course, rather than more-discrete mood episodes.
A manic episode is an abnormally and persistently elevated (euphoria) or irritable mood that lasts at least 1 week. To satisfy DSM-IV-TR diagnostic criteria for a manic episode:
- patients with euphoria require three additional symptoms
- those who are irritable (and not euphoric) require another four symptoms.5
These symptoms must significantly impair several areas of functioning and not be caused by other mental or physical illness, including substance use or abuse. When depressive symptoms occur in the same week as mania, the mixed mania modifier is used.
Table 1
Diagnostic features of bipolar mania in adolescents vs adults
| Feature | Prepubertal and early adolescent | Older adolescent and adult |
|---|---|---|
| Initial episode | Mixed presentations predominate | Mania is more balanced between mixed and euphoric |
| Episode type | More consistently ill | Persistent/distinct episodes |
| Primary mood | Irritable | Euphoric |
| Duration | Chronic, continuous course | Weeks |
| Inter-episode functioning | Less distinct episodes | May return to baseline or deteriorate over time |
| Reality testing | Delusions (grandiosity) is common; hallucinations | More variable |
Disruptive and aggressive behavior are common and are what usually prompts parents to bring children to psychiatrists. These behaviors are not diagnostic of mania, however, and aggression has many other causes.
The threshold between a variant of normal and pathologic disruptive behavior can be difficult to establish and varies from culture to culture. Some families, for example, would allow a child to tell the parents what to do, whereas other families consider this a serious boundary violation.
Prolonged rages have been used as a proxy for mood swings. Although we agree that rages lasting >15 minutes and out-of-proportion to the circumstances may signal bipolar disorder, they are not diagnostic.
Other symptoms. Psychotic symptoms (hallucinations, delusions, disorganization) can occur in youths with bipolar disorder. Evaluation often reveals impaired social and cognitive development. Keep in mind that a child’s developmental level can affect symptom expression.
ADHD CORE SYMPTOMS
Children with ADHD often present with hyperactive, uncontrollable behaviors and academic failure. To meet DSM-IV-TR diagnostic criteria, they must show symptoms before age 7. Primary symptoms may be inattention, hyperactivity and impulsivity, or both.
ADHD is a disorder of attention and the cognitive skills related to attention, rather than a mood disorder. Children with ADHD show substantially impaired function in at least two settings (such as at home and in school), and—unlike bipolar disorder—their symptoms are persistent rather than episodic.
DIFFERENTIATING BY SYMPTOMS
When differentiating between ADHD and bipolar disorder in children, remain focused on both diagnoses’ core symptoms.
Euphoria, or elation, is a key distinguishing factor in bipolar disorder.6 Although all children are at times giddy or silly in appropriate environments—such as during slumber parties—consider a threshold of appropriateness when making a bipolar diagnosis. Families perceive the giddiness, inappropriate laughter, and elevated mood of children with mania as disturbing and inappropriate, not funny or endearing. They are often annoyed and concerned.
Children with primary ADHD do not show inappropriately elevated mood. In fact, their failures often make these children dysphoric.
Irritability is common in children with psychiatric illnesses. Manic youngsters can be very irritable most of the time. Families describe “walking on eggshells” because of these children’s touchiness. Unpredictable triggers set off explosive, prolonged tantrums that may be associated with aggression, and their mood swings are almost constant.
Children with ADHD can be irritable, but their irritability is less severe and intense than that seen in bipolar disorder. Stimulant medication “wear-off” can cause irritability in ADHD, so consider this possibility if symptoms occur mostly in the evening.
Grandiosity can be confusing to evaluate in children but is often a core symptom in bipolar disorder. All children sometimes say self-inflating things, but those with pathologic grandiosity cross the threshold into the dysfunctional belief that they are better, stronger, smarter, or more talented than others.
For example, a 7-year-old patient insisted he was the world’s best chess player and could beat anyone, including Russian chess masters. When the therapist asked him about chess, he did not know the names of the pieces or how they moved. Yet despite facing these contradictory facts, he continued to insist that he was the best.
Children with grandiosity may act inappropriately on their beliefs, such as by telling adults what to do or engaging in risky, daredevil acts with no concern for their safety or the law.
Children with ADHD are not usually grandiose. Instead, they often become demoralized and develop poor self-esteem from negative feedback about their behavior.
Decreased need for sleep is the hallmark symptom of mania that is absent in other psychiatric disorders. A true decreased need for sleep is only indicated in someone sleeping less than his or her usual cumulative hours each day, without fatigue or recuperative sleep.
Children with bipolar disorder may need 1 or more hours less sleep or deny needing sleep at all. Use age-appropriate amounts of sleep as a standard. A school age child usually averages 9 to 11 hours of sleep per night. If the patient is getting only 6 hours and is not tired, this would be a decreased need for sleep. A 24-hour sleep history can easily assess decreased need for sleep (Box).
Determine daytime fatigue by self-report or observation by parents or teachers. Then ascertain if there are periods of days with less fatigue. Many bipolar youth have a nearly continuous decreased need for sleep.
Children with ADHD often have difficulty settling at night, which delays their falling asleep. The sleep history will likely show that—once asleep—they sleep well for an appropriate amount of time or are fatigued during the day.
Decreased need for sleep is a hallmark symptom of bipolar mania. A 24-hour sleep history may help determine if a child’s irregular sleep patterns signal ADHD or bipolar disorder.
To perform the sleep history, collect time in bed and time asleep over several days, or ask the patient,
- On a typical night, not your best, not your worst:”
- When do you go to bed?
- How long does it take to fall asleep?
- Once asleep, do you wake up?
- How long are you awake?
- When do you arise in the morning?
- What is the total amount of time you are asleep?
- Do you take naps?
- Are you rested or fatigued during the day?
Pressured speech, or the need to talk excessively, is a relatively straightforward symptom. Children experiencing mania often speak so quickly and excessively that others cannot understand or interrupt them. Flight of ideas and racing thoughts are reflected in their speech.
By contrast, rapid speech by children with ADHD is related to hyperactivity. They speak too fast and often become distracted from the topic.
Racing thoughts. Children with bipolar disorder may report that their thoughts come so quickly they cannot get them out fast enough. The idea that their thoughts “need a stop-sign” suggests racing thoughts, a core bipolar symptom. Their speech can be unintelligible, with rapid changes in thought patterns, flight of ideas, and sentence fragments. Children with ADHD are energetic and quick but do not report racing thoughts.
LESS-HELPFUL SYMPTOMS
Distractibility—a core symptom of both inattentive ADHD and manic episodes—does not help differentiate the two diagnoses. The high comorbidity of ADHD with bipolar disorder increases the likelihood that the child will be easily distracted.
Multi-tasking. Increased goal-directed activity is often associated with the high energy of children with mania. They have more energy than most people, are always on the go, and engage in multiple projects or activities that may be markedly creative or unrealistic. This increased energy—combined with other hallmark manic symptoms—can lead to high-risk behaviors.
Hyperactivity in ADHD can appear similar to agitation in bipolar disorder. In both disorders, children may engage in many tasks—not finishing any of them—or appear to move quickly from one task to another.
High-risk behaviors. Parents often report their children with bipolar disorder have tried to jump from moving vehicles, “fly” off of roofs, and jump their bicycles or skateboards over impossible distances. These children behave as if the laws of nature do not apply to them. Children with ADHD behave impulsively but are not always “daredevils.” Their activities appear more impulsive and feature high activity in inappropriate situations, rather than distinctly high-risk activities.
RESPONSE TO THERAPY
Our group7 showed that pediatric manic and ADHD symptoms respond differently to mood-stabilizer treatment (Table 2).
We first used open-label divalproex sodium to treat manic symptoms in 40 children ages 6 to 17 with bipolar I or II disorder and concurrent ADHD. Serum valproic acid levels averaged 82 μg/mL. Manic symptoms improved in 80% of patients, whereas ADHD symptoms improved in <10%. Most children’s symptoms still met severity criteria for ADHD.
In a subsequent double-blind, crossover trial, we compared the effects of mixed amphetamine salts (MAS) or placebo on ADHD symptoms in 30 children whose manic symptoms stabilized on divalproex. MAS showed a significant, independent effect on ADHD symptoms One patient’s manic symptoms recurred during stimulant therapy and subsided with MAS discontinuation.
In this trial, mania symptoms responded to divalproex, whereas ADHD symptoms did not. MAS treatment showed a specific effect on ADHD symptoms of inattention, impulsivity, and hyperactivity. The shared symptoms of mania and ADHD (impulsivity and hyperactivity) decreased with divalproex to some extent.
Table 2
Pediatric mania and ADHD
respond differently to mood-stabilizer therapy
| Children with bipolar I or II disorder and concurrent ADHD | Treatment with divalproex, 8 weeks (N = 40)a | Subjects enter double-blind, crossover treatment with MAS and placebo, 2 weeks each (N = 30) | |
|---|---|---|---|
| Manic symptomsb | 32 of 40 (80%) improved; significant (P <0.0001) | MAS | Placebo |
| No significant change in manic symptoms (P = 0.17) | |||
| ADHD symptomsc | 3 of 40 (7.5%) improved; not significant (P = 0.96) | 26 of 30 (87%) improved | 3 of 30 (10%) improved |
| CGI scores improved 1.9 points more on MAS than on placebo, a significant difference (P <0.0001) | |||
| a Average divalproex blood levels = 82 μg/mL | |||
| b Manic symptom improvement defined as >50% decrease in baseline Young Mania Rating Scale scores | |||
| c ADHD symptom improvement defined as Clinical Global Impression (CGI)–Improvement scores of 1 or 2 | |||
| MAS: Mixed amphetamine salts | |||
| Source: Reference 7 | |||
WHEN MANIA/ADHD CO-OCCUR
ADHD and bipolar disorder symptoms overlap to a great extent, and the disorders can co-occur:
- Up to 20% of children diagnosed with ADHD also meet bipolar criteria.
- Two-thirds of children with bipolar disorder may also meet criteria for ADHD, with reports ranging from 29% to 98%.1,2
When trying to differentiate ADHD and bipolar disorder in children, consider the core symptoms of each diagnosis (Table 3).
Table 3
Core symptoms: Pediatric bipolar disorder vs ADHD
| Symptom | Bipolar disorder | ADHD |
|---|---|---|
| Euphoria/giddiness | Excessive | Appropriate to situations |
| Irritability | Severe and intense, often accompanied by tantrums | Occasional, may be caused by medication “wear-off” |
| Self-esteem | Grandiose | Demoralized |
| Sleep patterns | Decreased need for sleep | Difficulty settling at night |
| Speech patterns | Pressured, fragmented, with flight of ideas | Energetic and quick |
| Thought processes | Racing thoughts | Patients do not report racing thoughts |
| Psychosis can occur at times | ||
| Attention | Distractible | Distractible |
| Activity level | High energy, on-the-go, multiple projects, creative | Hyperactive, multiple projects |
| High-risk behaviors | Impulsive | |
| Disruptive behaviors | Can become aggressive | Intrusive and active |
Related resources
- Geller B, DelBello MP (eds). Bipolar disorder in childhood and early adolescence. New York: Guilford Press, 2003.
- Papolos DF, Papolos J. Bipolar child: The definitive and reassuring guide to childhood’s most misunderstood disorder. New York: Broadway Books, 2002.
- Fristad MA, Goldberg Arnold JS. Raising a moody child: How to cope with depression and bipolar disorder. New York: Guilford Press, 2003.
- Child and Adolescent Bipolar Foundation. Available at www.cabf.org. Accessed March 4, 2005.
Drug brand names
- Divalproex sodium • Depakote
- Mixed amphetamine salts • Adderall
Disclosures
Dr. Scheffer receives research support from and is a speaker for Abbott Laboratories.
Dr. Apps reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Knowing what to look for can help you differentiate between pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD):
- Bipolar disorder is a problem with mood. Children with bipolar mania are elated and/or irritable and experience mood states that appear uncontrollable.
- ADHD is a problem with cognitive functioning, including attention, distractibility, and energy level.
Mood and cognitive symptoms may overlap,1,2 but recognizing manic features is the key to distinguishing between these disorders—even when they co-occur.
We offer tips from our experience and a recent clinical trial to help you sort out the core symptoms that point to bipolar mania.
BIPOLAR CORE SYMPTOMS
Pediatric bipolar disorder is relatively rare, but children with it can experience substantial impairment and developmental delay. Intervening early with effective treatment3 can improve their quality of life, function, and prognosis.
Diagnostic criteria for type I bipolar disorder require at least one manic episode and are the same for all ages. Many clinicians and researchers have advocated adapting DSM-IV criteria for children, but we believe separate adult and pediatric criteria would confuse discussions about the same phenomena. We do agree that symptoms should be evaluated in a developmentally appropriate context, as mania can present differently across the ages (Table 1).
Mania in children and young adolescents tends to present with rapid cycling and a primarily irritable mood.4 Older adolescents and adults may present with more-distinct mood changes, with a primarily euphoric mood. Euphoric mania is less common in adults than previously thought. Forty percent to 60% of adults with bipolar disorder experience a chronic course, rather than more-discrete mood episodes.
A manic episode is an abnormally and persistently elevated (euphoria) or irritable mood that lasts at least 1 week. To satisfy DSM-IV-TR diagnostic criteria for a manic episode:
- patients with euphoria require three additional symptoms
- those who are irritable (and not euphoric) require another four symptoms.5
These symptoms must significantly impair several areas of functioning and not be caused by other mental or physical illness, including substance use or abuse. When depressive symptoms occur in the same week as mania, the mixed mania modifier is used.
Table 1
Diagnostic features of bipolar mania in adolescents vs adults
| Feature | Prepubertal and early adolescent | Older adolescent and adult |
|---|---|---|
| Initial episode | Mixed presentations predominate | Mania is more balanced between mixed and euphoric |
| Episode type | More consistently ill | Persistent/distinct episodes |
| Primary mood | Irritable | Euphoric |
| Duration | Chronic, continuous course | Weeks |
| Inter-episode functioning | Less distinct episodes | May return to baseline or deteriorate over time |
| Reality testing | Delusions (grandiosity) is common; hallucinations | More variable |
Disruptive and aggressive behavior are common and are what usually prompts parents to bring children to psychiatrists. These behaviors are not diagnostic of mania, however, and aggression has many other causes.
The threshold between a variant of normal and pathologic disruptive behavior can be difficult to establish and varies from culture to culture. Some families, for example, would allow a child to tell the parents what to do, whereas other families consider this a serious boundary violation.
Prolonged rages have been used as a proxy for mood swings. Although we agree that rages lasting >15 minutes and out-of-proportion to the circumstances may signal bipolar disorder, they are not diagnostic.
Other symptoms. Psychotic symptoms (hallucinations, delusions, disorganization) can occur in youths with bipolar disorder. Evaluation often reveals impaired social and cognitive development. Keep in mind that a child’s developmental level can affect symptom expression.
ADHD CORE SYMPTOMS
Children with ADHD often present with hyperactive, uncontrollable behaviors and academic failure. To meet DSM-IV-TR diagnostic criteria, they must show symptoms before age 7. Primary symptoms may be inattention, hyperactivity and impulsivity, or both.
ADHD is a disorder of attention and the cognitive skills related to attention, rather than a mood disorder. Children with ADHD show substantially impaired function in at least two settings (such as at home and in school), and—unlike bipolar disorder—their symptoms are persistent rather than episodic.
DIFFERENTIATING BY SYMPTOMS
When differentiating between ADHD and bipolar disorder in children, remain focused on both diagnoses’ core symptoms.
Euphoria, or elation, is a key distinguishing factor in bipolar disorder.6 Although all children are at times giddy or silly in appropriate environments—such as during slumber parties—consider a threshold of appropriateness when making a bipolar diagnosis. Families perceive the giddiness, inappropriate laughter, and elevated mood of children with mania as disturbing and inappropriate, not funny or endearing. They are often annoyed and concerned.
Children with primary ADHD do not show inappropriately elevated mood. In fact, their failures often make these children dysphoric.
Irritability is common in children with psychiatric illnesses. Manic youngsters can be very irritable most of the time. Families describe “walking on eggshells” because of these children’s touchiness. Unpredictable triggers set off explosive, prolonged tantrums that may be associated with aggression, and their mood swings are almost constant.
Children with ADHD can be irritable, but their irritability is less severe and intense than that seen in bipolar disorder. Stimulant medication “wear-off” can cause irritability in ADHD, so consider this possibility if symptoms occur mostly in the evening.
Grandiosity can be confusing to evaluate in children but is often a core symptom in bipolar disorder. All children sometimes say self-inflating things, but those with pathologic grandiosity cross the threshold into the dysfunctional belief that they are better, stronger, smarter, or more talented than others.
For example, a 7-year-old patient insisted he was the world’s best chess player and could beat anyone, including Russian chess masters. When the therapist asked him about chess, he did not know the names of the pieces or how they moved. Yet despite facing these contradictory facts, he continued to insist that he was the best.
Children with grandiosity may act inappropriately on their beliefs, such as by telling adults what to do or engaging in risky, daredevil acts with no concern for their safety or the law.
Children with ADHD are not usually grandiose. Instead, they often become demoralized and develop poor self-esteem from negative feedback about their behavior.
Decreased need for sleep is the hallmark symptom of mania that is absent in other psychiatric disorders. A true decreased need for sleep is only indicated in someone sleeping less than his or her usual cumulative hours each day, without fatigue or recuperative sleep.
Children with bipolar disorder may need 1 or more hours less sleep or deny needing sleep at all. Use age-appropriate amounts of sleep as a standard. A school age child usually averages 9 to 11 hours of sleep per night. If the patient is getting only 6 hours and is not tired, this would be a decreased need for sleep. A 24-hour sleep history can easily assess decreased need for sleep (Box).
Determine daytime fatigue by self-report or observation by parents or teachers. Then ascertain if there are periods of days with less fatigue. Many bipolar youth have a nearly continuous decreased need for sleep.
Children with ADHD often have difficulty settling at night, which delays their falling asleep. The sleep history will likely show that—once asleep—they sleep well for an appropriate amount of time or are fatigued during the day.
Decreased need for sleep is a hallmark symptom of bipolar mania. A 24-hour sleep history may help determine if a child’s irregular sleep patterns signal ADHD or bipolar disorder.
To perform the sleep history, collect time in bed and time asleep over several days, or ask the patient,
- On a typical night, not your best, not your worst:”
- When do you go to bed?
- How long does it take to fall asleep?
- Once asleep, do you wake up?
- How long are you awake?
- When do you arise in the morning?
- What is the total amount of time you are asleep?
- Do you take naps?
- Are you rested or fatigued during the day?
Pressured speech, or the need to talk excessively, is a relatively straightforward symptom. Children experiencing mania often speak so quickly and excessively that others cannot understand or interrupt them. Flight of ideas and racing thoughts are reflected in their speech.
By contrast, rapid speech by children with ADHD is related to hyperactivity. They speak too fast and often become distracted from the topic.
Racing thoughts. Children with bipolar disorder may report that their thoughts come so quickly they cannot get them out fast enough. The idea that their thoughts “need a stop-sign” suggests racing thoughts, a core bipolar symptom. Their speech can be unintelligible, with rapid changes in thought patterns, flight of ideas, and sentence fragments. Children with ADHD are energetic and quick but do not report racing thoughts.
LESS-HELPFUL SYMPTOMS
Distractibility—a core symptom of both inattentive ADHD and manic episodes—does not help differentiate the two diagnoses. The high comorbidity of ADHD with bipolar disorder increases the likelihood that the child will be easily distracted.
Multi-tasking. Increased goal-directed activity is often associated with the high energy of children with mania. They have more energy than most people, are always on the go, and engage in multiple projects or activities that may be markedly creative or unrealistic. This increased energy—combined with other hallmark manic symptoms—can lead to high-risk behaviors.
Hyperactivity in ADHD can appear similar to agitation in bipolar disorder. In both disorders, children may engage in many tasks—not finishing any of them—or appear to move quickly from one task to another.
High-risk behaviors. Parents often report their children with bipolar disorder have tried to jump from moving vehicles, “fly” off of roofs, and jump their bicycles or skateboards over impossible distances. These children behave as if the laws of nature do not apply to them. Children with ADHD behave impulsively but are not always “daredevils.” Their activities appear more impulsive and feature high activity in inappropriate situations, rather than distinctly high-risk activities.
RESPONSE TO THERAPY
Our group7 showed that pediatric manic and ADHD symptoms respond differently to mood-stabilizer treatment (Table 2).
We first used open-label divalproex sodium to treat manic symptoms in 40 children ages 6 to 17 with bipolar I or II disorder and concurrent ADHD. Serum valproic acid levels averaged 82 μg/mL. Manic symptoms improved in 80% of patients, whereas ADHD symptoms improved in <10%. Most children’s symptoms still met severity criteria for ADHD.
In a subsequent double-blind, crossover trial, we compared the effects of mixed amphetamine salts (MAS) or placebo on ADHD symptoms in 30 children whose manic symptoms stabilized on divalproex. MAS showed a significant, independent effect on ADHD symptoms One patient’s manic symptoms recurred during stimulant therapy and subsided with MAS discontinuation.
In this trial, mania symptoms responded to divalproex, whereas ADHD symptoms did not. MAS treatment showed a specific effect on ADHD symptoms of inattention, impulsivity, and hyperactivity. The shared symptoms of mania and ADHD (impulsivity and hyperactivity) decreased with divalproex to some extent.
Table 2
Pediatric mania and ADHD
respond differently to mood-stabilizer therapy
| Children with bipolar I or II disorder and concurrent ADHD | Treatment with divalproex, 8 weeks (N = 40)a | Subjects enter double-blind, crossover treatment with MAS and placebo, 2 weeks each (N = 30) | |
|---|---|---|---|
| Manic symptomsb | 32 of 40 (80%) improved; significant (P <0.0001) | MAS | Placebo |
| No significant change in manic symptoms (P = 0.17) | |||
| ADHD symptomsc | 3 of 40 (7.5%) improved; not significant (P = 0.96) | 26 of 30 (87%) improved | 3 of 30 (10%) improved |
| CGI scores improved 1.9 points more on MAS than on placebo, a significant difference (P <0.0001) | |||
| a Average divalproex blood levels = 82 μg/mL | |||
| b Manic symptom improvement defined as >50% decrease in baseline Young Mania Rating Scale scores | |||
| c ADHD symptom improvement defined as Clinical Global Impression (CGI)–Improvement scores of 1 or 2 | |||
| MAS: Mixed amphetamine salts | |||
| Source: Reference 7 | |||
WHEN MANIA/ADHD CO-OCCUR
ADHD and bipolar disorder symptoms overlap to a great extent, and the disorders can co-occur:
- Up to 20% of children diagnosed with ADHD also meet bipolar criteria.
- Two-thirds of children with bipolar disorder may also meet criteria for ADHD, with reports ranging from 29% to 98%.1,2
When trying to differentiate ADHD and bipolar disorder in children, consider the core symptoms of each diagnosis (Table 3).
Table 3
Core symptoms: Pediatric bipolar disorder vs ADHD
| Symptom | Bipolar disorder | ADHD |
|---|---|---|
| Euphoria/giddiness | Excessive | Appropriate to situations |
| Irritability | Severe and intense, often accompanied by tantrums | Occasional, may be caused by medication “wear-off” |
| Self-esteem | Grandiose | Demoralized |
| Sleep patterns | Decreased need for sleep | Difficulty settling at night |
| Speech patterns | Pressured, fragmented, with flight of ideas | Energetic and quick |
| Thought processes | Racing thoughts | Patients do not report racing thoughts |
| Psychosis can occur at times | ||
| Attention | Distractible | Distractible |
| Activity level | High energy, on-the-go, multiple projects, creative | Hyperactive, multiple projects |
| High-risk behaviors | Impulsive | |
| Disruptive behaviors | Can become aggressive | Intrusive and active |
Related resources
- Geller B, DelBello MP (eds). Bipolar disorder in childhood and early adolescence. New York: Guilford Press, 2003.
- Papolos DF, Papolos J. Bipolar child: The definitive and reassuring guide to childhood’s most misunderstood disorder. New York: Broadway Books, 2002.
- Fristad MA, Goldberg Arnold JS. Raising a moody child: How to cope with depression and bipolar disorder. New York: Guilford Press, 2003.
- Child and Adolescent Bipolar Foundation. Available at www.cabf.org. Accessed March 4, 2005.
Drug brand names
- Divalproex sodium • Depakote
- Mixed amphetamine salts • Adderall
Disclosures
Dr. Scheffer receives research support from and is a speaker for Abbott Laboratories.
Dr. Apps reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Wozniak J, Biederman J, Kiely K, et al. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry 1995;34(7):867-76.
2. Biederman J, Faraone S, Mick E, et al. Attention-deficit hyperactivity disorder and juvenile mania: an overlooked comorbidity? J Am Acad Child Adolesc Psychiatry 1996;35(8):997-1008.
3. Patel NC, Sallee FR. What’s the best treatment for ADHD/bipolar mania? Current Psychiatry 2005;3(3):27-37.
4. Geller B, Tillman R, Craney JL, Bolhofner K. Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype. Arch Gen Psychiatry 2004;61:459-67.
5. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed., rev). Washington, DC: American Psychiatric Association, 2000.
6. Geller B, Williams M, Zimerman B, et al. Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling. J Affect Disord 1998;51(2):81-91.
7. Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry 2005;162(1):58-64.
1. Wozniak J, Biederman J, Kiely K, et al. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry 1995;34(7):867-76.
2. Biederman J, Faraone S, Mick E, et al. Attention-deficit hyperactivity disorder and juvenile mania: an overlooked comorbidity? J Am Acad Child Adolesc Psychiatry 1996;35(8):997-1008.
3. Patel NC, Sallee FR. What’s the best treatment for ADHD/bipolar mania? Current Psychiatry 2005;3(3):27-37.
4. Geller B, Tillman R, Craney JL, Bolhofner K. Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype. Arch Gen Psychiatry 2004;61:459-67.
5. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed., rev). Washington, DC: American Psychiatric Association, 2000.
6. Geller B, Williams M, Zimerman B, et al. Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling. J Affect Disord 1998;51(2):81-91.
7. Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry 2005;162(1):58-64.
Understanding dreams: Tapping a rich resource
Dreams are a rich resource for understanding how the mind integrates waking experience into older memory networks. Any psychiatrist who doubts dreams’ therapeutic value has probably not attended closely to his or her own dreams or become aware of exciting new evidence.
Recent understandings of how memory is processed during sleep are bringing dreams back into clinical importance. Patients can gather clinically useful data while sleeping—not in laboratories but in their own beds. Detecting and interpreting patterns in that data can help you treat patients not responding adequately to other therapies.
CHARTING DREAM SEQUENCES
The rate at which the eyes move during rapid-eye movement (REM) sleep (Figure) has been associated with memory consolidation. Eye movements increase during REM sleep, and waking performance improves after intensive learning periods. When eye movements are sparse, patients report dreams with less visual imagery and blander emotional content.1
Though all sleep stages contribute to learning and memory, REM sleep appears to allow wider, easier access to memories2 than does slow-wave sleep or waking. In other words, dreams are far from meaningless. They constitute a continuing mental operation that allows us to modify memory networks of emotional importance to us.
Dreams’ emotional tone tends to shift from negative to positive as the night goes on:3
- Dream-to-dream down-regulation of negative feelings is seen when a person’s waking concerns are strong but not overwhelming.
- Conversely, a dream sequence may show no progress within the night4—and the last dream may be as negative as the first—if the person has reached a point of resignation while awake.
This “sequential hypothesis”5 holds that knowledge of dreams as they occur—one after the other within the night—is a valuable resource for observing how a person is relating waking experience to the past. Dreams thus can give the therapist a “heads up” about a patient’s progress in organizing troublesome feelings.
Figure REM sleep: Dreaming’s prime time
CASE EXAMPLE: NIGHTMARES FOR 13 YEARS
Ms. R, a newlywed at age 30, presents for help with repetitive nightmares that prevent her from sharing a bed with her husband. She was raped at age 17 and has suffered nightmares since then. Once or more nightly she dreams of being attacked and awakens in terror, with profuse sweating. She usually has to change her nightclothes and sometimes the sheets.
Her therapist gives Ms. R four rules—the RISC method6—for shifting her dreams from negative to positive:
- Recognize that the dream is not going well.
- Identify what about it is frightening.
- Stop the dream, even if she must force her eyes open.
- Change the action to something positive.
At the third therapy session, Ms. R reports she had a successful dream. She was lying on her back on an open elevator platform. The elevator was rising dangerously high over the cityscape. She realized she was afraid and got up to see what was happening. As she arose, the elevator walls rose up to protect her. The patient says she learned if she “stands up for herself” all would be well.
After two more sessions with successful practice of this skill, she terminates therapy. When called 1 year later, she says she is expecting a child and has only an occasional nightmare, which she feels she can handle.
CLINICAL USES OF DREAM THERAPY
Dream interpretation may help us understand emotional programs that underlie patients’ unsatisfactory waking behavior. For example:
- Victims of posttraumatic stress disorder (PTSD) such as Ms. R may suffer repetitive nightmares with recurrent themes and excessive negative feelings. We can encourage them to shift their dream scripts from negative to positive.7
- Uninsightful, alexythymic patients, who often leave treatment before deriving any benefit, may learn to understand themselves by becoming aware of their dreams.8
- Severely depressed patientsoften have limited dream recall during sleep studies—even when every REM period is interrupted. They may be taught to improve their dream recall.9
Rules for improving dream recall are few, simple, and effective when the sleeper is motivated to remember them (Box). Just as one can learn to awaken before the morning alarm clock goes off, patients can learn to awaken to recall a dream.
After you have enough of a patient’s dreams to work from—20 is a good start—look for repeated dimensions that are the dreams’ building blocks.5 Look for polar opposites—such as safe-at risk, foolish-clever, exposed-hidden, strong-weak, attractive-ugly—that describe major characteristics of the self figure. Each has a positive or negative emotional value that can be explored.
Go to sleep intending to remember a dream as you awaken.
Sleep until you wake up naturally.* Spontaneous awakening is likely to be from REM sleep, which is dominant in the last third of the night.
Once awake, lie perfectly still. Do not jump up or open your eyes. This preserves a REM-like state when attention is focused inward, not on outside stimuli, and motor tone is profoundly reduced.
Rehearse the recalled images, and give the theme a title (“I left my briefcase on the train” or “My husband returned from a trip unexpectedly”), which makes dream details easier to recall.
Write or tape record all that you can remember, noting the date and time of the report.
Add a note about anything the dream brings to mind about your thoughts before sleep.
* To allow spontaneous awakening, practice dream recall when you do not have to wake up to an alarm clock, such as on weekends.
WHAT TURNED US OFF ABOUT DREAMS
Prolonged therapy. Freud’s The Interpretation of Dreams 10 was a major influence on how therapists used dreams to understand their patients in the early 20th century. Freud concluded that dreams —however strange—represent hallucinated fulfillment of repressed early wishes and tie up psychic energy to conceal unacceptable desires.
From this point of view, dreams provide a road map to understand persistent, nonrational, sometimes self-defeating behaviors that bring patients to therapy. The map, however, was more maze than speedway, full of detours and requiring much time to navigate the boulevards of associations that lead from one dream element to the next. Erik Erickson11 suggested that dreams fell into disuse as therapeutic tools in the 1930s because psychoanalysis in general—and dream interpretation in particular—did not fit the American value of “the faster the better.”
In retrospect, the unconscious mind’s defenses may not have been what prolonged efforts to understand dream meaning. Rather, it may have been that the analyst had to work from whatever scraps the patient could remember of past dreams, to say nothing of new ones that occurred since the last appointment. That one dream could occupy many treatment hours did not trouble the Freudians, however, as—they argued—any-thing the patient does remember is proof of its importance.
Sleep research dealt the worst blow to the pursuit of dreams’ meaning and function.12,13 Contrary to Freud’s view, dreams are not elusive if caught in the act. They can be reliably retrieved from REM episodes, which occur three to five times nightly with great regularity.
After REM sleep was found to initiate from the “unthinking pons,” dreams were proclaimed to have no inherent meaning worthy of serious effort. At best, they were explained as the result of random stimuli producing images to which we add meaning as we awaken. Thus, they offer no unique contribution to understanding psychic life. This “activation-synthesis” hypothesis14 wiped out dream research funding.
Medications. The pharmacologic revolution allowed more-rapid relief of anxiety and depression symptoms than did dream interpretation. Clinicians may feel that “we can forget about dreams because we now have better options.” This ignores research showing that psychiatric medication plus psychotherapy is more effective for a longer time than either alone.15
Evidence-based medicine. Dream content is inherently subjective and not open to objective observation, the heart of scientific methods. Only the dreamer can say what was dreamed.
WHAT BROUGHT DREAMS BACK
Better methods and more-sophisticated models renewed dream interpretation as a useful adjunct to other psychotherapies. In addition to research in memory processing, imaging methods and neuropsychological testing have changed our understanding of brain activity during sleep.
Brain imaging. Early sleep study was limited to recordings from the scalp surface. Now positron emission tomography and functional magnetic imagery allow researchers to see changes in brain activity and to study patterns during waking, non-REM sleep, and REM sleep and among clinical groups. Nofzinger et al,16 for example, showed differences in areas of high and low brain activation in persons with major depression, compared with normal controls.
Neuropsychological testing. Solms2 used neuropsychological testing and interviewing to identify waking cognitive deficits and changes in dream experience in persons with brain damage from surgery or accident. Contrary to the “activation-synthesis” model, he concluded that dreams “are both generated and represented by some of the highest mental mechanisms.” He also argued that although dreams often coincide with the REM state, they also occur beyond REM.
COMING SOON: AT-HOME SLEEP MONITORS
In a sleep laboratory, awakening sleepers during REM periods and asking them to tell what they remember is the classic method for examining the relation among a night’s dreams.17-19 This cumbersome and expensive procedure is being simplified for home use.
Computer-linked monitors are being developed that awaken the sleeper after a pre-set number of rapid eye movements and start a tape recorder to which the person can tell his or her dream. This system, which preserves the dream story from memory loss or distortion,20,21 can easily record three or four dreams each night.
Translating this sensory data into verbal reports remains difficult. Although repeated elements give clues to dream structure, a repeated theme within a night might be an artifact induced by waking the sleeper to ask for a report. If a sleeper reports dreaming about being in an accident, for example, he may be influenced to continue that line of thought as he is falling back to sleep. This, in turn, may influence the next dream.
What else can we do? Because dream recall is ephemeral at best, patients may need training before a therapist has a sample large enough to extract repeating elements and be confident of its reliability.
Related resources
- Schneider A, Domhoff GW. Psychology department, University of California, Santa Cruz. Web site for collecting dream reports. www.DreamBank.net.
- American Psychological Association. Dreaming. Quarterly multidisciplinary journal. www.apa.org/journals/drm/.
Disclosures
The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Pivik R. Tonic states and phasic events in relation to sleep mentation. In: Ellman S, Antrobus J (eds). The mind in sleep. New York: John Wiley and Sons, 1991;214-47.
2. Solms M. The neuropsychology of dreams. Mahwah, NJ: Lawrence Erlbaum Associates; 1997.
3. Cartwright R, Luten A, Young M, et al. Role of REM sleep and dream affect in overnight mood regulation: a study of normals. Psychiatry Res 1998a;81:1-8.
4. Cartwright R, Young M, Mercer P, Bears M. Role of REM sleep and dream variables in the prediction of remission from depression. Psychiatry Res 1998b;80:249-55.
5. Giuditta A, Mandile P, Montagnese P, et al. The role of sleep in memory processing: the sequential hypothesis. In: Maquet P, Smith C, Stickgold R (eds). Sleep and brain plasticity. Oxford, UK: Oxford University Press; 2003.
6. Cartwright R, Lamberg L. Crisis dreaming. New York: Harper Collins; 1993;42-51.
7. Armitage R, Rochlen A, Fitch T, et al. Dream recall and major depression: a preliminary report. Dreaming 1995;5:189-98.
8. Cartwright R, Tipton L, Wicklund J. Focusing on dreams: a preparation program for psychotherapy. Arch Gen Psychiatry 1980;37:275-7.
9. Riemann D, Wiegand M, Majer-Trendal K, et al. Dream recall and dream content in depressive patients, patients with anorexia nervosa and normal controls. In: Koella W, Obal F, Schulz H, Viss P (eds). Sleep ’86. Stuttgart: Gustav Fischer; 1988;373-6.
10. Freud S. The interpretation of dreams. New York: Basic Books; 1955.
11. Erickson E. The dream specimen in psychoanalysis. In: Knight R, Friedman C (eds). Psychoanalytic psychiatry and psychology. New York: International Press; 1954.
12. Aserinsky E, Kleitman N. Regularly occurring periods of eye motility and concomitant phenomena during sleep. Science 1953;118:273.-
13. Dement W, Kleitman N. Relation of eye movements during sleep to dream activity: objective method for the study of dreaming. J Exper Psychol 1957;53:339-46.
14. Hobson JA, McCarley R. The brain as a dream state generator: An activation-synthesis hypothesis of the dream process. Am J Psychiatry 1977;134:1335-48.
15. Weissman M, Klerman G, Prusoff B, et al. Depressed outpatients one year after treatment with drugs and/or interpersonal psychotherapy. Arch Gen Psychiatry 1981;38:51-5.
16. Nofzinger E, Buysse D, Germain A, et al. Increased activation of anterior paralimbic and executive cortex from waking to rapid eye movement sleep in depression. Arch Gen Psychiatry 2004;61:695-702.
17. Rechtschaffen A, Vogel G, Shaikun G. Interrelatedness of mental activity during sleep. Arch Gen Psychiatry 1963;9:536-47.
18. Verdone P. Temporal reference of manifest dream content. Percept Motor Skills 1965;20:1253.-
18. Cartwright R. Night life: explorations in dreaming. Englewood Cliffs, NJ: Prentice-Hall; 1977;18-31.
20. Mamelak A, Hobson JA. Nightcap: a home-based sleep monitoring system. Sleep 1989;12:157-66.
21. Lloyd S, Cartwright R. The collection of home and laboratory dreams by means of an instrumental response technique. Dreaming 1995;5:63-73.
Dreams are a rich resource for understanding how the mind integrates waking experience into older memory networks. Any psychiatrist who doubts dreams’ therapeutic value has probably not attended closely to his or her own dreams or become aware of exciting new evidence.
Recent understandings of how memory is processed during sleep are bringing dreams back into clinical importance. Patients can gather clinically useful data while sleeping—not in laboratories but in their own beds. Detecting and interpreting patterns in that data can help you treat patients not responding adequately to other therapies.
CHARTING DREAM SEQUENCES
The rate at which the eyes move during rapid-eye movement (REM) sleep (Figure) has been associated with memory consolidation. Eye movements increase during REM sleep, and waking performance improves after intensive learning periods. When eye movements are sparse, patients report dreams with less visual imagery and blander emotional content.1
Though all sleep stages contribute to learning and memory, REM sleep appears to allow wider, easier access to memories2 than does slow-wave sleep or waking. In other words, dreams are far from meaningless. They constitute a continuing mental operation that allows us to modify memory networks of emotional importance to us.
Dreams’ emotional tone tends to shift from negative to positive as the night goes on:3
- Dream-to-dream down-regulation of negative feelings is seen when a person’s waking concerns are strong but not overwhelming.
- Conversely, a dream sequence may show no progress within the night4—and the last dream may be as negative as the first—if the person has reached a point of resignation while awake.
This “sequential hypothesis”5 holds that knowledge of dreams as they occur—one after the other within the night—is a valuable resource for observing how a person is relating waking experience to the past. Dreams thus can give the therapist a “heads up” about a patient’s progress in organizing troublesome feelings.
Figure REM sleep: Dreaming’s prime time
CASE EXAMPLE: NIGHTMARES FOR 13 YEARS
Ms. R, a newlywed at age 30, presents for help with repetitive nightmares that prevent her from sharing a bed with her husband. She was raped at age 17 and has suffered nightmares since then. Once or more nightly she dreams of being attacked and awakens in terror, with profuse sweating. She usually has to change her nightclothes and sometimes the sheets.
Her therapist gives Ms. R four rules—the RISC method6—for shifting her dreams from negative to positive:
- Recognize that the dream is not going well.
- Identify what about it is frightening.
- Stop the dream, even if she must force her eyes open.
- Change the action to something positive.
At the third therapy session, Ms. R reports she had a successful dream. She was lying on her back on an open elevator platform. The elevator was rising dangerously high over the cityscape. She realized she was afraid and got up to see what was happening. As she arose, the elevator walls rose up to protect her. The patient says she learned if she “stands up for herself” all would be well.
After two more sessions with successful practice of this skill, she terminates therapy. When called 1 year later, she says she is expecting a child and has only an occasional nightmare, which she feels she can handle.
CLINICAL USES OF DREAM THERAPY
Dream interpretation may help us understand emotional programs that underlie patients’ unsatisfactory waking behavior. For example:
- Victims of posttraumatic stress disorder (PTSD) such as Ms. R may suffer repetitive nightmares with recurrent themes and excessive negative feelings. We can encourage them to shift their dream scripts from negative to positive.7
- Uninsightful, alexythymic patients, who often leave treatment before deriving any benefit, may learn to understand themselves by becoming aware of their dreams.8
- Severely depressed patientsoften have limited dream recall during sleep studies—even when every REM period is interrupted. They may be taught to improve their dream recall.9
Rules for improving dream recall are few, simple, and effective when the sleeper is motivated to remember them (Box). Just as one can learn to awaken before the morning alarm clock goes off, patients can learn to awaken to recall a dream.
After you have enough of a patient’s dreams to work from—20 is a good start—look for repeated dimensions that are the dreams’ building blocks.5 Look for polar opposites—such as safe-at risk, foolish-clever, exposed-hidden, strong-weak, attractive-ugly—that describe major characteristics of the self figure. Each has a positive or negative emotional value that can be explored.
Go to sleep intending to remember a dream as you awaken.
Sleep until you wake up naturally.* Spontaneous awakening is likely to be from REM sleep, which is dominant in the last third of the night.
Once awake, lie perfectly still. Do not jump up or open your eyes. This preserves a REM-like state when attention is focused inward, not on outside stimuli, and motor tone is profoundly reduced.
Rehearse the recalled images, and give the theme a title (“I left my briefcase on the train” or “My husband returned from a trip unexpectedly”), which makes dream details easier to recall.
Write or tape record all that you can remember, noting the date and time of the report.
Add a note about anything the dream brings to mind about your thoughts before sleep.
* To allow spontaneous awakening, practice dream recall when you do not have to wake up to an alarm clock, such as on weekends.
WHAT TURNED US OFF ABOUT DREAMS
Prolonged therapy. Freud’s The Interpretation of Dreams 10 was a major influence on how therapists used dreams to understand their patients in the early 20th century. Freud concluded that dreams —however strange—represent hallucinated fulfillment of repressed early wishes and tie up psychic energy to conceal unacceptable desires.
From this point of view, dreams provide a road map to understand persistent, nonrational, sometimes self-defeating behaviors that bring patients to therapy. The map, however, was more maze than speedway, full of detours and requiring much time to navigate the boulevards of associations that lead from one dream element to the next. Erik Erickson11 suggested that dreams fell into disuse as therapeutic tools in the 1930s because psychoanalysis in general—and dream interpretation in particular—did not fit the American value of “the faster the better.”
In retrospect, the unconscious mind’s defenses may not have been what prolonged efforts to understand dream meaning. Rather, it may have been that the analyst had to work from whatever scraps the patient could remember of past dreams, to say nothing of new ones that occurred since the last appointment. That one dream could occupy many treatment hours did not trouble the Freudians, however, as—they argued—any-thing the patient does remember is proof of its importance.
Sleep research dealt the worst blow to the pursuit of dreams’ meaning and function.12,13 Contrary to Freud’s view, dreams are not elusive if caught in the act. They can be reliably retrieved from REM episodes, which occur three to five times nightly with great regularity.
After REM sleep was found to initiate from the “unthinking pons,” dreams were proclaimed to have no inherent meaning worthy of serious effort. At best, they were explained as the result of random stimuli producing images to which we add meaning as we awaken. Thus, they offer no unique contribution to understanding psychic life. This “activation-synthesis” hypothesis14 wiped out dream research funding.
Medications. The pharmacologic revolution allowed more-rapid relief of anxiety and depression symptoms than did dream interpretation. Clinicians may feel that “we can forget about dreams because we now have better options.” This ignores research showing that psychiatric medication plus psychotherapy is more effective for a longer time than either alone.15
Evidence-based medicine. Dream content is inherently subjective and not open to objective observation, the heart of scientific methods. Only the dreamer can say what was dreamed.
WHAT BROUGHT DREAMS BACK
Better methods and more-sophisticated models renewed dream interpretation as a useful adjunct to other psychotherapies. In addition to research in memory processing, imaging methods and neuropsychological testing have changed our understanding of brain activity during sleep.
Brain imaging. Early sleep study was limited to recordings from the scalp surface. Now positron emission tomography and functional magnetic imagery allow researchers to see changes in brain activity and to study patterns during waking, non-REM sleep, and REM sleep and among clinical groups. Nofzinger et al,16 for example, showed differences in areas of high and low brain activation in persons with major depression, compared with normal controls.
Neuropsychological testing. Solms2 used neuropsychological testing and interviewing to identify waking cognitive deficits and changes in dream experience in persons with brain damage from surgery or accident. Contrary to the “activation-synthesis” model, he concluded that dreams “are both generated and represented by some of the highest mental mechanisms.” He also argued that although dreams often coincide with the REM state, they also occur beyond REM.
COMING SOON: AT-HOME SLEEP MONITORS
In a sleep laboratory, awakening sleepers during REM periods and asking them to tell what they remember is the classic method for examining the relation among a night’s dreams.17-19 This cumbersome and expensive procedure is being simplified for home use.
Computer-linked monitors are being developed that awaken the sleeper after a pre-set number of rapid eye movements and start a tape recorder to which the person can tell his or her dream. This system, which preserves the dream story from memory loss or distortion,20,21 can easily record three or four dreams each night.
Translating this sensory data into verbal reports remains difficult. Although repeated elements give clues to dream structure, a repeated theme within a night might be an artifact induced by waking the sleeper to ask for a report. If a sleeper reports dreaming about being in an accident, for example, he may be influenced to continue that line of thought as he is falling back to sleep. This, in turn, may influence the next dream.
What else can we do? Because dream recall is ephemeral at best, patients may need training before a therapist has a sample large enough to extract repeating elements and be confident of its reliability.
Related resources
- Schneider A, Domhoff GW. Psychology department, University of California, Santa Cruz. Web site for collecting dream reports. www.DreamBank.net.
- American Psychological Association. Dreaming. Quarterly multidisciplinary journal. www.apa.org/journals/drm/.
Disclosures
The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dreams are a rich resource for understanding how the mind integrates waking experience into older memory networks. Any psychiatrist who doubts dreams’ therapeutic value has probably not attended closely to his or her own dreams or become aware of exciting new evidence.
Recent understandings of how memory is processed during sleep are bringing dreams back into clinical importance. Patients can gather clinically useful data while sleeping—not in laboratories but in their own beds. Detecting and interpreting patterns in that data can help you treat patients not responding adequately to other therapies.
CHARTING DREAM SEQUENCES
The rate at which the eyes move during rapid-eye movement (REM) sleep (Figure) has been associated with memory consolidation. Eye movements increase during REM sleep, and waking performance improves after intensive learning periods. When eye movements are sparse, patients report dreams with less visual imagery and blander emotional content.1
Though all sleep stages contribute to learning and memory, REM sleep appears to allow wider, easier access to memories2 than does slow-wave sleep or waking. In other words, dreams are far from meaningless. They constitute a continuing mental operation that allows us to modify memory networks of emotional importance to us.
Dreams’ emotional tone tends to shift from negative to positive as the night goes on:3
- Dream-to-dream down-regulation of negative feelings is seen when a person’s waking concerns are strong but not overwhelming.
- Conversely, a dream sequence may show no progress within the night4—and the last dream may be as negative as the first—if the person has reached a point of resignation while awake.
This “sequential hypothesis”5 holds that knowledge of dreams as they occur—one after the other within the night—is a valuable resource for observing how a person is relating waking experience to the past. Dreams thus can give the therapist a “heads up” about a patient’s progress in organizing troublesome feelings.
Figure REM sleep: Dreaming’s prime time
CASE EXAMPLE: NIGHTMARES FOR 13 YEARS
Ms. R, a newlywed at age 30, presents for help with repetitive nightmares that prevent her from sharing a bed with her husband. She was raped at age 17 and has suffered nightmares since then. Once or more nightly she dreams of being attacked and awakens in terror, with profuse sweating. She usually has to change her nightclothes and sometimes the sheets.
Her therapist gives Ms. R four rules—the RISC method6—for shifting her dreams from negative to positive:
- Recognize that the dream is not going well.
- Identify what about it is frightening.
- Stop the dream, even if she must force her eyes open.
- Change the action to something positive.
At the third therapy session, Ms. R reports she had a successful dream. She was lying on her back on an open elevator platform. The elevator was rising dangerously high over the cityscape. She realized she was afraid and got up to see what was happening. As she arose, the elevator walls rose up to protect her. The patient says she learned if she “stands up for herself” all would be well.
After two more sessions with successful practice of this skill, she terminates therapy. When called 1 year later, she says she is expecting a child and has only an occasional nightmare, which she feels she can handle.
CLINICAL USES OF DREAM THERAPY
Dream interpretation may help us understand emotional programs that underlie patients’ unsatisfactory waking behavior. For example:
- Victims of posttraumatic stress disorder (PTSD) such as Ms. R may suffer repetitive nightmares with recurrent themes and excessive negative feelings. We can encourage them to shift their dream scripts from negative to positive.7
- Uninsightful, alexythymic patients, who often leave treatment before deriving any benefit, may learn to understand themselves by becoming aware of their dreams.8
- Severely depressed patientsoften have limited dream recall during sleep studies—even when every REM period is interrupted. They may be taught to improve their dream recall.9
Rules for improving dream recall are few, simple, and effective when the sleeper is motivated to remember them (Box). Just as one can learn to awaken before the morning alarm clock goes off, patients can learn to awaken to recall a dream.
After you have enough of a patient’s dreams to work from—20 is a good start—look for repeated dimensions that are the dreams’ building blocks.5 Look for polar opposites—such as safe-at risk, foolish-clever, exposed-hidden, strong-weak, attractive-ugly—that describe major characteristics of the self figure. Each has a positive or negative emotional value that can be explored.
Go to sleep intending to remember a dream as you awaken.
Sleep until you wake up naturally.* Spontaneous awakening is likely to be from REM sleep, which is dominant in the last third of the night.
Once awake, lie perfectly still. Do not jump up or open your eyes. This preserves a REM-like state when attention is focused inward, not on outside stimuli, and motor tone is profoundly reduced.
Rehearse the recalled images, and give the theme a title (“I left my briefcase on the train” or “My husband returned from a trip unexpectedly”), which makes dream details easier to recall.
Write or tape record all that you can remember, noting the date and time of the report.
Add a note about anything the dream brings to mind about your thoughts before sleep.
* To allow spontaneous awakening, practice dream recall when you do not have to wake up to an alarm clock, such as on weekends.
WHAT TURNED US OFF ABOUT DREAMS
Prolonged therapy. Freud’s The Interpretation of Dreams 10 was a major influence on how therapists used dreams to understand their patients in the early 20th century. Freud concluded that dreams —however strange—represent hallucinated fulfillment of repressed early wishes and tie up psychic energy to conceal unacceptable desires.
From this point of view, dreams provide a road map to understand persistent, nonrational, sometimes self-defeating behaviors that bring patients to therapy. The map, however, was more maze than speedway, full of detours and requiring much time to navigate the boulevards of associations that lead from one dream element to the next. Erik Erickson11 suggested that dreams fell into disuse as therapeutic tools in the 1930s because psychoanalysis in general—and dream interpretation in particular—did not fit the American value of “the faster the better.”
In retrospect, the unconscious mind’s defenses may not have been what prolonged efforts to understand dream meaning. Rather, it may have been that the analyst had to work from whatever scraps the patient could remember of past dreams, to say nothing of new ones that occurred since the last appointment. That one dream could occupy many treatment hours did not trouble the Freudians, however, as—they argued—any-thing the patient does remember is proof of its importance.
Sleep research dealt the worst blow to the pursuit of dreams’ meaning and function.12,13 Contrary to Freud’s view, dreams are not elusive if caught in the act. They can be reliably retrieved from REM episodes, which occur three to five times nightly with great regularity.
After REM sleep was found to initiate from the “unthinking pons,” dreams were proclaimed to have no inherent meaning worthy of serious effort. At best, they were explained as the result of random stimuli producing images to which we add meaning as we awaken. Thus, they offer no unique contribution to understanding psychic life. This “activation-synthesis” hypothesis14 wiped out dream research funding.
Medications. The pharmacologic revolution allowed more-rapid relief of anxiety and depression symptoms than did dream interpretation. Clinicians may feel that “we can forget about dreams because we now have better options.” This ignores research showing that psychiatric medication plus psychotherapy is more effective for a longer time than either alone.15
Evidence-based medicine. Dream content is inherently subjective and not open to objective observation, the heart of scientific methods. Only the dreamer can say what was dreamed.
WHAT BROUGHT DREAMS BACK
Better methods and more-sophisticated models renewed dream interpretation as a useful adjunct to other psychotherapies. In addition to research in memory processing, imaging methods and neuropsychological testing have changed our understanding of brain activity during sleep.
Brain imaging. Early sleep study was limited to recordings from the scalp surface. Now positron emission tomography and functional magnetic imagery allow researchers to see changes in brain activity and to study patterns during waking, non-REM sleep, and REM sleep and among clinical groups. Nofzinger et al,16 for example, showed differences in areas of high and low brain activation in persons with major depression, compared with normal controls.
Neuropsychological testing. Solms2 used neuropsychological testing and interviewing to identify waking cognitive deficits and changes in dream experience in persons with brain damage from surgery or accident. Contrary to the “activation-synthesis” model, he concluded that dreams “are both generated and represented by some of the highest mental mechanisms.” He also argued that although dreams often coincide with the REM state, they also occur beyond REM.
COMING SOON: AT-HOME SLEEP MONITORS
In a sleep laboratory, awakening sleepers during REM periods and asking them to tell what they remember is the classic method for examining the relation among a night’s dreams.17-19 This cumbersome and expensive procedure is being simplified for home use.
Computer-linked monitors are being developed that awaken the sleeper after a pre-set number of rapid eye movements and start a tape recorder to which the person can tell his or her dream. This system, which preserves the dream story from memory loss or distortion,20,21 can easily record three or four dreams each night.
Translating this sensory data into verbal reports remains difficult. Although repeated elements give clues to dream structure, a repeated theme within a night might be an artifact induced by waking the sleeper to ask for a report. If a sleeper reports dreaming about being in an accident, for example, he may be influenced to continue that line of thought as he is falling back to sleep. This, in turn, may influence the next dream.
What else can we do? Because dream recall is ephemeral at best, patients may need training before a therapist has a sample large enough to extract repeating elements and be confident of its reliability.
Related resources
- Schneider A, Domhoff GW. Psychology department, University of California, Santa Cruz. Web site for collecting dream reports. www.DreamBank.net.
- American Psychological Association. Dreaming. Quarterly multidisciplinary journal. www.apa.org/journals/drm/.
Disclosures
The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Pivik R. Tonic states and phasic events in relation to sleep mentation. In: Ellman S, Antrobus J (eds). The mind in sleep. New York: John Wiley and Sons, 1991;214-47.
2. Solms M. The neuropsychology of dreams. Mahwah, NJ: Lawrence Erlbaum Associates; 1997.
3. Cartwright R, Luten A, Young M, et al. Role of REM sleep and dream affect in overnight mood regulation: a study of normals. Psychiatry Res 1998a;81:1-8.
4. Cartwright R, Young M, Mercer P, Bears M. Role of REM sleep and dream variables in the prediction of remission from depression. Psychiatry Res 1998b;80:249-55.
5. Giuditta A, Mandile P, Montagnese P, et al. The role of sleep in memory processing: the sequential hypothesis. In: Maquet P, Smith C, Stickgold R (eds). Sleep and brain plasticity. Oxford, UK: Oxford University Press; 2003.
6. Cartwright R, Lamberg L. Crisis dreaming. New York: Harper Collins; 1993;42-51.
7. Armitage R, Rochlen A, Fitch T, et al. Dream recall and major depression: a preliminary report. Dreaming 1995;5:189-98.
8. Cartwright R, Tipton L, Wicklund J. Focusing on dreams: a preparation program for psychotherapy. Arch Gen Psychiatry 1980;37:275-7.
9. Riemann D, Wiegand M, Majer-Trendal K, et al. Dream recall and dream content in depressive patients, patients with anorexia nervosa and normal controls. In: Koella W, Obal F, Schulz H, Viss P (eds). Sleep ’86. Stuttgart: Gustav Fischer; 1988;373-6.
10. Freud S. The interpretation of dreams. New York: Basic Books; 1955.
11. Erickson E. The dream specimen in psychoanalysis. In: Knight R, Friedman C (eds). Psychoanalytic psychiatry and psychology. New York: International Press; 1954.
12. Aserinsky E, Kleitman N. Regularly occurring periods of eye motility and concomitant phenomena during sleep. Science 1953;118:273.-
13. Dement W, Kleitman N. Relation of eye movements during sleep to dream activity: objective method for the study of dreaming. J Exper Psychol 1957;53:339-46.
14. Hobson JA, McCarley R. The brain as a dream state generator: An activation-synthesis hypothesis of the dream process. Am J Psychiatry 1977;134:1335-48.
15. Weissman M, Klerman G, Prusoff B, et al. Depressed outpatients one year after treatment with drugs and/or interpersonal psychotherapy. Arch Gen Psychiatry 1981;38:51-5.
16. Nofzinger E, Buysse D, Germain A, et al. Increased activation of anterior paralimbic and executive cortex from waking to rapid eye movement sleep in depression. Arch Gen Psychiatry 2004;61:695-702.
17. Rechtschaffen A, Vogel G, Shaikun G. Interrelatedness of mental activity during sleep. Arch Gen Psychiatry 1963;9:536-47.
18. Verdone P. Temporal reference of manifest dream content. Percept Motor Skills 1965;20:1253.-
18. Cartwright R. Night life: explorations in dreaming. Englewood Cliffs, NJ: Prentice-Hall; 1977;18-31.
20. Mamelak A, Hobson JA. Nightcap: a home-based sleep monitoring system. Sleep 1989;12:157-66.
21. Lloyd S, Cartwright R. The collection of home and laboratory dreams by means of an instrumental response technique. Dreaming 1995;5:63-73.
1. Pivik R. Tonic states and phasic events in relation to sleep mentation. In: Ellman S, Antrobus J (eds). The mind in sleep. New York: John Wiley and Sons, 1991;214-47.
2. Solms M. The neuropsychology of dreams. Mahwah, NJ: Lawrence Erlbaum Associates; 1997.
3. Cartwright R, Luten A, Young M, et al. Role of REM sleep and dream affect in overnight mood regulation: a study of normals. Psychiatry Res 1998a;81:1-8.
4. Cartwright R, Young M, Mercer P, Bears M. Role of REM sleep and dream variables in the prediction of remission from depression. Psychiatry Res 1998b;80:249-55.
5. Giuditta A, Mandile P, Montagnese P, et al. The role of sleep in memory processing: the sequential hypothesis. In: Maquet P, Smith C, Stickgold R (eds). Sleep and brain plasticity. Oxford, UK: Oxford University Press; 2003.
6. Cartwright R, Lamberg L. Crisis dreaming. New York: Harper Collins; 1993;42-51.
7. Armitage R, Rochlen A, Fitch T, et al. Dream recall and major depression: a preliminary report. Dreaming 1995;5:189-98.
8. Cartwright R, Tipton L, Wicklund J. Focusing on dreams: a preparation program for psychotherapy. Arch Gen Psychiatry 1980;37:275-7.
9. Riemann D, Wiegand M, Majer-Trendal K, et al. Dream recall and dream content in depressive patients, patients with anorexia nervosa and normal controls. In: Koella W, Obal F, Schulz H, Viss P (eds). Sleep ’86. Stuttgart: Gustav Fischer; 1988;373-6.
10. Freud S. The interpretation of dreams. New York: Basic Books; 1955.
11. Erickson E. The dream specimen in psychoanalysis. In: Knight R, Friedman C (eds). Psychoanalytic psychiatry and psychology. New York: International Press; 1954.
12. Aserinsky E, Kleitman N. Regularly occurring periods of eye motility and concomitant phenomena during sleep. Science 1953;118:273.-
13. Dement W, Kleitman N. Relation of eye movements during sleep to dream activity: objective method for the study of dreaming. J Exper Psychol 1957;53:339-46.
14. Hobson JA, McCarley R. The brain as a dream state generator: An activation-synthesis hypothesis of the dream process. Am J Psychiatry 1977;134:1335-48.
15. Weissman M, Klerman G, Prusoff B, et al. Depressed outpatients one year after treatment with drugs and/or interpersonal psychotherapy. Arch Gen Psychiatry 1981;38:51-5.
16. Nofzinger E, Buysse D, Germain A, et al. Increased activation of anterior paralimbic and executive cortex from waking to rapid eye movement sleep in depression. Arch Gen Psychiatry 2004;61:695-702.
17. Rechtschaffen A, Vogel G, Shaikun G. Interrelatedness of mental activity during sleep. Arch Gen Psychiatry 1963;9:536-47.
18. Verdone P. Temporal reference of manifest dream content. Percept Motor Skills 1965;20:1253.-
18. Cartwright R. Night life: explorations in dreaming. Englewood Cliffs, NJ: Prentice-Hall; 1977;18-31.
20. Mamelak A, Hobson JA. Nightcap: a home-based sleep monitoring system. Sleep 1989;12:157-66.
21. Lloyd S, Cartwright R. The collection of home and laboratory dreams by means of an instrumental response technique. Dreaming 1995;5:63-73.
Treating OCD in patients with psychiatric comorbidity
Psychiatric comorbidities complicate the treatment of obsessive-compulsive disorder (OCD) and are much more the rule than the exception in clinical practice (Table 1).1-6 Even so, surprisingly few studies have examined comorbidities’ effects on OCD treatment, and results have been mixed.
For the typical patient with obsessive-compulsive symptoms, we discuss our experience and evidence that supports:
- clinically useful tools to differentiate OCD from other obsessive and anxiety disorders
- how to address comorbidities that pose acute danger or would prevent effective psychotherapy
- how to modify first-line OCD treatments—cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs)7-9—to also manage most comorbid disorders.
Table 1
Common psychiatric comorbidities with OCD
| Comorbidities | Estimated prevalence in OCD patients |
|---|---|
| Personality disorders | 63% |
| Major depressive disorder | 28 to 31% |
| Simple phobia | 7 to 48% |
| Social phobia | 11 to 16% |
| Bipolar disorder | 15% |
| Eating disorders | 8 to 13% |
| Alcohol abuse | 8% |
| Panic disorder | 6 to 12% |
| Tourette’s syndrome or tic disorders | 6 to 7% |
| Source: Data from references 1-6 | |
IS OCD PRIMARY?
OCD-like obsessive thoughts or repetitive behaviors may be evident in a number of psychiatric disorders. Distinguishing OCD from masquerading or co-occurring conditions is important because interventions can differ.
Patients with generalized anxiety disorder (GAD), for example, may experience ruminative, anxious thoughts that mimic obsessions. Somatoform conditions such as hypochondriasis or body dysmorphic disorder are characterized by intense preoccupation with illness or appearance, respectively. Repetitive or compulsive behaviors may be seen in impulse control or developmental disorders such as pathologic gambling, trichotillomania, and Asperger’s disorder.
To help differentiate OCD from these conditions, consider the function of a patient’s symptoms. In OCD, obsessions are experienced as ego-dystonic and generally cause great anxiety. OCD patients perform compulsive rituals to alleviate anxiety but do not gain pleasure from their actions. Contrast this with trichotillomania’s repetitive behavior—commonly experienced as pleasurable or gratifying—or with GAD’s ruminative thoughts—seen as ego-syntonic worries about real-life situations.
ASSESSING OCD, COMORBID CONDITIONS
When you suspect psychiatric comorbidity with OCD, an accurate and thorough assessment is key to successful treatment (Table 2).10-14
In specialty OCD clinics, the Structured Clinical Interview for DSM-IV (SCID-IV)15 or Anxiety Disorders Interview Schedule for the DSM-IV (ADIS-IV)10 are routinely given to assess the most common comorbid conditions. In clinical practice, however, these instruments can take up to several hours to perform, especially for patients who meet criteria for several disorders.
An alternative may be the Mini International Neuropsychiatric Interview (MINI).11 The MINI is a short, structured, diagnostic interview for DSM-IV and ICD-10 that takes about 15 minutes and screens for most conditions commonly comorbid with OCD. The MINI provides less-detailed information than the SCID-IV or the ADIS-IV but allows for a quick, accurate diagnosis while using a structured format.
Table 2
Common assessment tools for patients with suspected OCD
| Structured clinical interviews | Time to administer | Use |
|---|---|---|
| Anxiety Disorders Interview Schedule-IV (ADIS-IV) | 2+ hrs | Detailed assessment of anxiety disorders |
| Mini-International Neuropsychiatric Interview (MINI) | 15 to 30 min | Brief screen for diagnosis |
| OCD-specific measures | ||
| Yale-Brown Obsessive Compulsive Scale (YBOCS) | 30 min | Severity and OCD symptom types |
| Obsessive Compulsive Inventory-Revised (OCI-R) | 5 to 10 min | Self-report severity of OCD symptoms |
| Source: Data from references 10-14 | ||
The Yale-Brown Obsessive Compulsive Scale (YBOCS) is widely used.12,13 It includes a checklist of common obsessions and compulsions plus 10 items measuring interference with daily living, distress, resistance, control, and time spent on symptoms. Each item is scored from 0 to 4, for a total score of 0 to 40.
The YBOCS has good reliability and validity, is available in both clinician-rated and self-rated versions, and can be given repeatedly to measure treatment progress. A Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS) is useful for patients ages 6 to 17.16
TREATING UNCOMPLICATED OCD
CBT. When OCD is not concurrent with another diagnosis, expert consensus guidelines recommend CBT as first-line treatment.17 Most patients treated with exposure and response prevention (ERP) therapy—the specialized CBT for reducing anxiety that triggers obsessive-compulsive symptoms—report reduced symptoms and often maintain those gains over time.18
In specialty clinics, patients frequently engage in intensive ERP (2 hours per day, 3 to 5 times per week for about 3 weeks). Although studies find excellent outcomes with intensive OCD treatment,18 it is not always practical or indicated (as in patients with moderate symptoms). Less-intensive protocols, such as biweekly sessions, have also shown promise in studies examining how session frequency affects treatment outcome.19
Many studies supporting ERP’s efficacy in OCD have included relatively homogenous samples under well-controlled conditions. Some investigations have also found good effects for ERP when including patients with complex treatment histories, concomitant pharmacotherapy, and comorbid conditions.20
Medication. Functional imaging studies suggest that OCD results from dysregulation in the socalled “OCD circuit”—the orbitofrontal cortex, anterior cingulate, and caudate nucleus. In patients with OCD, metabolic activity in this region is increased at rest relative to controls, increases further with symptoms, and decreases after successful treatment.21 The serotonin hypothesis—which emerged from observation that OCD symptoms responded to serotonergic medications but not to noradrenergic ones—suggests serotonin system dysregulation in patients with OCD.
High dosages of SRIs—selective serotonin reuptake inhibitors or the tricyclic antidepressant clomipramine—are first-line OCD medications (Table 3). Double-blind clinical trials have found clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram more effective than placebo, and the first five of these drugs are FDA-approved for treating adult OCD.
Table 3
Serotonin reuptake inhibitors indicated for treating OCD*
| Drug | Starting dosage | Target dosage (adults) |
|---|---|---|
| Clomipramine | 25 mg/d | 150 to 200 mg/d |
| Fluoxetine | 20 mg/d | 60 to 80 mg/d |
| Fluvoxamine | 50 mg/d | 150 to 300 mg/d |
| Paroxetine | 20 mg/d | 40 to 60 mg/d |
| Sertraline | 50 mg/d | 150 to 200 mg/d |
| * 10- to 12-week medication trials at target doses; sequential trials may be required to achieve treatment response. | ||
Nonresponse. Patients typically require at least 10 to 12 weeks of treatment at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.22
The up to 40% of patients who do not respond to SRI therapy require alternate strategies:
- Augmenting SRI therapy with a low-dose atypical antipsychotic such as risperidone, 1 to 2 mg bid, or olanzapine, 5 to 10 mg/d, may be effective, even in patients without a comorbid psychotic or tic disorder.23,24 It is worth noting that trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.
- The serotonin-norepinephrine reuptake inhibitor venlafaxine, 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.25
- Augmentation with pindolol, lithium, buspirone, trazodone, tryptophan, or thyroid hormone has shown mixed results.24
FACTORING IN COMORBIDITIES
Acute risk? Conditions that endanger the patient take precedence over OCD treatment. Suicidal risk and self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting SRI therapy with an antipsychotic.17
Interfere with CBT? Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy. Thus, we recommend delaying OCD behavioral treatment until you treat or stabilize these conditions.
Many OCD patients report comorbid depression, which may be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depressionspecific interventions.
Patients with comorbid depression may not respond to OCD interventions as well as nondepressed OCD patients do.26 For concurrent OCD and major depression, expert consensus guidelines suggest combining CBT with an SRI.17
Less is known about how other comorbidities affect OCD treatment. In one study, patients with comorbid OCD and posttraumatic stress disorder (PTSD) responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.27 Some Axis II disorders—such as schizotypal, avoidant, paranoid, and borderline personality disorder—have also been found to predict poorer outcome in patients treated with clomipramine.3
Concurrent treatment? In some concomitant conditions, such as PTSD with OCD, preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.27 Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:
- constructing exposures for social anxiety disorder patients that, at least initially, minimize extraneous social contact and evaluative fears
- instructing panic disorder patients in anxiety management skills so that exposures do not trigger anxiety attacks and reinforce their fears.
Related resources
- Jenike MA, Baer L, Minichiello WE (eds). Obsessive-compulsive disorders: practical management (3rd ed). New York: Mosby, 1998.
- Clark DA. Cognitive-behavioral therapy for OCD. New York: Guilford Press, 2003.
- Obsessive-Compulsive Foundation. www.ocfoundation.org.
- Buspirone • BuSpar
- Citalopram • Celexa
- Clomipramine • Anafranil
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Olanzapine • Zyprexa
- Paroxetine • Paxil
- Risperidone • Risperdal
- Sertraline • Zoloft
- Trazodone • Desyrel
- Venlafaxine • Effexor
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Weissman MM, Bland RC, Canino GJ, et al. The cross national epidemiology of obsessive-compulsive disorder: The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl 3):5-10.
2. Overbeek T, Schruers K, Vermetten E, Griez E. Comborbidity of obsessive-compulsive disorder and depression: Prevalence, symptom severity, and treatment effect. J Clin Psychiatry 2002;63(12):1106-12.
3. Baer L, Jenike MA, Black DW, Treece C. Effects of Axis II diagnosis on treatment outcome with clomipramine in 55 patients with obsessive compulsive disorder. Arch Gen Psychiatry 1992;49(11):862-6.
4. Rasmussen SA, Eisen JL. The epidemiology and clinical features of obsessive compulsive disorder. Psychiatr Clin North Am 1992;15(4):743-58.
5. Rubenstein CS, Pigott TA, L’Heureux F, et al. A preliminary investigation of the lifetime prevalence of anorexia and bulimia nervosa in patients with obsessive compulsive disorder. J Clin Psychiatry 1992;53(9):309-14.
6. Perugi G, Akiskal HS, Pfanner C, et al. Clinical impact of bipolar and unipolar affective comorbidity on obsessive compulsive disorder. J Affect Disord 1997;46(1):15-23.
7. March J, Frances A, Kahn D, Carpenter D. Expert consensus guidelines: treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):1-72.
8. Foa EB, Liebowitz MR, Kozak MJ, et al. Randomized, placebo-controlled trial of exposure and response prevention, clomipramine, and their combination in the treatment of obsessive compulsive disorder. Am J Psychiatry 2005;162(1):151-61.
9. Kozak MJ, Liebowitz MR, Foa EB. Cognitive behavior therapy and pharmacotherapy for OCD: The NIMH-sponsored collaborative study. In: Goodman W, Rudorfer M, Maser J (eds). Obsessive compulsive disorder: Contemporary issues in treatment. Mahwah, NJ: Lawrence Erlbaum Associates, 2000;501:30.-
10. Brown TA, DiNardo PA, Barlow DH. Anxiety Disorders Interview Schedule for DSM-IV. New York: Graywind Publications, 1994.
11. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The MiniInternational Neuropsychiatric Interview (M.I.N.I): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):22-33.
12. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Arch Gen Psychiatry 1989;46(11):1006M-11.
13. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: II.Validity. Arch Gen Psychiatry 1989;46(11):1012-6.
14. Foa EB, Huppert JD, Leiberg S, et al. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 2002;14(4):485-96.
15. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition New York: New York State Psychiatric Institute, Biometrics Research Department, 1996.
16. Scahill L, Riddle M, McSwiggin-Hardin M, et al. Children’s Yale-Brown Obsessive-Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 1997;36(6):844-52.
17. Frances A, Docherty JP, Kahn DA. Treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):5-72.
18. Foa EB, Franklin ME. Psychotherapies for obsessive-compulsive disorder: A review. In: Maj M, Sartorius N, Okasha A, Zohar J (eds). Obsessive-Compulsive Disorder New York: Wiley, 2000;93:115.-
19. Abramowitz JS, Foa EB, Franklin ME. Exposure and ritual prevention for obsessive-compulsive disorder: Effect of intensive versus twice weekly sessions. J Consult Clin Psychol 2003;71(2):394-8.
20. Franklin ME, Abramowitz JS, Kozak MJ, et al. Effectiveness of exposure and ritual prevention for obsessive-compulsive disorder: Randomized compared with nonrandomized samples. J Consult Clin Psychol 2000;68(4):594-602.
21. Graybiel A, Rauch SL. Toward a neurobiology of obsessive compulsive disorder. Neuron 2000;28:343-7.
22. Pigott TA, Seay S. Pharmacology of obsessive compulsive disorder: overview and treatment-refractory strategies. In: Goodman MK, Rudorfer MV, Maser JD (eds). Obsessive compulsive disorder: contemporary issues in treatment Mahwah, NJ: Lawrence Erlbaum Associates, 2000;277:302.-
23. McDougle CJ, Epperson CN, Pelton GH, et al. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57(8):794-801.
24. Hollander E, Bienstock CA, Koran LM, et al. Refractory obsessive-compulsive disorder: state-of-the-art treatment. J Clin Psychiatry 2002;63(suppl 6):20-9.
25. Hollander E, Friedberg BS, Wasserman S, et al. Venlafaxine in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2003;64(5):546-50.
26. Abramowitz JS, Foa EB. Does major depressive disorder influence outcome of exposure and response prevention for OCD? Behavior Ther 2001;31(4):795-800.
27. Gershuny BS, Baer L, Jenike MA, et al. Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder. Am J Psychiatry 2002;159(5):852-4.
28. Perugi G, Toni C, Frare F, et al. Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical features and treatment outcome. J Clin Psychiatry 2002;63(12):1129-34.
Psychiatric comorbidities complicate the treatment of obsessive-compulsive disorder (OCD) and are much more the rule than the exception in clinical practice (Table 1).1-6 Even so, surprisingly few studies have examined comorbidities’ effects on OCD treatment, and results have been mixed.
For the typical patient with obsessive-compulsive symptoms, we discuss our experience and evidence that supports:
- clinically useful tools to differentiate OCD from other obsessive and anxiety disorders
- how to address comorbidities that pose acute danger or would prevent effective psychotherapy
- how to modify first-line OCD treatments—cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs)7-9—to also manage most comorbid disorders.
Table 1
Common psychiatric comorbidities with OCD
| Comorbidities | Estimated prevalence in OCD patients |
|---|---|
| Personality disorders | 63% |
| Major depressive disorder | 28 to 31% |
| Simple phobia | 7 to 48% |
| Social phobia | 11 to 16% |
| Bipolar disorder | 15% |
| Eating disorders | 8 to 13% |
| Alcohol abuse | 8% |
| Panic disorder | 6 to 12% |
| Tourette’s syndrome or tic disorders | 6 to 7% |
| Source: Data from references 1-6 | |
IS OCD PRIMARY?
OCD-like obsessive thoughts or repetitive behaviors may be evident in a number of psychiatric disorders. Distinguishing OCD from masquerading or co-occurring conditions is important because interventions can differ.
Patients with generalized anxiety disorder (GAD), for example, may experience ruminative, anxious thoughts that mimic obsessions. Somatoform conditions such as hypochondriasis or body dysmorphic disorder are characterized by intense preoccupation with illness or appearance, respectively. Repetitive or compulsive behaviors may be seen in impulse control or developmental disorders such as pathologic gambling, trichotillomania, and Asperger’s disorder.
To help differentiate OCD from these conditions, consider the function of a patient’s symptoms. In OCD, obsessions are experienced as ego-dystonic and generally cause great anxiety. OCD patients perform compulsive rituals to alleviate anxiety but do not gain pleasure from their actions. Contrast this with trichotillomania’s repetitive behavior—commonly experienced as pleasurable or gratifying—or with GAD’s ruminative thoughts—seen as ego-syntonic worries about real-life situations.
ASSESSING OCD, COMORBID CONDITIONS
When you suspect psychiatric comorbidity with OCD, an accurate and thorough assessment is key to successful treatment (Table 2).10-14
In specialty OCD clinics, the Structured Clinical Interview for DSM-IV (SCID-IV)15 or Anxiety Disorders Interview Schedule for the DSM-IV (ADIS-IV)10 are routinely given to assess the most common comorbid conditions. In clinical practice, however, these instruments can take up to several hours to perform, especially for patients who meet criteria for several disorders.
An alternative may be the Mini International Neuropsychiatric Interview (MINI).11 The MINI is a short, structured, diagnostic interview for DSM-IV and ICD-10 that takes about 15 minutes and screens for most conditions commonly comorbid with OCD. The MINI provides less-detailed information than the SCID-IV or the ADIS-IV but allows for a quick, accurate diagnosis while using a structured format.
Table 2
Common assessment tools for patients with suspected OCD
| Structured clinical interviews | Time to administer | Use |
|---|---|---|
| Anxiety Disorders Interview Schedule-IV (ADIS-IV) | 2+ hrs | Detailed assessment of anxiety disorders |
| Mini-International Neuropsychiatric Interview (MINI) | 15 to 30 min | Brief screen for diagnosis |
| OCD-specific measures | ||
| Yale-Brown Obsessive Compulsive Scale (YBOCS) | 30 min | Severity and OCD symptom types |
| Obsessive Compulsive Inventory-Revised (OCI-R) | 5 to 10 min | Self-report severity of OCD symptoms |
| Source: Data from references 10-14 | ||
The Yale-Brown Obsessive Compulsive Scale (YBOCS) is widely used.12,13 It includes a checklist of common obsessions and compulsions plus 10 items measuring interference with daily living, distress, resistance, control, and time spent on symptoms. Each item is scored from 0 to 4, for a total score of 0 to 40.
The YBOCS has good reliability and validity, is available in both clinician-rated and self-rated versions, and can be given repeatedly to measure treatment progress. A Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS) is useful for patients ages 6 to 17.16
TREATING UNCOMPLICATED OCD
CBT. When OCD is not concurrent with another diagnosis, expert consensus guidelines recommend CBT as first-line treatment.17 Most patients treated with exposure and response prevention (ERP) therapy—the specialized CBT for reducing anxiety that triggers obsessive-compulsive symptoms—report reduced symptoms and often maintain those gains over time.18
In specialty clinics, patients frequently engage in intensive ERP (2 hours per day, 3 to 5 times per week for about 3 weeks). Although studies find excellent outcomes with intensive OCD treatment,18 it is not always practical or indicated (as in patients with moderate symptoms). Less-intensive protocols, such as biweekly sessions, have also shown promise in studies examining how session frequency affects treatment outcome.19
Many studies supporting ERP’s efficacy in OCD have included relatively homogenous samples under well-controlled conditions. Some investigations have also found good effects for ERP when including patients with complex treatment histories, concomitant pharmacotherapy, and comorbid conditions.20
Medication. Functional imaging studies suggest that OCD results from dysregulation in the socalled “OCD circuit”—the orbitofrontal cortex, anterior cingulate, and caudate nucleus. In patients with OCD, metabolic activity in this region is increased at rest relative to controls, increases further with symptoms, and decreases after successful treatment.21 The serotonin hypothesis—which emerged from observation that OCD symptoms responded to serotonergic medications but not to noradrenergic ones—suggests serotonin system dysregulation in patients with OCD.
High dosages of SRIs—selective serotonin reuptake inhibitors or the tricyclic antidepressant clomipramine—are first-line OCD medications (Table 3). Double-blind clinical trials have found clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram more effective than placebo, and the first five of these drugs are FDA-approved for treating adult OCD.
Table 3
Serotonin reuptake inhibitors indicated for treating OCD*
| Drug | Starting dosage | Target dosage (adults) |
|---|---|---|
| Clomipramine | 25 mg/d | 150 to 200 mg/d |
| Fluoxetine | 20 mg/d | 60 to 80 mg/d |
| Fluvoxamine | 50 mg/d | 150 to 300 mg/d |
| Paroxetine | 20 mg/d | 40 to 60 mg/d |
| Sertraline | 50 mg/d | 150 to 200 mg/d |
| * 10- to 12-week medication trials at target doses; sequential trials may be required to achieve treatment response. | ||
Nonresponse. Patients typically require at least 10 to 12 weeks of treatment at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.22
The up to 40% of patients who do not respond to SRI therapy require alternate strategies:
- Augmenting SRI therapy with a low-dose atypical antipsychotic such as risperidone, 1 to 2 mg bid, or olanzapine, 5 to 10 mg/d, may be effective, even in patients without a comorbid psychotic or tic disorder.23,24 It is worth noting that trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.
- The serotonin-norepinephrine reuptake inhibitor venlafaxine, 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.25
- Augmentation with pindolol, lithium, buspirone, trazodone, tryptophan, or thyroid hormone has shown mixed results.24
FACTORING IN COMORBIDITIES
Acute risk? Conditions that endanger the patient take precedence over OCD treatment. Suicidal risk and self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting SRI therapy with an antipsychotic.17
Interfere with CBT? Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy. Thus, we recommend delaying OCD behavioral treatment until you treat or stabilize these conditions.
Many OCD patients report comorbid depression, which may be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depressionspecific interventions.
Patients with comorbid depression may not respond to OCD interventions as well as nondepressed OCD patients do.26 For concurrent OCD and major depression, expert consensus guidelines suggest combining CBT with an SRI.17
Less is known about how other comorbidities affect OCD treatment. In one study, patients with comorbid OCD and posttraumatic stress disorder (PTSD) responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.27 Some Axis II disorders—such as schizotypal, avoidant, paranoid, and borderline personality disorder—have also been found to predict poorer outcome in patients treated with clomipramine.3
Concurrent treatment? In some concomitant conditions, such as PTSD with OCD, preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.27 Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:
- constructing exposures for social anxiety disorder patients that, at least initially, minimize extraneous social contact and evaluative fears
- instructing panic disorder patients in anxiety management skills so that exposures do not trigger anxiety attacks and reinforce their fears.
Related resources
- Jenike MA, Baer L, Minichiello WE (eds). Obsessive-compulsive disorders: practical management (3rd ed). New York: Mosby, 1998.
- Clark DA. Cognitive-behavioral therapy for OCD. New York: Guilford Press, 2003.
- Obsessive-Compulsive Foundation. www.ocfoundation.org.
- Buspirone • BuSpar
- Citalopram • Celexa
- Clomipramine • Anafranil
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Olanzapine • Zyprexa
- Paroxetine • Paxil
- Risperidone • Risperdal
- Sertraline • Zoloft
- Trazodone • Desyrel
- Venlafaxine • Effexor
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Psychiatric comorbidities complicate the treatment of obsessive-compulsive disorder (OCD) and are much more the rule than the exception in clinical practice (Table 1).1-6 Even so, surprisingly few studies have examined comorbidities’ effects on OCD treatment, and results have been mixed.
For the typical patient with obsessive-compulsive symptoms, we discuss our experience and evidence that supports:
- clinically useful tools to differentiate OCD from other obsessive and anxiety disorders
- how to address comorbidities that pose acute danger or would prevent effective psychotherapy
- how to modify first-line OCD treatments—cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs)7-9—to also manage most comorbid disorders.
Table 1
Common psychiatric comorbidities with OCD
| Comorbidities | Estimated prevalence in OCD patients |
|---|---|
| Personality disorders | 63% |
| Major depressive disorder | 28 to 31% |
| Simple phobia | 7 to 48% |
| Social phobia | 11 to 16% |
| Bipolar disorder | 15% |
| Eating disorders | 8 to 13% |
| Alcohol abuse | 8% |
| Panic disorder | 6 to 12% |
| Tourette’s syndrome or tic disorders | 6 to 7% |
| Source: Data from references 1-6 | |
IS OCD PRIMARY?
OCD-like obsessive thoughts or repetitive behaviors may be evident in a number of psychiatric disorders. Distinguishing OCD from masquerading or co-occurring conditions is important because interventions can differ.
Patients with generalized anxiety disorder (GAD), for example, may experience ruminative, anxious thoughts that mimic obsessions. Somatoform conditions such as hypochondriasis or body dysmorphic disorder are characterized by intense preoccupation with illness or appearance, respectively. Repetitive or compulsive behaviors may be seen in impulse control or developmental disorders such as pathologic gambling, trichotillomania, and Asperger’s disorder.
To help differentiate OCD from these conditions, consider the function of a patient’s symptoms. In OCD, obsessions are experienced as ego-dystonic and generally cause great anxiety. OCD patients perform compulsive rituals to alleviate anxiety but do not gain pleasure from their actions. Contrast this with trichotillomania’s repetitive behavior—commonly experienced as pleasurable or gratifying—or with GAD’s ruminative thoughts—seen as ego-syntonic worries about real-life situations.
ASSESSING OCD, COMORBID CONDITIONS
When you suspect psychiatric comorbidity with OCD, an accurate and thorough assessment is key to successful treatment (Table 2).10-14
In specialty OCD clinics, the Structured Clinical Interview for DSM-IV (SCID-IV)15 or Anxiety Disorders Interview Schedule for the DSM-IV (ADIS-IV)10 are routinely given to assess the most common comorbid conditions. In clinical practice, however, these instruments can take up to several hours to perform, especially for patients who meet criteria for several disorders.
An alternative may be the Mini International Neuropsychiatric Interview (MINI).11 The MINI is a short, structured, diagnostic interview for DSM-IV and ICD-10 that takes about 15 minutes and screens for most conditions commonly comorbid with OCD. The MINI provides less-detailed information than the SCID-IV or the ADIS-IV but allows for a quick, accurate diagnosis while using a structured format.
Table 2
Common assessment tools for patients with suspected OCD
| Structured clinical interviews | Time to administer | Use |
|---|---|---|
| Anxiety Disorders Interview Schedule-IV (ADIS-IV) | 2+ hrs | Detailed assessment of anxiety disorders |
| Mini-International Neuropsychiatric Interview (MINI) | 15 to 30 min | Brief screen for diagnosis |
| OCD-specific measures | ||
| Yale-Brown Obsessive Compulsive Scale (YBOCS) | 30 min | Severity and OCD symptom types |
| Obsessive Compulsive Inventory-Revised (OCI-R) | 5 to 10 min | Self-report severity of OCD symptoms |
| Source: Data from references 10-14 | ||
The Yale-Brown Obsessive Compulsive Scale (YBOCS) is widely used.12,13 It includes a checklist of common obsessions and compulsions plus 10 items measuring interference with daily living, distress, resistance, control, and time spent on symptoms. Each item is scored from 0 to 4, for a total score of 0 to 40.
The YBOCS has good reliability and validity, is available in both clinician-rated and self-rated versions, and can be given repeatedly to measure treatment progress. A Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS) is useful for patients ages 6 to 17.16
TREATING UNCOMPLICATED OCD
CBT. When OCD is not concurrent with another diagnosis, expert consensus guidelines recommend CBT as first-line treatment.17 Most patients treated with exposure and response prevention (ERP) therapy—the specialized CBT for reducing anxiety that triggers obsessive-compulsive symptoms—report reduced symptoms and often maintain those gains over time.18
In specialty clinics, patients frequently engage in intensive ERP (2 hours per day, 3 to 5 times per week for about 3 weeks). Although studies find excellent outcomes with intensive OCD treatment,18 it is not always practical or indicated (as in patients with moderate symptoms). Less-intensive protocols, such as biweekly sessions, have also shown promise in studies examining how session frequency affects treatment outcome.19
Many studies supporting ERP’s efficacy in OCD have included relatively homogenous samples under well-controlled conditions. Some investigations have also found good effects for ERP when including patients with complex treatment histories, concomitant pharmacotherapy, and comorbid conditions.20
Medication. Functional imaging studies suggest that OCD results from dysregulation in the socalled “OCD circuit”—the orbitofrontal cortex, anterior cingulate, and caudate nucleus. In patients with OCD, metabolic activity in this region is increased at rest relative to controls, increases further with symptoms, and decreases after successful treatment.21 The serotonin hypothesis—which emerged from observation that OCD symptoms responded to serotonergic medications but not to noradrenergic ones—suggests serotonin system dysregulation in patients with OCD.
High dosages of SRIs—selective serotonin reuptake inhibitors or the tricyclic antidepressant clomipramine—are first-line OCD medications (Table 3). Double-blind clinical trials have found clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram more effective than placebo, and the first five of these drugs are FDA-approved for treating adult OCD.
Table 3
Serotonin reuptake inhibitors indicated for treating OCD*
| Drug | Starting dosage | Target dosage (adults) |
|---|---|---|
| Clomipramine | 25 mg/d | 150 to 200 mg/d |
| Fluoxetine | 20 mg/d | 60 to 80 mg/d |
| Fluvoxamine | 50 mg/d | 150 to 300 mg/d |
| Paroxetine | 20 mg/d | 40 to 60 mg/d |
| Sertraline | 50 mg/d | 150 to 200 mg/d |
| * 10- to 12-week medication trials at target doses; sequential trials may be required to achieve treatment response. | ||
Nonresponse. Patients typically require at least 10 to 12 weeks of treatment at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.22
The up to 40% of patients who do not respond to SRI therapy require alternate strategies:
- Augmenting SRI therapy with a low-dose atypical antipsychotic such as risperidone, 1 to 2 mg bid, or olanzapine, 5 to 10 mg/d, may be effective, even in patients without a comorbid psychotic or tic disorder.23,24 It is worth noting that trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.
- The serotonin-norepinephrine reuptake inhibitor venlafaxine, 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.25
- Augmentation with pindolol, lithium, buspirone, trazodone, tryptophan, or thyroid hormone has shown mixed results.24
FACTORING IN COMORBIDITIES
Acute risk? Conditions that endanger the patient take precedence over OCD treatment. Suicidal risk and self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting SRI therapy with an antipsychotic.17
Interfere with CBT? Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy. Thus, we recommend delaying OCD behavioral treatment until you treat or stabilize these conditions.
Many OCD patients report comorbid depression, which may be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depressionspecific interventions.
Patients with comorbid depression may not respond to OCD interventions as well as nondepressed OCD patients do.26 For concurrent OCD and major depression, expert consensus guidelines suggest combining CBT with an SRI.17
Less is known about how other comorbidities affect OCD treatment. In one study, patients with comorbid OCD and posttraumatic stress disorder (PTSD) responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.27 Some Axis II disorders—such as schizotypal, avoidant, paranoid, and borderline personality disorder—have also been found to predict poorer outcome in patients treated with clomipramine.3
Concurrent treatment? In some concomitant conditions, such as PTSD with OCD, preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.27 Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:
- constructing exposures for social anxiety disorder patients that, at least initially, minimize extraneous social contact and evaluative fears
- instructing panic disorder patients in anxiety management skills so that exposures do not trigger anxiety attacks and reinforce their fears.
Related resources
- Jenike MA, Baer L, Minichiello WE (eds). Obsessive-compulsive disorders: practical management (3rd ed). New York: Mosby, 1998.
- Clark DA. Cognitive-behavioral therapy for OCD. New York: Guilford Press, 2003.
- Obsessive-Compulsive Foundation. www.ocfoundation.org.
- Buspirone • BuSpar
- Citalopram • Celexa
- Clomipramine • Anafranil
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Olanzapine • Zyprexa
- Paroxetine • Paxil
- Risperidone • Risperdal
- Sertraline • Zoloft
- Trazodone • Desyrel
- Venlafaxine • Effexor
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Weissman MM, Bland RC, Canino GJ, et al. The cross national epidemiology of obsessive-compulsive disorder: The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl 3):5-10.
2. Overbeek T, Schruers K, Vermetten E, Griez E. Comborbidity of obsessive-compulsive disorder and depression: Prevalence, symptom severity, and treatment effect. J Clin Psychiatry 2002;63(12):1106-12.
3. Baer L, Jenike MA, Black DW, Treece C. Effects of Axis II diagnosis on treatment outcome with clomipramine in 55 patients with obsessive compulsive disorder. Arch Gen Psychiatry 1992;49(11):862-6.
4. Rasmussen SA, Eisen JL. The epidemiology and clinical features of obsessive compulsive disorder. Psychiatr Clin North Am 1992;15(4):743-58.
5. Rubenstein CS, Pigott TA, L’Heureux F, et al. A preliminary investigation of the lifetime prevalence of anorexia and bulimia nervosa in patients with obsessive compulsive disorder. J Clin Psychiatry 1992;53(9):309-14.
6. Perugi G, Akiskal HS, Pfanner C, et al. Clinical impact of bipolar and unipolar affective comorbidity on obsessive compulsive disorder. J Affect Disord 1997;46(1):15-23.
7. March J, Frances A, Kahn D, Carpenter D. Expert consensus guidelines: treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):1-72.
8. Foa EB, Liebowitz MR, Kozak MJ, et al. Randomized, placebo-controlled trial of exposure and response prevention, clomipramine, and their combination in the treatment of obsessive compulsive disorder. Am J Psychiatry 2005;162(1):151-61.
9. Kozak MJ, Liebowitz MR, Foa EB. Cognitive behavior therapy and pharmacotherapy for OCD: The NIMH-sponsored collaborative study. In: Goodman W, Rudorfer M, Maser J (eds). Obsessive compulsive disorder: Contemporary issues in treatment. Mahwah, NJ: Lawrence Erlbaum Associates, 2000;501:30.-
10. Brown TA, DiNardo PA, Barlow DH. Anxiety Disorders Interview Schedule for DSM-IV. New York: Graywind Publications, 1994.
11. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The MiniInternational Neuropsychiatric Interview (M.I.N.I): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):22-33.
12. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Arch Gen Psychiatry 1989;46(11):1006M-11.
13. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: II.Validity. Arch Gen Psychiatry 1989;46(11):1012-6.
14. Foa EB, Huppert JD, Leiberg S, et al. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 2002;14(4):485-96.
15. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition New York: New York State Psychiatric Institute, Biometrics Research Department, 1996.
16. Scahill L, Riddle M, McSwiggin-Hardin M, et al. Children’s Yale-Brown Obsessive-Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 1997;36(6):844-52.
17. Frances A, Docherty JP, Kahn DA. Treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):5-72.
18. Foa EB, Franklin ME. Psychotherapies for obsessive-compulsive disorder: A review. In: Maj M, Sartorius N, Okasha A, Zohar J (eds). Obsessive-Compulsive Disorder New York: Wiley, 2000;93:115.-
19. Abramowitz JS, Foa EB, Franklin ME. Exposure and ritual prevention for obsessive-compulsive disorder: Effect of intensive versus twice weekly sessions. J Consult Clin Psychol 2003;71(2):394-8.
20. Franklin ME, Abramowitz JS, Kozak MJ, et al. Effectiveness of exposure and ritual prevention for obsessive-compulsive disorder: Randomized compared with nonrandomized samples. J Consult Clin Psychol 2000;68(4):594-602.
21. Graybiel A, Rauch SL. Toward a neurobiology of obsessive compulsive disorder. Neuron 2000;28:343-7.
22. Pigott TA, Seay S. Pharmacology of obsessive compulsive disorder: overview and treatment-refractory strategies. In: Goodman MK, Rudorfer MV, Maser JD (eds). Obsessive compulsive disorder: contemporary issues in treatment Mahwah, NJ: Lawrence Erlbaum Associates, 2000;277:302.-
23. McDougle CJ, Epperson CN, Pelton GH, et al. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57(8):794-801.
24. Hollander E, Bienstock CA, Koran LM, et al. Refractory obsessive-compulsive disorder: state-of-the-art treatment. J Clin Psychiatry 2002;63(suppl 6):20-9.
25. Hollander E, Friedberg BS, Wasserman S, et al. Venlafaxine in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2003;64(5):546-50.
26. Abramowitz JS, Foa EB. Does major depressive disorder influence outcome of exposure and response prevention for OCD? Behavior Ther 2001;31(4):795-800.
27. Gershuny BS, Baer L, Jenike MA, et al. Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder. Am J Psychiatry 2002;159(5):852-4.
28. Perugi G, Toni C, Frare F, et al. Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical features and treatment outcome. J Clin Psychiatry 2002;63(12):1129-34.
1. Weissman MM, Bland RC, Canino GJ, et al. The cross national epidemiology of obsessive-compulsive disorder: The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl 3):5-10.
2. Overbeek T, Schruers K, Vermetten E, Griez E. Comborbidity of obsessive-compulsive disorder and depression: Prevalence, symptom severity, and treatment effect. J Clin Psychiatry 2002;63(12):1106-12.
3. Baer L, Jenike MA, Black DW, Treece C. Effects of Axis II diagnosis on treatment outcome with clomipramine in 55 patients with obsessive compulsive disorder. Arch Gen Psychiatry 1992;49(11):862-6.
4. Rasmussen SA, Eisen JL. The epidemiology and clinical features of obsessive compulsive disorder. Psychiatr Clin North Am 1992;15(4):743-58.
5. Rubenstein CS, Pigott TA, L’Heureux F, et al. A preliminary investigation of the lifetime prevalence of anorexia and bulimia nervosa in patients with obsessive compulsive disorder. J Clin Psychiatry 1992;53(9):309-14.
6. Perugi G, Akiskal HS, Pfanner C, et al. Clinical impact of bipolar and unipolar affective comorbidity on obsessive compulsive disorder. J Affect Disord 1997;46(1):15-23.
7. March J, Frances A, Kahn D, Carpenter D. Expert consensus guidelines: treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):1-72.
8. Foa EB, Liebowitz MR, Kozak MJ, et al. Randomized, placebo-controlled trial of exposure and response prevention, clomipramine, and their combination in the treatment of obsessive compulsive disorder. Am J Psychiatry 2005;162(1):151-61.
9. Kozak MJ, Liebowitz MR, Foa EB. Cognitive behavior therapy and pharmacotherapy for OCD: The NIMH-sponsored collaborative study. In: Goodman W, Rudorfer M, Maser J (eds). Obsessive compulsive disorder: Contemporary issues in treatment. Mahwah, NJ: Lawrence Erlbaum Associates, 2000;501:30.-
10. Brown TA, DiNardo PA, Barlow DH. Anxiety Disorders Interview Schedule for DSM-IV. New York: Graywind Publications, 1994.
11. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The MiniInternational Neuropsychiatric Interview (M.I.N.I): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):22-33.
12. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Arch Gen Psychiatry 1989;46(11):1006M-11.
13. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: II.Validity. Arch Gen Psychiatry 1989;46(11):1012-6.
14. Foa EB, Huppert JD, Leiberg S, et al. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 2002;14(4):485-96.
15. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition New York: New York State Psychiatric Institute, Biometrics Research Department, 1996.
16. Scahill L, Riddle M, McSwiggin-Hardin M, et al. Children’s Yale-Brown Obsessive-Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 1997;36(6):844-52.
17. Frances A, Docherty JP, Kahn DA. Treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):5-72.
18. Foa EB, Franklin ME. Psychotherapies for obsessive-compulsive disorder: A review. In: Maj M, Sartorius N, Okasha A, Zohar J (eds). Obsessive-Compulsive Disorder New York: Wiley, 2000;93:115.-
19. Abramowitz JS, Foa EB, Franklin ME. Exposure and ritual prevention for obsessive-compulsive disorder: Effect of intensive versus twice weekly sessions. J Consult Clin Psychol 2003;71(2):394-8.
20. Franklin ME, Abramowitz JS, Kozak MJ, et al. Effectiveness of exposure and ritual prevention for obsessive-compulsive disorder: Randomized compared with nonrandomized samples. J Consult Clin Psychol 2000;68(4):594-602.
21. Graybiel A, Rauch SL. Toward a neurobiology of obsessive compulsive disorder. Neuron 2000;28:343-7.
22. Pigott TA, Seay S. Pharmacology of obsessive compulsive disorder: overview and treatment-refractory strategies. In: Goodman MK, Rudorfer MV, Maser JD (eds). Obsessive compulsive disorder: contemporary issues in treatment Mahwah, NJ: Lawrence Erlbaum Associates, 2000;277:302.-
23. McDougle CJ, Epperson CN, Pelton GH, et al. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57(8):794-801.
24. Hollander E, Bienstock CA, Koran LM, et al. Refractory obsessive-compulsive disorder: state-of-the-art treatment. J Clin Psychiatry 2002;63(suppl 6):20-9.
25. Hollander E, Friedberg BS, Wasserman S, et al. Venlafaxine in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2003;64(5):546-50.
26. Abramowitz JS, Foa EB. Does major depressive disorder influence outcome of exposure and response prevention for OCD? Behavior Ther 2001;31(4):795-800.
27. Gershuny BS, Baer L, Jenike MA, et al. Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder. Am J Psychiatry 2002;159(5):852-4.
28. Perugi G, Toni C, Frare F, et al. Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical features and treatment outcome. J Clin Psychiatry 2002;63(12):1129-34.
Balanced therapy: How to avoid conflict, help ‘borderline’ patients
Treating borderline personality disorder can seem like a no-win situation. If we try traditional cognitive-behavioral therapy (CBT) and emphasize change, patients feel unheard and invalidated; they may withdraw, quit, or even attack. But if we suggest ways to accept unhappy situations, they may feel we don’t understand their suffering.
A more effective approach is dialectical behavior therapy (DBT), first developed to treat highly suicidal persons with borderline personality disorder and used with other populations that have difficulty regulating their emotions.
This article describes how invalidating environments may damage emotional health and suggests how psychiatrists can use DBT’s methods when treating borderline personality disorder.
BIOLOGY PLUS ENVIRONMENT
For the patient, borderline personality disorder’s behavior clusters (Table 1):
- function to regulate emotions
- or result from emotion dysregulation.
DBT theory identifies emotion dysregulation as the primary deficit in borderline personality disorder. Biologically based emotional vulnerability is seen as interacting with an inability to modulate emotions because of a skills deficit.
Emotional vulnerability. Three characteristics—high sensitivity, high reactivity, and slow return to baseline emotional state—define high emotional vulnerability:
High sensitivity. The person reacts more quickly and to more things than do others in emotion-provoking situations. When walking, for example, they may pass someone who doesn’t say hello. Most people would shrug this off, but persons with high emotional sensitivity may quickly notice, assume there is a problem, feel they have done something wrong, then feel shame and anger.
High reactivity. Their emotional reactions are large, and the high arousal dysregulates cognitive processing.
Slow return to baseline. Events stack up because emotional reactions are long-lasting for persons with high emotional vulnerability. They don’t have time to get over one thing before something else happens.
DBT postulates that, over time, borderline personality disorder results from the transaction of biological emotional vulnerability and an invalidating environment. This therapeutic model asserts that biology and the environment are flexible, and interventions may influence both.
Invalidating environment. DBT acknowledges that invalidation occurs in all environments, even nuturing ones. It becomes detrimental when a vulnerable person is exposed to pervasive invalidation that is not related to the validity of the person’s behavior or to the person’s expressed emotions or thoughts.
An invalidating environment has three characteristic patterns. One is indiscriminate rejection of communication of private experiences and self-generated behaviors.
Case examples. Mary, age 8, says she’s been teased and it hurt her feelings. Her mother tells her she is making too much of the incident. Mary questions herself and searches the social environment for cues about how to respond to similar situations in the future.
Robbie, age 4, completes a drawing and shows it to his father with delight. His father points out some “sloppy” coloring. If his father repeatedly finds fault with his work, Robbie is likely to not show him his work or stop drawing, and his expressions of delight are likely to decrease.
Invalidating environments may also punish emotional displays and intermittently reinforce emotional escalation. Someone may show disapproval for or ignore a person’s genuine sadness or fear but attend to angry outbursts that result when the person feels ignored.
The third invalidating pattern is to oversimplify the ease of problem-solving and meeting goals.
Case example. As a child, when Susan asked for help, her mother would say “just do it,” without considering the skills her daughter needed to accomplish tasks. When Susan became frustrated, her mother demanded that she “just stop cying,” even though no person could modulate his or her emotions that quickly. As an adult, Susan now sets unrealistic goals and expectations for herself and despairs when she is unable to solve problems in her life.
These three invalidating patterns cause persons to search the social environment for cues about how to respond to situations. They may question themselves, their identity, and the appropriateness of any emotional expression. As a result, they may oscillate between emotional inhibition and extreme emotional styles, set unrealistic goals and expectations for themselves, and eventually despair of being able to solve their problems.
Specific to borderline personality disorder is that the environment ignores genuine emotional expression, and the individual’s emotions escalate. This pattern is reinforced when the listener finally rewards emotionally extreme behavior with attention or desired changes.
As the pattern is repeated over time, extreme emotional reactions become the norm rather than the exception, and the emotional chaos can make the person wish to die. Acting on that desire when past expressions of desperation have been ignored or invalidated can provide attention or interventions that would never happen after simple emotional expressions.
Thus, an environment that does not recognize or validate genuine emotional expression can reinforce suicidality.
Table 1
Diagnostic criteria for borderline personality disorder
A pervasive pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the following:
|
| Source: Adapted and reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders (4th ed, text revision). Copyright 2000. American Psychiatric Association. |
SOLVING NO-WIN THERAPY
Pitfalls with emphasizing change. Therapy that emphasizes solving problems and getting things to change typically triggers high arousal in persons with borderline personality disorder. Feeling out of control, they respond by trying to get in control, including attempts to control the therapist.
Similarly, they see attempts to get them to change their behavior as invalidating their experiences or, worse, who they are. Intense emotions aroused by the message they hear—that they are the source of their problems—impair learning and intensify their efforts to gain control. In a battle for control, collaboration and therapy cannot occur.
Case example. Ms. K wants you to understand how difficult her life is because of difficulties with her boss. You start talking about what Ms. K can do to change the situation, without acknowledging how difficult it is to deal with her boss.
Ms. K feels upset and says you don’t understand. For her, the interaction has led to emotion dysregulation and impaired cognitive processing.
Pitfalls with emphasizing acceptance. Most persons who come to therapy very distressed want something in their lives to change. If your primary message is acceptance instead of change, they may lose confidence in you.
Case example. Ms. K wants help dealing with her boss, who is making life quite difficult. As her therapist, you respond with warmth and acceptance but offer no suggestions as to how she might change the situation. Ms. K likes the way you listen to her but abandons therapy. after several sessions.
At first, patients with borderline personality disorder may like the warmth of client-centered acceptance approaches. Over time, however, they may feel their therapy sessions are out of control. They may think the therapist doesn’t understand the situation, doesn’t know how to help, or that situations that are troubling them cannot be changed.
Balanced therapy. DBT solves the change-or-acceptance dilemma by attempting to help patients with borderline personality disorder change themselves and their lives while offering strategies for accepting themselves and their situations.1,2 DBT includes problem-solving and acceptance strategies (Table 2).
Table 2
Strategies used in dialectical behavioral therapy
| Structural strategies | Organization of sessions, attending to the treatment hierarchy, reviewing progress, checking on other modes of therapy |
| Problem assessment strategies | Defining problems with specificity, conducting chain analyses, developing and testing hypotheses |
| Problem solving strategies | Providing didactic information, generating and evaluating solutions, teaching skills and coaching on use of skills, generalizing skills to the real-world environment |
| Contingency management | Use of reinforcement, extinction, aversive contingencies, and principles of shaping. |
| Exposure-based procedures | Both formal and informal |
| Cognitive strategies | Contingency clarification, observation and description of cognitions, cognitive modification |
| Validation strategies | Appearing interested, accurately reflecting, correctly articulating things that have not been fully expressed, explaining behavior in terms of learning history or biological factors, acknowledging validity of responses in terms of current events, interacting in a radically genuine manner, communicating belief in the patient |
| Reciprocal communication strategies | Being responsive, expressing warm engagement, being nonjudgmental, using self-disclosure, maintaining a reasonable power equilibrium |
| Irreverent strategies | Engaging in a matter-of-fact manner, directly confronting dysfunctional behavior, using unexpected, irreverent or humorous responses |
| Dialectical strategies | Using a balanced style, balancing acceptance-oriented strategies with change-oriented strategies, magnifying tension, using metaphor, modeling dialectical thinking and behaviors, moving with speed and flow. |
| Case management strategies | Following a model of consultation to the patient when long-term outcome is more important than short-term outcome; intervening in the patient's environment when short-term outcome is more important than long-term outcome |
DBT’S 4 THERAPY STAGES
DBT is a comprehensive treatment. The original outpatient model for borderline personality disorder (Table 3) has been adapted to different settings and applied to other populations.
Outpatients meet weekly in individual psychotherapy and a skills training group.3 Therapists also meet weekly in a consultation team viewed as “therapy for the therapist.”
Between sessions, therapists consult with patients by telephone to:
- decrease suicide crisis behaviors
- increase generalization of behavioral skills
- decrease patients’ feelings of conflict, alienation, or distance with the therapist.
Four stages. DBT follows four stages. For persons with borderline personality disorder, researchers have evaluated the efficacy of stage-1 therapy. Studies on stage-3 DBT have been conducted with nonborderline-personality individuals with eating disorders. The goals at each stage are:
Stage 1. Move from severe behavioral dyscontrol to behavioral control. Decrease suicidal and other life-threatening behaviors and those that interfere with therapy and quality of life. Increase mindfulness, tolerance for distress, interpersonal effectiveness, and emotion regulation.
Stage 2. Move from quiet desperation to emotional experiencing.
Stage 3. Address problems in living, and move toward ordinary happiness/unhappiness.
Stage 4. Move from incompleteness to capacity for joy and freedom.
Seven randomized controlled trials have shown that DBT can be useful in treating borderline personality disorder.4-10 The initial trial by Linehan et al4 included 47 women ages 18 to 45 who met criteria for borderline personality disorder and had at least two parasuicide incidents in the previous 5 years, with one in the previous 8 weeks. Treatment lasted 1 year, and subjects agreed to stop other individual psychotherapy if assigned to DBT.
Subjects were then randomly assigned to either DBT or “treatment as usual” in the community. In the various DBT studies, treatment-as-usual has included community therapists, Department of Veterans Affairs outpatient treatment, client-centered therapy, and treatment by persons identified by their peers as experts in their communities.
Subjects were assessed every 4 months while in treatment and for 1 year thereafter. DBT was more effective than usual treatment in:
- reducing suicide attempts and self-injury
- decreasing premature dropout from therapy
- reducing emergency room admissions and length of psychiatric hospitalization
- reducing drug abuse, depression, hopelessness, and anger.
Table 3
Modes of therapy in outpatient dialectical behavioral therapy
| Therapeutic goals | Mode |
|---|---|
| Improve motivational factors | Individual psychotherapy |
| Enhance capabilities | Skills training |
| Ensure generalization to natural environment | Between-session consultation |
| Enhance therapist capabilities and motivation to treat effectively | Therapist consultation team |
| Structure the environment | Consultation to the patient |
RECOMMENDATIONS
Some psychiatrists may find “borderline patients” frustrating and unpleasant to treat. DBT therapists, however, make two assumptions that can help anyone working with individuals with borderline personality disorder. To avoid falling into the trap of polarization with these patients, assume that:
- they are doing the best they can
- their efforts are insufficient to meet their needs.
They therefore need to do better, and the therapist’s job is to help them do so. Also assume that if you try to help a patient with borderline personality disorder, you will need help, too. We require DBT therapists to participate in consultation teams.
Training. DBT is a comprehensive program that requires familiarity with the manuals mentioned in this article (see Related resources). Some teams have learned DBT through self-study and consultation with other teams.
If you plan to offer DBT to patients with borderline personality disorder, we recommend that you be:
- trained in behavior therapy and CBT
- familiar with research on emotions and processes involved in emotion regulation.
If you have not had CBT training, find a behavior therapist to join your team or get consultation from a behavior therapist.
An intensive training course in DBT—with 2 weeks of instruction and case consultation and several months of consultation with someone well-versed in DBT—is an efficient way to become familiar with the most critical principles of the treatment. If you cannot train toward adherent delivery of individual therapy, we recommend referring patients to someone trained in DBT.
- Lieb K, Zanarini MC, Schmahl C, et al. Borderline personality disorder. Lancet 2004;364(9432):453-61.
- University of Washington, Behavioral Research and Therapy Clinics. www.brtc.psych.washington.edu/frameResearch.htm;
www.brtc.psych.washington.edu/framePublications.htm - Behavioral Tech, LLC. Consultation and training in dialectical behavioral therapy. www.behavioraltech.org.
Disclosures
Dr. DuBose is president and CEO/co-owner of DBT Center of Seattle, PLLC, and a speaker for Behavioral Tech, LLC.
Dr. Linehan is a shareholder in Behavioral Tech Research, Inc., which develops computerized training for DBT, a DBT trainer for Behavioral Tech, LLC, and the author of two books on DBT. She also receives research grants from the National Institute of Mental Health and National Institute on Drug Abuse.
1. Lynch TR, Chapman AL, Rosenthal MZ, et al. Mechanisms of change in dialectical behavior therapy: theoretical and empirical observations. J Clin Psychol 2005 (in press).
2. Linehan MM. Cognitive-behavioral treatment of borderline personality disorder. New York: Guilford Press, 1993.
3. Linehan MM. Skills training manual for treating borderline personality disorder. New York: Guilford Press, 1993.
4. Linehan MM, Armstrong HE, Suarez A, et al. Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Arch Gen Psychiatry 1991 Dec;48(12):1060-4.
5. Linehan MM, Schmidt HI, Dimeff LA, et al. Dialectical behavior therapy for patients with border-line personality disorder and drug-dependence. Am J Addict 1999;8:279-92.
6. Linehan MM, Dimeff LA, Reynolds SK, et al. Dialectical behavior therapy versus comprehensive validation therapy plus 12-step for the treatment of opioid dependent women meeting criteria for borderline personality disorder. Drug Alcohol Depend 2002;67(1):13-26.
7. Turner RM. Naturalistic evaluation of dialectical behavior therapy-oriented treatment for borderline personality disorders. Cognit Behav Pract 2000;7:413-19.
8. Koons CR, Robins CJ, Tweed JL, et al. Efficacy of dialectical behavior therapy in women veterans with borderline personality disorder. Behav Ther 2001;32:371-90.
9. Verheul R, Van Den Bosch LM, Koeter MW, et al. Dialectical behaviour therapy for women with borderline personality disorder: 12-month, randomised clinical trial in The Netherlands. Br J Psychiatry 2003;182:135-40.
10. Linehan MM, Comtois KA, Brown M, et al. DBT versus nonbehavioral treatment by experts in the community: clinical outcomes. Symposium presentation for the Association for Advancement of Behavior Therapy. University of Washington, Reno NV, 2002.
Treating borderline personality disorder can seem like a no-win situation. If we try traditional cognitive-behavioral therapy (CBT) and emphasize change, patients feel unheard and invalidated; they may withdraw, quit, or even attack. But if we suggest ways to accept unhappy situations, they may feel we don’t understand their suffering.
A more effective approach is dialectical behavior therapy (DBT), first developed to treat highly suicidal persons with borderline personality disorder and used with other populations that have difficulty regulating their emotions.
This article describes how invalidating environments may damage emotional health and suggests how psychiatrists can use DBT’s methods when treating borderline personality disorder.
BIOLOGY PLUS ENVIRONMENT
For the patient, borderline personality disorder’s behavior clusters (Table 1):
- function to regulate emotions
- or result from emotion dysregulation.
DBT theory identifies emotion dysregulation as the primary deficit in borderline personality disorder. Biologically based emotional vulnerability is seen as interacting with an inability to modulate emotions because of a skills deficit.
Emotional vulnerability. Three characteristics—high sensitivity, high reactivity, and slow return to baseline emotional state—define high emotional vulnerability:
High sensitivity. The person reacts more quickly and to more things than do others in emotion-provoking situations. When walking, for example, they may pass someone who doesn’t say hello. Most people would shrug this off, but persons with high emotional sensitivity may quickly notice, assume there is a problem, feel they have done something wrong, then feel shame and anger.
High reactivity. Their emotional reactions are large, and the high arousal dysregulates cognitive processing.
Slow return to baseline. Events stack up because emotional reactions are long-lasting for persons with high emotional vulnerability. They don’t have time to get over one thing before something else happens.
DBT postulates that, over time, borderline personality disorder results from the transaction of biological emotional vulnerability and an invalidating environment. This therapeutic model asserts that biology and the environment are flexible, and interventions may influence both.
Invalidating environment. DBT acknowledges that invalidation occurs in all environments, even nuturing ones. It becomes detrimental when a vulnerable person is exposed to pervasive invalidation that is not related to the validity of the person’s behavior or to the person’s expressed emotions or thoughts.
An invalidating environment has three characteristic patterns. One is indiscriminate rejection of communication of private experiences and self-generated behaviors.
Case examples. Mary, age 8, says she’s been teased and it hurt her feelings. Her mother tells her she is making too much of the incident. Mary questions herself and searches the social environment for cues about how to respond to similar situations in the future.
Robbie, age 4, completes a drawing and shows it to his father with delight. His father points out some “sloppy” coloring. If his father repeatedly finds fault with his work, Robbie is likely to not show him his work or stop drawing, and his expressions of delight are likely to decrease.
Invalidating environments may also punish emotional displays and intermittently reinforce emotional escalation. Someone may show disapproval for or ignore a person’s genuine sadness or fear but attend to angry outbursts that result when the person feels ignored.
The third invalidating pattern is to oversimplify the ease of problem-solving and meeting goals.
Case example. As a child, when Susan asked for help, her mother would say “just do it,” without considering the skills her daughter needed to accomplish tasks. When Susan became frustrated, her mother demanded that she “just stop cying,” even though no person could modulate his or her emotions that quickly. As an adult, Susan now sets unrealistic goals and expectations for herself and despairs when she is unable to solve problems in her life.
These three invalidating patterns cause persons to search the social environment for cues about how to respond to situations. They may question themselves, their identity, and the appropriateness of any emotional expression. As a result, they may oscillate between emotional inhibition and extreme emotional styles, set unrealistic goals and expectations for themselves, and eventually despair of being able to solve their problems.
Specific to borderline personality disorder is that the environment ignores genuine emotional expression, and the individual’s emotions escalate. This pattern is reinforced when the listener finally rewards emotionally extreme behavior with attention or desired changes.
As the pattern is repeated over time, extreme emotional reactions become the norm rather than the exception, and the emotional chaos can make the person wish to die. Acting on that desire when past expressions of desperation have been ignored or invalidated can provide attention or interventions that would never happen after simple emotional expressions.
Thus, an environment that does not recognize or validate genuine emotional expression can reinforce suicidality.
Table 1
Diagnostic criteria for borderline personality disorder
A pervasive pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the following:
|
| Source: Adapted and reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders (4th ed, text revision). Copyright 2000. American Psychiatric Association. |
SOLVING NO-WIN THERAPY
Pitfalls with emphasizing change. Therapy that emphasizes solving problems and getting things to change typically triggers high arousal in persons with borderline personality disorder. Feeling out of control, they respond by trying to get in control, including attempts to control the therapist.
Similarly, they see attempts to get them to change their behavior as invalidating their experiences or, worse, who they are. Intense emotions aroused by the message they hear—that they are the source of their problems—impair learning and intensify their efforts to gain control. In a battle for control, collaboration and therapy cannot occur.
Case example. Ms. K wants you to understand how difficult her life is because of difficulties with her boss. You start talking about what Ms. K can do to change the situation, without acknowledging how difficult it is to deal with her boss.
Ms. K feels upset and says you don’t understand. For her, the interaction has led to emotion dysregulation and impaired cognitive processing.
Pitfalls with emphasizing acceptance. Most persons who come to therapy very distressed want something in their lives to change. If your primary message is acceptance instead of change, they may lose confidence in you.
Case example. Ms. K wants help dealing with her boss, who is making life quite difficult. As her therapist, you respond with warmth and acceptance but offer no suggestions as to how she might change the situation. Ms. K likes the way you listen to her but abandons therapy. after several sessions.
At first, patients with borderline personality disorder may like the warmth of client-centered acceptance approaches. Over time, however, they may feel their therapy sessions are out of control. They may think the therapist doesn’t understand the situation, doesn’t know how to help, or that situations that are troubling them cannot be changed.
Balanced therapy. DBT solves the change-or-acceptance dilemma by attempting to help patients with borderline personality disorder change themselves and their lives while offering strategies for accepting themselves and their situations.1,2 DBT includes problem-solving and acceptance strategies (Table 2).
Table 2
Strategies used in dialectical behavioral therapy
| Structural strategies | Organization of sessions, attending to the treatment hierarchy, reviewing progress, checking on other modes of therapy |
| Problem assessment strategies | Defining problems with specificity, conducting chain analyses, developing and testing hypotheses |
| Problem solving strategies | Providing didactic information, generating and evaluating solutions, teaching skills and coaching on use of skills, generalizing skills to the real-world environment |
| Contingency management | Use of reinforcement, extinction, aversive contingencies, and principles of shaping. |
| Exposure-based procedures | Both formal and informal |
| Cognitive strategies | Contingency clarification, observation and description of cognitions, cognitive modification |
| Validation strategies | Appearing interested, accurately reflecting, correctly articulating things that have not been fully expressed, explaining behavior in terms of learning history or biological factors, acknowledging validity of responses in terms of current events, interacting in a radically genuine manner, communicating belief in the patient |
| Reciprocal communication strategies | Being responsive, expressing warm engagement, being nonjudgmental, using self-disclosure, maintaining a reasonable power equilibrium |
| Irreverent strategies | Engaging in a matter-of-fact manner, directly confronting dysfunctional behavior, using unexpected, irreverent or humorous responses |
| Dialectical strategies | Using a balanced style, balancing acceptance-oriented strategies with change-oriented strategies, magnifying tension, using metaphor, modeling dialectical thinking and behaviors, moving with speed and flow. |
| Case management strategies | Following a model of consultation to the patient when long-term outcome is more important than short-term outcome; intervening in the patient's environment when short-term outcome is more important than long-term outcome |
DBT’S 4 THERAPY STAGES
DBT is a comprehensive treatment. The original outpatient model for borderline personality disorder (Table 3) has been adapted to different settings and applied to other populations.
Outpatients meet weekly in individual psychotherapy and a skills training group.3 Therapists also meet weekly in a consultation team viewed as “therapy for the therapist.”
Between sessions, therapists consult with patients by telephone to:
- decrease suicide crisis behaviors
- increase generalization of behavioral skills
- decrease patients’ feelings of conflict, alienation, or distance with the therapist.
Four stages. DBT follows four stages. For persons with borderline personality disorder, researchers have evaluated the efficacy of stage-1 therapy. Studies on stage-3 DBT have been conducted with nonborderline-personality individuals with eating disorders. The goals at each stage are:
Stage 1. Move from severe behavioral dyscontrol to behavioral control. Decrease suicidal and other life-threatening behaviors and those that interfere with therapy and quality of life. Increase mindfulness, tolerance for distress, interpersonal effectiveness, and emotion regulation.
Stage 2. Move from quiet desperation to emotional experiencing.
Stage 3. Address problems in living, and move toward ordinary happiness/unhappiness.
Stage 4. Move from incompleteness to capacity for joy and freedom.
Seven randomized controlled trials have shown that DBT can be useful in treating borderline personality disorder.4-10 The initial trial by Linehan et al4 included 47 women ages 18 to 45 who met criteria for borderline personality disorder and had at least two parasuicide incidents in the previous 5 years, with one in the previous 8 weeks. Treatment lasted 1 year, and subjects agreed to stop other individual psychotherapy if assigned to DBT.
Subjects were then randomly assigned to either DBT or “treatment as usual” in the community. In the various DBT studies, treatment-as-usual has included community therapists, Department of Veterans Affairs outpatient treatment, client-centered therapy, and treatment by persons identified by their peers as experts in their communities.
Subjects were assessed every 4 months while in treatment and for 1 year thereafter. DBT was more effective than usual treatment in:
- reducing suicide attempts and self-injury
- decreasing premature dropout from therapy
- reducing emergency room admissions and length of psychiatric hospitalization
- reducing drug abuse, depression, hopelessness, and anger.
Table 3
Modes of therapy in outpatient dialectical behavioral therapy
| Therapeutic goals | Mode |
|---|---|
| Improve motivational factors | Individual psychotherapy |
| Enhance capabilities | Skills training |
| Ensure generalization to natural environment | Between-session consultation |
| Enhance therapist capabilities and motivation to treat effectively | Therapist consultation team |
| Structure the environment | Consultation to the patient |
RECOMMENDATIONS
Some psychiatrists may find “borderline patients” frustrating and unpleasant to treat. DBT therapists, however, make two assumptions that can help anyone working with individuals with borderline personality disorder. To avoid falling into the trap of polarization with these patients, assume that:
- they are doing the best they can
- their efforts are insufficient to meet their needs.
They therefore need to do better, and the therapist’s job is to help them do so. Also assume that if you try to help a patient with borderline personality disorder, you will need help, too. We require DBT therapists to participate in consultation teams.
Training. DBT is a comprehensive program that requires familiarity with the manuals mentioned in this article (see Related resources). Some teams have learned DBT through self-study and consultation with other teams.
If you plan to offer DBT to patients with borderline personality disorder, we recommend that you be:
- trained in behavior therapy and CBT
- familiar with research on emotions and processes involved in emotion regulation.
If you have not had CBT training, find a behavior therapist to join your team or get consultation from a behavior therapist.
An intensive training course in DBT—with 2 weeks of instruction and case consultation and several months of consultation with someone well-versed in DBT—is an efficient way to become familiar with the most critical principles of the treatment. If you cannot train toward adherent delivery of individual therapy, we recommend referring patients to someone trained in DBT.
- Lieb K, Zanarini MC, Schmahl C, et al. Borderline personality disorder. Lancet 2004;364(9432):453-61.
- University of Washington, Behavioral Research and Therapy Clinics. www.brtc.psych.washington.edu/frameResearch.htm;
www.brtc.psych.washington.edu/framePublications.htm - Behavioral Tech, LLC. Consultation and training in dialectical behavioral therapy. www.behavioraltech.org.
Disclosures
Dr. DuBose is president and CEO/co-owner of DBT Center of Seattle, PLLC, and a speaker for Behavioral Tech, LLC.
Dr. Linehan is a shareholder in Behavioral Tech Research, Inc., which develops computerized training for DBT, a DBT trainer for Behavioral Tech, LLC, and the author of two books on DBT. She also receives research grants from the National Institute of Mental Health and National Institute on Drug Abuse.
Treating borderline personality disorder can seem like a no-win situation. If we try traditional cognitive-behavioral therapy (CBT) and emphasize change, patients feel unheard and invalidated; they may withdraw, quit, or even attack. But if we suggest ways to accept unhappy situations, they may feel we don’t understand their suffering.
A more effective approach is dialectical behavior therapy (DBT), first developed to treat highly suicidal persons with borderline personality disorder and used with other populations that have difficulty regulating their emotions.
This article describes how invalidating environments may damage emotional health and suggests how psychiatrists can use DBT’s methods when treating borderline personality disorder.
BIOLOGY PLUS ENVIRONMENT
For the patient, borderline personality disorder’s behavior clusters (Table 1):
- function to regulate emotions
- or result from emotion dysregulation.
DBT theory identifies emotion dysregulation as the primary deficit in borderline personality disorder. Biologically based emotional vulnerability is seen as interacting with an inability to modulate emotions because of a skills deficit.
Emotional vulnerability. Three characteristics—high sensitivity, high reactivity, and slow return to baseline emotional state—define high emotional vulnerability:
High sensitivity. The person reacts more quickly and to more things than do others in emotion-provoking situations. When walking, for example, they may pass someone who doesn’t say hello. Most people would shrug this off, but persons with high emotional sensitivity may quickly notice, assume there is a problem, feel they have done something wrong, then feel shame and anger.
High reactivity. Their emotional reactions are large, and the high arousal dysregulates cognitive processing.
Slow return to baseline. Events stack up because emotional reactions are long-lasting for persons with high emotional vulnerability. They don’t have time to get over one thing before something else happens.
DBT postulates that, over time, borderline personality disorder results from the transaction of biological emotional vulnerability and an invalidating environment. This therapeutic model asserts that biology and the environment are flexible, and interventions may influence both.
Invalidating environment. DBT acknowledges that invalidation occurs in all environments, even nuturing ones. It becomes detrimental when a vulnerable person is exposed to pervasive invalidation that is not related to the validity of the person’s behavior or to the person’s expressed emotions or thoughts.
An invalidating environment has three characteristic patterns. One is indiscriminate rejection of communication of private experiences and self-generated behaviors.
Case examples. Mary, age 8, says she’s been teased and it hurt her feelings. Her mother tells her she is making too much of the incident. Mary questions herself and searches the social environment for cues about how to respond to similar situations in the future.
Robbie, age 4, completes a drawing and shows it to his father with delight. His father points out some “sloppy” coloring. If his father repeatedly finds fault with his work, Robbie is likely to not show him his work or stop drawing, and his expressions of delight are likely to decrease.
Invalidating environments may also punish emotional displays and intermittently reinforce emotional escalation. Someone may show disapproval for or ignore a person’s genuine sadness or fear but attend to angry outbursts that result when the person feels ignored.
The third invalidating pattern is to oversimplify the ease of problem-solving and meeting goals.
Case example. As a child, when Susan asked for help, her mother would say “just do it,” without considering the skills her daughter needed to accomplish tasks. When Susan became frustrated, her mother demanded that she “just stop cying,” even though no person could modulate his or her emotions that quickly. As an adult, Susan now sets unrealistic goals and expectations for herself and despairs when she is unable to solve problems in her life.
These three invalidating patterns cause persons to search the social environment for cues about how to respond to situations. They may question themselves, their identity, and the appropriateness of any emotional expression. As a result, they may oscillate between emotional inhibition and extreme emotional styles, set unrealistic goals and expectations for themselves, and eventually despair of being able to solve their problems.
Specific to borderline personality disorder is that the environment ignores genuine emotional expression, and the individual’s emotions escalate. This pattern is reinforced when the listener finally rewards emotionally extreme behavior with attention or desired changes.
As the pattern is repeated over time, extreme emotional reactions become the norm rather than the exception, and the emotional chaos can make the person wish to die. Acting on that desire when past expressions of desperation have been ignored or invalidated can provide attention or interventions that would never happen after simple emotional expressions.
Thus, an environment that does not recognize or validate genuine emotional expression can reinforce suicidality.
Table 1
Diagnostic criteria for borderline personality disorder
A pervasive pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the following:
|
| Source: Adapted and reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders (4th ed, text revision). Copyright 2000. American Psychiatric Association. |
SOLVING NO-WIN THERAPY
Pitfalls with emphasizing change. Therapy that emphasizes solving problems and getting things to change typically triggers high arousal in persons with borderline personality disorder. Feeling out of control, they respond by trying to get in control, including attempts to control the therapist.
Similarly, they see attempts to get them to change their behavior as invalidating their experiences or, worse, who they are. Intense emotions aroused by the message they hear—that they are the source of their problems—impair learning and intensify their efforts to gain control. In a battle for control, collaboration and therapy cannot occur.
Case example. Ms. K wants you to understand how difficult her life is because of difficulties with her boss. You start talking about what Ms. K can do to change the situation, without acknowledging how difficult it is to deal with her boss.
Ms. K feels upset and says you don’t understand. For her, the interaction has led to emotion dysregulation and impaired cognitive processing.
Pitfalls with emphasizing acceptance. Most persons who come to therapy very distressed want something in their lives to change. If your primary message is acceptance instead of change, they may lose confidence in you.
Case example. Ms. K wants help dealing with her boss, who is making life quite difficult. As her therapist, you respond with warmth and acceptance but offer no suggestions as to how she might change the situation. Ms. K likes the way you listen to her but abandons therapy. after several sessions.
At first, patients with borderline personality disorder may like the warmth of client-centered acceptance approaches. Over time, however, they may feel their therapy sessions are out of control. They may think the therapist doesn’t understand the situation, doesn’t know how to help, or that situations that are troubling them cannot be changed.
Balanced therapy. DBT solves the change-or-acceptance dilemma by attempting to help patients with borderline personality disorder change themselves and their lives while offering strategies for accepting themselves and their situations.1,2 DBT includes problem-solving and acceptance strategies (Table 2).
Table 2
Strategies used in dialectical behavioral therapy
| Structural strategies | Organization of sessions, attending to the treatment hierarchy, reviewing progress, checking on other modes of therapy |
| Problem assessment strategies | Defining problems with specificity, conducting chain analyses, developing and testing hypotheses |
| Problem solving strategies | Providing didactic information, generating and evaluating solutions, teaching skills and coaching on use of skills, generalizing skills to the real-world environment |
| Contingency management | Use of reinforcement, extinction, aversive contingencies, and principles of shaping. |
| Exposure-based procedures | Both formal and informal |
| Cognitive strategies | Contingency clarification, observation and description of cognitions, cognitive modification |
| Validation strategies | Appearing interested, accurately reflecting, correctly articulating things that have not been fully expressed, explaining behavior in terms of learning history or biological factors, acknowledging validity of responses in terms of current events, interacting in a radically genuine manner, communicating belief in the patient |
| Reciprocal communication strategies | Being responsive, expressing warm engagement, being nonjudgmental, using self-disclosure, maintaining a reasonable power equilibrium |
| Irreverent strategies | Engaging in a matter-of-fact manner, directly confronting dysfunctional behavior, using unexpected, irreverent or humorous responses |
| Dialectical strategies | Using a balanced style, balancing acceptance-oriented strategies with change-oriented strategies, magnifying tension, using metaphor, modeling dialectical thinking and behaviors, moving with speed and flow. |
| Case management strategies | Following a model of consultation to the patient when long-term outcome is more important than short-term outcome; intervening in the patient's environment when short-term outcome is more important than long-term outcome |
DBT’S 4 THERAPY STAGES
DBT is a comprehensive treatment. The original outpatient model for borderline personality disorder (Table 3) has been adapted to different settings and applied to other populations.
Outpatients meet weekly in individual psychotherapy and a skills training group.3 Therapists also meet weekly in a consultation team viewed as “therapy for the therapist.”
Between sessions, therapists consult with patients by telephone to:
- decrease suicide crisis behaviors
- increase generalization of behavioral skills
- decrease patients’ feelings of conflict, alienation, or distance with the therapist.
Four stages. DBT follows four stages. For persons with borderline personality disorder, researchers have evaluated the efficacy of stage-1 therapy. Studies on stage-3 DBT have been conducted with nonborderline-personality individuals with eating disorders. The goals at each stage are:
Stage 1. Move from severe behavioral dyscontrol to behavioral control. Decrease suicidal and other life-threatening behaviors and those that interfere with therapy and quality of life. Increase mindfulness, tolerance for distress, interpersonal effectiveness, and emotion regulation.
Stage 2. Move from quiet desperation to emotional experiencing.
Stage 3. Address problems in living, and move toward ordinary happiness/unhappiness.
Stage 4. Move from incompleteness to capacity for joy and freedom.
Seven randomized controlled trials have shown that DBT can be useful in treating borderline personality disorder.4-10 The initial trial by Linehan et al4 included 47 women ages 18 to 45 who met criteria for borderline personality disorder and had at least two parasuicide incidents in the previous 5 years, with one in the previous 8 weeks. Treatment lasted 1 year, and subjects agreed to stop other individual psychotherapy if assigned to DBT.
Subjects were then randomly assigned to either DBT or “treatment as usual” in the community. In the various DBT studies, treatment-as-usual has included community therapists, Department of Veterans Affairs outpatient treatment, client-centered therapy, and treatment by persons identified by their peers as experts in their communities.
Subjects were assessed every 4 months while in treatment and for 1 year thereafter. DBT was more effective than usual treatment in:
- reducing suicide attempts and self-injury
- decreasing premature dropout from therapy
- reducing emergency room admissions and length of psychiatric hospitalization
- reducing drug abuse, depression, hopelessness, and anger.
Table 3
Modes of therapy in outpatient dialectical behavioral therapy
| Therapeutic goals | Mode |
|---|---|
| Improve motivational factors | Individual psychotherapy |
| Enhance capabilities | Skills training |
| Ensure generalization to natural environment | Between-session consultation |
| Enhance therapist capabilities and motivation to treat effectively | Therapist consultation team |
| Structure the environment | Consultation to the patient |
RECOMMENDATIONS
Some psychiatrists may find “borderline patients” frustrating and unpleasant to treat. DBT therapists, however, make two assumptions that can help anyone working with individuals with borderline personality disorder. To avoid falling into the trap of polarization with these patients, assume that:
- they are doing the best they can
- their efforts are insufficient to meet their needs.
They therefore need to do better, and the therapist’s job is to help them do so. Also assume that if you try to help a patient with borderline personality disorder, you will need help, too. We require DBT therapists to participate in consultation teams.
Training. DBT is a comprehensive program that requires familiarity with the manuals mentioned in this article (see Related resources). Some teams have learned DBT through self-study and consultation with other teams.
If you plan to offer DBT to patients with borderline personality disorder, we recommend that you be:
- trained in behavior therapy and CBT
- familiar with research on emotions and processes involved in emotion regulation.
If you have not had CBT training, find a behavior therapist to join your team or get consultation from a behavior therapist.
An intensive training course in DBT—with 2 weeks of instruction and case consultation and several months of consultation with someone well-versed in DBT—is an efficient way to become familiar with the most critical principles of the treatment. If you cannot train toward adherent delivery of individual therapy, we recommend referring patients to someone trained in DBT.
- Lieb K, Zanarini MC, Schmahl C, et al. Borderline personality disorder. Lancet 2004;364(9432):453-61.
- University of Washington, Behavioral Research and Therapy Clinics. www.brtc.psych.washington.edu/frameResearch.htm;
www.brtc.psych.washington.edu/framePublications.htm - Behavioral Tech, LLC. Consultation and training in dialectical behavioral therapy. www.behavioraltech.org.
Disclosures
Dr. DuBose is president and CEO/co-owner of DBT Center of Seattle, PLLC, and a speaker for Behavioral Tech, LLC.
Dr. Linehan is a shareholder in Behavioral Tech Research, Inc., which develops computerized training for DBT, a DBT trainer for Behavioral Tech, LLC, and the author of two books on DBT. She also receives research grants from the National Institute of Mental Health and National Institute on Drug Abuse.
1. Lynch TR, Chapman AL, Rosenthal MZ, et al. Mechanisms of change in dialectical behavior therapy: theoretical and empirical observations. J Clin Psychol 2005 (in press).
2. Linehan MM. Cognitive-behavioral treatment of borderline personality disorder. New York: Guilford Press, 1993.
3. Linehan MM. Skills training manual for treating borderline personality disorder. New York: Guilford Press, 1993.
4. Linehan MM, Armstrong HE, Suarez A, et al. Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Arch Gen Psychiatry 1991 Dec;48(12):1060-4.
5. Linehan MM, Schmidt HI, Dimeff LA, et al. Dialectical behavior therapy for patients with border-line personality disorder and drug-dependence. Am J Addict 1999;8:279-92.
6. Linehan MM, Dimeff LA, Reynolds SK, et al. Dialectical behavior therapy versus comprehensive validation therapy plus 12-step for the treatment of opioid dependent women meeting criteria for borderline personality disorder. Drug Alcohol Depend 2002;67(1):13-26.
7. Turner RM. Naturalistic evaluation of dialectical behavior therapy-oriented treatment for borderline personality disorders. Cognit Behav Pract 2000;7:413-19.
8. Koons CR, Robins CJ, Tweed JL, et al. Efficacy of dialectical behavior therapy in women veterans with borderline personality disorder. Behav Ther 2001;32:371-90.
9. Verheul R, Van Den Bosch LM, Koeter MW, et al. Dialectical behaviour therapy for women with borderline personality disorder: 12-month, randomised clinical trial in The Netherlands. Br J Psychiatry 2003;182:135-40.
10. Linehan MM, Comtois KA, Brown M, et al. DBT versus nonbehavioral treatment by experts in the community: clinical outcomes. Symposium presentation for the Association for Advancement of Behavior Therapy. University of Washington, Reno NV, 2002.
1. Lynch TR, Chapman AL, Rosenthal MZ, et al. Mechanisms of change in dialectical behavior therapy: theoretical and empirical observations. J Clin Psychol 2005 (in press).
2. Linehan MM. Cognitive-behavioral treatment of borderline personality disorder. New York: Guilford Press, 1993.
3. Linehan MM. Skills training manual for treating borderline personality disorder. New York: Guilford Press, 1993.
4. Linehan MM, Armstrong HE, Suarez A, et al. Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Arch Gen Psychiatry 1991 Dec;48(12):1060-4.
5. Linehan MM, Schmidt HI, Dimeff LA, et al. Dialectical behavior therapy for patients with border-line personality disorder and drug-dependence. Am J Addict 1999;8:279-92.
6. Linehan MM, Dimeff LA, Reynolds SK, et al. Dialectical behavior therapy versus comprehensive validation therapy plus 12-step for the treatment of opioid dependent women meeting criteria for borderline personality disorder. Drug Alcohol Depend 2002;67(1):13-26.
7. Turner RM. Naturalistic evaluation of dialectical behavior therapy-oriented treatment for borderline personality disorders. Cognit Behav Pract 2000;7:413-19.
8. Koons CR, Robins CJ, Tweed JL, et al. Efficacy of dialectical behavior therapy in women veterans with borderline personality disorder. Behav Ther 2001;32:371-90.
9. Verheul R, Van Den Bosch LM, Koeter MW, et al. Dialectical behaviour therapy for women with borderline personality disorder: 12-month, randomised clinical trial in The Netherlands. Br J Psychiatry 2003;182:135-40.
10. Linehan MM, Comtois KA, Brown M, et al. DBT versus nonbehavioral treatment by experts in the community: clinical outcomes. Symposium presentation for the Association for Advancement of Behavior Therapy. University of Washington, Reno NV, 2002.
Metabolic syndrome: 5 risk factors guide therapy
At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?
This article answers those questions by addressing:
- clinical guidelines for diagnosing metabolic syndrome
- suggested intervals for monitoring at-risk patients
- strategies for managing metabolic abnormalities with lifestyle changes or medication.
CASE REPORT: 'FAT' AND FRUSTRATED
Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.
Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.
Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.
The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).
The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.
Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?
IMPLICATIONS OF METABOLIC SYNDROME
Patients with metabolic syndrome are at increased risk for:
In a prospective study that followed 1,209 Finnish men over an average 11.4 years,4 men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.
DEFINING METABOLIC SYNDROME
Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.
According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:
- abdominal obesity
- insulin resistance
- high blood pressure
- elevated triglycerides
- below-normal HDL.
This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).5 The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.
Table 1
5 defined risk factors* for metabolic syndrome
| Risk factor | Clinically significant level |
|---|---|
| Abdominal obesity | |
| Men | Waist circumference >40 in (102 cm) |
| Women | Waist circumference >35 in (88 cm) |
| Blood pressure | |
| Systolic | >130 mm Hg |
| Diastolic | >85 mm Hg |
| HDL count | |
| Men | <40 mg/dL (<1.04 mmol/L) |
| Women | <50 mg/dL (<1.30 mmol/L) |
| Fasting glucose | |
| Men, women | >110 mg/dL (>6.11 mmol/L) |
| Triglycerides | |
| Men, women | >150 mg/dL (>1.70 mmol/L) |
| * If 3 risk factors are present, suspect metabolic syndrome | |
| HDL: high-density lipoprotein cholesterol | |
| Source: Adapted from reference 5. | |
MONITORING FREQUENCY
Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.6
Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).
Table 2
Suggested monitoring intervals for patients taking atypical antipsychotics*
| Baseline | 4 weeks | 8 weeks | 12 weeks | Quarterly | Annually | Every 5 years | |
|---|---|---|---|---|---|---|---|
| Personal/family history | X | X | |||||
| Weight (BMI) | X | X | X | X | X | ||
| Waist circumference | X | X | |||||
| Blood pressure | X | X | X | ||||
| Fasting plasma glucose | X | X | X | ||||
| Fasting lipid profile | X | X | X | ||||
| *Clinical status may warrant more-frequent assessments | |||||||
| BMI: Body mass index | |||||||
| Source: Reference 6. | |||||||
MANAGING METABOLIC PROBLEMS
Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:
- weight management, weight control education, and promoting regular exercise and a healthy diet
- switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
- working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.
Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.
Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.7 Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.7
Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.
Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,2 triglycerides,17 blood pressure,18 and hyperglycemia.19
In one prospective study,20 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.
Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:
- 43% had lower triglycerides than at baseline
- 16% had higher HDL cholesterol
- 38% had lower blood pressure
- 9% had improved fasting glucose
- 28% reduced their waist circumference.
Table 3
Interventions for specific metabolic complications
| Metabolic complication | Nondrug interventions8 | Medications |
|---|---|---|
| Abdominal obesity | Encourage weight loss | Sibutramine*† |
| Increase physical activity | Appetite suppressant | |
| Orlistat*† | ||
| Lipase inhibitor | ||
| Hypertriglyceridemia | Encourage weight loss | Fibrates9* |
| Increase physical activity | Reduce fasting and postprandial triglycerides 20% to 50% | |
| Increase low-glycemic-index food intake | Shift small dense LDL to large buoyant particles | |
| Reduce total carbohydrate intake | Increase HDL particles 10% to 35% | |
| Increase consumption of omega-3 fatty acids | Nicotinic acid10 | |
| Limit alcohol consumption | Reduces triglycerides 20% to 50% | |
| Statins11 | ||
| Reduce fasting and postprandial triglycerides 7% to 30% | ||
| Reduce LDL particles | ||
| Increase HDL particles | ||
| Reduce major coronary vascular events | ||
| Low HDL | Encourage weight loss | Nicotinic acid* |
| Increase physical activity | Increases HDL particles 15% to 35% | |
| Stop smoking | Fibrates9 | |
| Increase monounsaturated fat intake | See above | |
| Statins11 | ||
| See above | ||
| Hypertension | Encourage weight loss | ACE inhibitors* |
| Increase physical activity | May slow progression to diabetes12 | |
| Reduce saturated fat intake | Decrease CVD events13 | |
| Reduce sodium intake | Delay progression of microalbuminuria13 | |
| Limit alcohol consumption | Angiotensin receptor blockers | |
| May improve dyslipidemia associated with metabolic syndrome14 | ||
| Delay progression of microalbuminuria13 | ||
| Hyperglycemia | Encourage weight loss | Metformin,* thiazolidinediones |
| Increase physical activity | Slow progression to diabetes in persons with insulin resistance15,16 (metformin less effective than lifestyle changes)15 | |
| Reduce total carbohydrates | ||
| * Suggested first-line therapy. | ||
| † For patients with BMI 30 kg/m2 | ||
| ACE: Angiotensin-converting enzyme | ||
| CVD: Cardiovascular disease | ||
| HDL: High-density lipoprotein cholesterol | ||
| LDL: Low-density lipoprotein cholesterol | ||
Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.
By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.21
In a prospective 12-month trial,22 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.22
Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).
Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.
Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).6
Table 4
Atypical antipsychotics and their propensity for causing metabolic abnormalities
| Drug | Weight gain | Hyperglycemia | Dyslipidemia |
|---|---|---|---|
| Clozapine | High | High | High |
| Olanzapine | High | High | High |
| Risperidone | Medium | Medium | Low |
| Quetiapine | Medium | Medium | High |
| Aripiprazole | Low | Low | Low |
| Ziprasidone | Low | Low | Low |
| Source: Reference 6 | |||
Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).
Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.25 Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).
CASE CONTINUED: 10 LBS IN 10 WEEKS
At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).
Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.
Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.
- National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
- Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
- National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
- Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.
Drug brand names
- Aripiprazole • Abilify
- Clozapine • Clozaril
- Metformin • Glucophage
- Olanzapine • Zyprexa
- Orlistat • Xenical
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sibutramine • Meridia
- Ziprasidone • Geodon
Disclosure
Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.
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21. Littrell KH, Hilligoss NM, Kirshner CD, et al. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh 2003;35:237-41.
22. Menza M, Vreeland B, Minsky S, et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J Clin Psychiatry 2004;65:471-7.
23. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review and naturalistic, open-label treatment. J Clin Psychiatry 2004;65:110-13.
24. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003;166:391-9.
25. Wong ND, Pio J, Franklin SS, et al. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003;91:1421-6.
At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?
This article answers those questions by addressing:
- clinical guidelines for diagnosing metabolic syndrome
- suggested intervals for monitoring at-risk patients
- strategies for managing metabolic abnormalities with lifestyle changes or medication.
CASE REPORT: 'FAT' AND FRUSTRATED
Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.
Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.
Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.
The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).
The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.
Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?
IMPLICATIONS OF METABOLIC SYNDROME
Patients with metabolic syndrome are at increased risk for:
In a prospective study that followed 1,209 Finnish men over an average 11.4 years,4 men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.
DEFINING METABOLIC SYNDROME
Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.
According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:
- abdominal obesity
- insulin resistance
- high blood pressure
- elevated triglycerides
- below-normal HDL.
This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).5 The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.
Table 1
5 defined risk factors* for metabolic syndrome
| Risk factor | Clinically significant level |
|---|---|
| Abdominal obesity | |
| Men | Waist circumference >40 in (102 cm) |
| Women | Waist circumference >35 in (88 cm) |
| Blood pressure | |
| Systolic | >130 mm Hg |
| Diastolic | >85 mm Hg |
| HDL count | |
| Men | <40 mg/dL (<1.04 mmol/L) |
| Women | <50 mg/dL (<1.30 mmol/L) |
| Fasting glucose | |
| Men, women | >110 mg/dL (>6.11 mmol/L) |
| Triglycerides | |
| Men, women | >150 mg/dL (>1.70 mmol/L) |
| * If 3 risk factors are present, suspect metabolic syndrome | |
| HDL: high-density lipoprotein cholesterol | |
| Source: Adapted from reference 5. | |
MONITORING FREQUENCY
Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.6
Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).
Table 2
Suggested monitoring intervals for patients taking atypical antipsychotics*
| Baseline | 4 weeks | 8 weeks | 12 weeks | Quarterly | Annually | Every 5 years | |
|---|---|---|---|---|---|---|---|
| Personal/family history | X | X | |||||
| Weight (BMI) | X | X | X | X | X | ||
| Waist circumference | X | X | |||||
| Blood pressure | X | X | X | ||||
| Fasting plasma glucose | X | X | X | ||||
| Fasting lipid profile | X | X | X | ||||
| *Clinical status may warrant more-frequent assessments | |||||||
| BMI: Body mass index | |||||||
| Source: Reference 6. | |||||||
MANAGING METABOLIC PROBLEMS
Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:
- weight management, weight control education, and promoting regular exercise and a healthy diet
- switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
- working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.
Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.
Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.7 Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.7
Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.
Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,2 triglycerides,17 blood pressure,18 and hyperglycemia.19
In one prospective study,20 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.
Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:
- 43% had lower triglycerides than at baseline
- 16% had higher HDL cholesterol
- 38% had lower blood pressure
- 9% had improved fasting glucose
- 28% reduced their waist circumference.
Table 3
Interventions for specific metabolic complications
| Metabolic complication | Nondrug interventions8 | Medications |
|---|---|---|
| Abdominal obesity | Encourage weight loss | Sibutramine*† |
| Increase physical activity | Appetite suppressant | |
| Orlistat*† | ||
| Lipase inhibitor | ||
| Hypertriglyceridemia | Encourage weight loss | Fibrates9* |
| Increase physical activity | Reduce fasting and postprandial triglycerides 20% to 50% | |
| Increase low-glycemic-index food intake | Shift small dense LDL to large buoyant particles | |
| Reduce total carbohydrate intake | Increase HDL particles 10% to 35% | |
| Increase consumption of omega-3 fatty acids | Nicotinic acid10 | |
| Limit alcohol consumption | Reduces triglycerides 20% to 50% | |
| Statins11 | ||
| Reduce fasting and postprandial triglycerides 7% to 30% | ||
| Reduce LDL particles | ||
| Increase HDL particles | ||
| Reduce major coronary vascular events | ||
| Low HDL | Encourage weight loss | Nicotinic acid* |
| Increase physical activity | Increases HDL particles 15% to 35% | |
| Stop smoking | Fibrates9 | |
| Increase monounsaturated fat intake | See above | |
| Statins11 | ||
| See above | ||
| Hypertension | Encourage weight loss | ACE inhibitors* |
| Increase physical activity | May slow progression to diabetes12 | |
| Reduce saturated fat intake | Decrease CVD events13 | |
| Reduce sodium intake | Delay progression of microalbuminuria13 | |
| Limit alcohol consumption | Angiotensin receptor blockers | |
| May improve dyslipidemia associated with metabolic syndrome14 | ||
| Delay progression of microalbuminuria13 | ||
| Hyperglycemia | Encourage weight loss | Metformin,* thiazolidinediones |
| Increase physical activity | Slow progression to diabetes in persons with insulin resistance15,16 (metformin less effective than lifestyle changes)15 | |
| Reduce total carbohydrates | ||
| * Suggested first-line therapy. | ||
| † For patients with BMI 30 kg/m2 | ||
| ACE: Angiotensin-converting enzyme | ||
| CVD: Cardiovascular disease | ||
| HDL: High-density lipoprotein cholesterol | ||
| LDL: Low-density lipoprotein cholesterol | ||
Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.
By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.21
In a prospective 12-month trial,22 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.22
Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).
Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.
Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).6
Table 4
Atypical antipsychotics and their propensity for causing metabolic abnormalities
| Drug | Weight gain | Hyperglycemia | Dyslipidemia |
|---|---|---|---|
| Clozapine | High | High | High |
| Olanzapine | High | High | High |
| Risperidone | Medium | Medium | Low |
| Quetiapine | Medium | Medium | High |
| Aripiprazole | Low | Low | Low |
| Ziprasidone | Low | Low | Low |
| Source: Reference 6 | |||
Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).
Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.25 Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).
CASE CONTINUED: 10 LBS IN 10 WEEKS
At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).
Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.
Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.
- National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
- Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
- National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
- Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.
Drug brand names
- Aripiprazole • Abilify
- Clozapine • Clozaril
- Metformin • Glucophage
- Olanzapine • Zyprexa
- Orlistat • Xenical
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sibutramine • Meridia
- Ziprasidone • Geodon
Disclosure
Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.
At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?
This article answers those questions by addressing:
- clinical guidelines for diagnosing metabolic syndrome
- suggested intervals for monitoring at-risk patients
- strategies for managing metabolic abnormalities with lifestyle changes or medication.
CASE REPORT: 'FAT' AND FRUSTRATED
Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.
Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.
Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.
The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).
The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.
Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?
IMPLICATIONS OF METABOLIC SYNDROME
Patients with metabolic syndrome are at increased risk for:
In a prospective study that followed 1,209 Finnish men over an average 11.4 years,4 men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.
DEFINING METABOLIC SYNDROME
Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.
According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:
- abdominal obesity
- insulin resistance
- high blood pressure
- elevated triglycerides
- below-normal HDL.
This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).5 The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.
Table 1
5 defined risk factors* for metabolic syndrome
| Risk factor | Clinically significant level |
|---|---|
| Abdominal obesity | |
| Men | Waist circumference >40 in (102 cm) |
| Women | Waist circumference >35 in (88 cm) |
| Blood pressure | |
| Systolic | >130 mm Hg |
| Diastolic | >85 mm Hg |
| HDL count | |
| Men | <40 mg/dL (<1.04 mmol/L) |
| Women | <50 mg/dL (<1.30 mmol/L) |
| Fasting glucose | |
| Men, women | >110 mg/dL (>6.11 mmol/L) |
| Triglycerides | |
| Men, women | >150 mg/dL (>1.70 mmol/L) |
| * If 3 risk factors are present, suspect metabolic syndrome | |
| HDL: high-density lipoprotein cholesterol | |
| Source: Adapted from reference 5. | |
MONITORING FREQUENCY
Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.6
Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).
Table 2
Suggested monitoring intervals for patients taking atypical antipsychotics*
| Baseline | 4 weeks | 8 weeks | 12 weeks | Quarterly | Annually | Every 5 years | |
|---|---|---|---|---|---|---|---|
| Personal/family history | X | X | |||||
| Weight (BMI) | X | X | X | X | X | ||
| Waist circumference | X | X | |||||
| Blood pressure | X | X | X | ||||
| Fasting plasma glucose | X | X | X | ||||
| Fasting lipid profile | X | X | X | ||||
| *Clinical status may warrant more-frequent assessments | |||||||
| BMI: Body mass index | |||||||
| Source: Reference 6. | |||||||
MANAGING METABOLIC PROBLEMS
Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:
- weight management, weight control education, and promoting regular exercise and a healthy diet
- switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
- working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.
Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.
Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.7 Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.7
Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.
Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,2 triglycerides,17 blood pressure,18 and hyperglycemia.19
In one prospective study,20 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.
Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:
- 43% had lower triglycerides than at baseline
- 16% had higher HDL cholesterol
- 38% had lower blood pressure
- 9% had improved fasting glucose
- 28% reduced their waist circumference.
Table 3
Interventions for specific metabolic complications
| Metabolic complication | Nondrug interventions8 | Medications |
|---|---|---|
| Abdominal obesity | Encourage weight loss | Sibutramine*† |
| Increase physical activity | Appetite suppressant | |
| Orlistat*† | ||
| Lipase inhibitor | ||
| Hypertriglyceridemia | Encourage weight loss | Fibrates9* |
| Increase physical activity | Reduce fasting and postprandial triglycerides 20% to 50% | |
| Increase low-glycemic-index food intake | Shift small dense LDL to large buoyant particles | |
| Reduce total carbohydrate intake | Increase HDL particles 10% to 35% | |
| Increase consumption of omega-3 fatty acids | Nicotinic acid10 | |
| Limit alcohol consumption | Reduces triglycerides 20% to 50% | |
| Statins11 | ||
| Reduce fasting and postprandial triglycerides 7% to 30% | ||
| Reduce LDL particles | ||
| Increase HDL particles | ||
| Reduce major coronary vascular events | ||
| Low HDL | Encourage weight loss | Nicotinic acid* |
| Increase physical activity | Increases HDL particles 15% to 35% | |
| Stop smoking | Fibrates9 | |
| Increase monounsaturated fat intake | See above | |
| Statins11 | ||
| See above | ||
| Hypertension | Encourage weight loss | ACE inhibitors* |
| Increase physical activity | May slow progression to diabetes12 | |
| Reduce saturated fat intake | Decrease CVD events13 | |
| Reduce sodium intake | Delay progression of microalbuminuria13 | |
| Limit alcohol consumption | Angiotensin receptor blockers | |
| May improve dyslipidemia associated with metabolic syndrome14 | ||
| Delay progression of microalbuminuria13 | ||
| Hyperglycemia | Encourage weight loss | Metformin,* thiazolidinediones |
| Increase physical activity | Slow progression to diabetes in persons with insulin resistance15,16 (metformin less effective than lifestyle changes)15 | |
| Reduce total carbohydrates | ||
| * Suggested first-line therapy. | ||
| † For patients with BMI 30 kg/m2 | ||
| ACE: Angiotensin-converting enzyme | ||
| CVD: Cardiovascular disease | ||
| HDL: High-density lipoprotein cholesterol | ||
| LDL: Low-density lipoprotein cholesterol | ||
Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.
By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.21
In a prospective 12-month trial,22 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.22
Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).
Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.
Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).6
Table 4
Atypical antipsychotics and their propensity for causing metabolic abnormalities
| Drug | Weight gain | Hyperglycemia | Dyslipidemia |
|---|---|---|---|
| Clozapine | High | High | High |
| Olanzapine | High | High | High |
| Risperidone | Medium | Medium | Low |
| Quetiapine | Medium | Medium | High |
| Aripiprazole | Low | Low | Low |
| Ziprasidone | Low | Low | Low |
| Source: Reference 6 | |||
Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).
Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.25 Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).
CASE CONTINUED: 10 LBS IN 10 WEEKS
At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).
Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.
Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.
- National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
- Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
- National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
- Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.
Drug brand names
- Aripiprazole • Abilify
- Clozapine • Clozaril
- Metformin • Glucophage
- Olanzapine • Zyprexa
- Orlistat • Xenical
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sibutramine • Meridia
- Ziprasidone • Geodon
Disclosure
Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.
1. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992;41:715-22.
2. Isomma B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.
3. Trevisan M, Liu J, Bahsas FB, Menotti A. Syndrome X and mortality: a population-based study. Am J Epidemiol 1998;148:958-66.
4. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.
5. National Institutes of Health: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III). Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
6. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596-601.
7. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res 1998;6(suppl 2):51S-209S.
8. Darwin D. Metabolic syndrome: time for action. Am Fam Physician 2004;69:2875-82.
9. Maki KC. Fibrates for treatment of the metabolic syndrome. Curr Atheroscler Rep 2004;6:45-51.
10. Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18:278-85.
11. Showers JR. Effects of statins on the vasculature: implications for aggressive lipid management in the cardiovascular metabolic syndrome. Am J Cardiol 2003;91(suppl):14B-22B.
12. Yusuf S, Gerstein H, Hoogwerf B, et al. for the HOPE Study Investigators. Ramipril and the development of diabetes. JAMA 2001;286:1882-5.
13. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care 2003;26(suppl 1):S80-S82.
14. Derosa G, Cicero AF, Bertone G, et al. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized double-blind study. Clin Ther 2004;26:1228-36.
15. Diabetes prevention program research group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
16. Buchanan T, Xiang A, Peters R, et al. Prevention of type 2 diabetes by treatment of insulin resistance: comparison of early vs. late in the TRIPOD study [abstract]. Diabetes 2002;51(suppl 2):A35.-
17. Leon AS, Sanchez O. Meta-analysis of the effects of aerobic exercise training on blood lipids. Circulation 2001;104(suppl II):414-15 (abstract).
18. Fagard RH. Exercise characteristics and blood pressure response to dynamic physical training. Med Sci Sports Exerc 2001;33(6 suppl):S484-S492.
19. Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001;33(6 suppl):S438-S445.
20. Katzmarzyk PT, Leon AS, Wilmore JH, et al. Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study. Med Sci Sports Exerc 2003;35:1703-9.
21. Littrell KH, Hilligoss NM, Kirshner CD, et al. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh 2003;35:237-41.
22. Menza M, Vreeland B, Minsky S, et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J Clin Psychiatry 2004;65:471-7.
23. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review and naturalistic, open-label treatment. J Clin Psychiatry 2004;65:110-13.
24. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003;166:391-9.
25. Wong ND, Pio J, Franklin SS, et al. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003;91:1421-6.
1. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992;41:715-22.
2. Isomma B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.
3. Trevisan M, Liu J, Bahsas FB, Menotti A. Syndrome X and mortality: a population-based study. Am J Epidemiol 1998;148:958-66.
4. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.
5. National Institutes of Health: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III). Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
6. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596-601.
7. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res 1998;6(suppl 2):51S-209S.
8. Darwin D. Metabolic syndrome: time for action. Am Fam Physician 2004;69:2875-82.
9. Maki KC. Fibrates for treatment of the metabolic syndrome. Curr Atheroscler Rep 2004;6:45-51.
10. Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18:278-85.
11. Showers JR. Effects of statins on the vasculature: implications for aggressive lipid management in the cardiovascular metabolic syndrome. Am J Cardiol 2003;91(suppl):14B-22B.
12. Yusuf S, Gerstein H, Hoogwerf B, et al. for the HOPE Study Investigators. Ramipril and the development of diabetes. JAMA 2001;286:1882-5.
13. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care 2003;26(suppl 1):S80-S82.
14. Derosa G, Cicero AF, Bertone G, et al. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized double-blind study. Clin Ther 2004;26:1228-36.
15. Diabetes prevention program research group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
16. Buchanan T, Xiang A, Peters R, et al. Prevention of type 2 diabetes by treatment of insulin resistance: comparison of early vs. late in the TRIPOD study [abstract]. Diabetes 2002;51(suppl 2):A35.-
17. Leon AS, Sanchez O. Meta-analysis of the effects of aerobic exercise training on blood lipids. Circulation 2001;104(suppl II):414-15 (abstract).
18. Fagard RH. Exercise characteristics and blood pressure response to dynamic physical training. Med Sci Sports Exerc 2001;33(6 suppl):S484-S492.
19. Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001;33(6 suppl):S438-S445.
20. Katzmarzyk PT, Leon AS, Wilmore JH, et al. Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study. Med Sci Sports Exerc 2003;35:1703-9.
21. Littrell KH, Hilligoss NM, Kirshner CD, et al. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh 2003;35:237-41.
22. Menza M, Vreeland B, Minsky S, et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J Clin Psychiatry 2004;65:471-7.
23. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review and naturalistic, open-label treatment. J Clin Psychiatry 2004;65:110-13.
24. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003;166:391-9.
25. Wong ND, Pio J, Franklin SS, et al. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003;91:1421-6.
Using IM antipsychotics: Lessons from clinical practice
Knowing how to use IM risperidone—and other long-acting atypicals that are likely to be approved—will enable you to help your patients benefit from reliable antipsychotic dosing. Long-acting antipsychotics address the challenge that makes schizophrenia particularly difficult to treat: medication nonadherence because of psychotic illness’ effect on insight, reality testing, and motivation.1,2
Too few schizophrenia patients in the United States—perhaps <5% of appropriate candidates—receive depot antipsychotics.1 We believe these agents provide the best delivery system to our patients and welcome IM risperidone’s approval3
This article shares what we have learned from research and clinical practice about using injectable antipsychotics, with a focus on how to effectively use long-acting IM risperidone.
CONVENTIONAL ANTIPSYCHOTICS
Once seen as an improvement over oral conventional antipsychotics, IM agents were relegated over time to a means of coercion (as in, “If you don’t take your medicine orally, we’ll force you to take a shot.”). Oral atypical antipsychotics, with improved side-effect profiles and possibly reduced relapse risk, also discouraged psychiatrists from using long-acting conventional antipsychotics as first-line medication.4
Available agents. Fluphenazine and haloperidol—the two long-acting conventional antipsychotics available in the United States (Table 1)—are esterified to a fatty acid (oil) to create an IM injectable prodrug. They can be given in gluteal or deltoid injection, although doses >2 cc should be given in the gluteus.
Hydrolysis releases the active drug, usually within 3 days. This interval allows loading doses to reach therapeutic blood levels rapidly when the goal is to stabilize patients in the hospital or during a short-term crisis stay. Disadvantages include:
- pain and lasting reactions at the injection site
- risk of extrapyramidal symptoms (EPS), neuroleptic malignant syndrome, and tardive dyskinesia.5
Table 1
Administering long-acting injectable antipsychotics
| Name | Preparation | Dose range | Interval | Injection site | Comment |
|---|---|---|---|---|---|
| Fluphenazine | 25 mg/mL | 5 to 75 mg each injection | Every 1 to 2 weeks | Deltoid or gluteal | Site reaction common |
| Haloperidol | 50 or 100 mg/mL | 25 to 200 mg each injection | Every 2 to 4 weeks | Deltoid or gluteal | Site reaction common |
| Risperidone | 25, 37.5, or 50 mg in prefilled bottles | 25 to 50 mg each injection | Every 2 weeks | Gluteal only | Requires reconstitution, proprietary kit |
Depot administration. Fluphenazine depot is commonly given every 2 weeks, starting with 25 mg, but a weekly or monthly interval is not rare. The dose range is broad because the drug can be given in fine gradations from as low as 2.5 mg (0.1 cc) to 75 mg (3 cc). Thus, you can individually titrate it by varying the dose and/or interval.
Because haloperidol is usually given monthly and thus requires less-frequent dosing, it tends to be used more often than fluphenazine. Haloperidol can be given in shorter intervals but is rarely used at intervals >4 weeks. Usual dosing is 50 to 100 mg per shot but can range from small amounts to hundreds of milligrams.
Transition from oral to IM. Switching from an oral antipsychotic to a long-acting medication is straightforward. As long as test doses or history predetermine that patients have no untoward effects from fluphenazine or haloperidol, the first injection can be given and the oral agent maintained for 3 to 5 days.
Monitor for dystonias and other emergent EPS. Some practitioners pretreat with anticholinergics to avoid these neurologic side effects. If you can monitor the patient over the first week, you can often avoid pretreatment and add side-effect medication as needed.
LONG-ACTING IM RISPERIDONE
For technical and approval reasons, it took nearly a decade for a long-acting atypical to be developed and approved. Because risperidone could not easily be attached to an oil, the solution to making risperidone long-acting was to use microspheres.6
Microspheres are best conceptualized as a solid sphere of dissolvable suture-like material (glycolide-lactide polymers) embedded with risperidone bits. The microspheres are packaged dry and reconstituted at the clinic with aqueous diluent at the time of medication. Once reconstituted, it forms a suspension of microspheres in water.
‘Snow in a snow globe.’ Reconstituted long-acting risperidone appears like snow in a snow globe. With shaking, the microspheres become suspended but quickly settle in the bottle or syringe. Shake to resuspend the microspheres if you are giving an injection more than 2 minutes after the initial reconstitution. Reconstituted microspheres can be given up to 6 hours after hydration.
Transfer the medication to the syringe via the proprietary exchange system, and use the specialized needle to inject the medication into the gluteal region. Once injected, the microspheres swell with water from local muscle, then break down.
Delayed action. The microspheres begin releasing risperidone in 3 to 4 weeks. Therapeutic levels last approximately 2 weeks until the microspheres gradually convert to carbon dioxide and water. This delayed action requires coverage with oral or other depot medication. Coverage is no longer needed after the medication reaches a steady state (Figure).
Tolerability. As with any long-acting antipsychotic, establish riperidone’s tolerability by history or test dosing. No set number of doses will ensure that a patient won’t have an allergic reaction, but we usually recommend several days of oral dosing before the first injection.
Dosing interval. The approved dosing interval of every 2 weeks should work for most patients. Longer intervals are being studied but are not approved practice.
From oral to IM. Risperidone’s manufacturer recommends at least 3 weeks of coverage by another agent when transitioning from oral to IM to ensure that long-acting risperidone reaches a therapeutic level before being used alone.7 We use even longer coverage—4 to 6 weeks if feasible and acceptable to the patient. We worry more about under-medication than about possible overmedication caused by the overlap. We also consider other factors (Table 2).8
Knowing your patient’s history is critical to ensuring a safe transition. Imagine two patients who are stable on the same antipsychotic dose. When under-medicated during a dose switch, the first recedes into his room and is isolative, whereas the second hits his mother. The first patient will more likely tolerate a quick switch without untoward consequences; the second will need a longer and slower overlap to prevent a recurrence of violent behavior.
Figure Long-acting IM risperidone: Steady-state blood levels by 4th dose
Source: Adapted and reprinted with permission of Robert Lasser from a poster presented at the American Psychiatric Nurses Association annual meeting, Dallas, TX, 2002.Table 2
Switching from another antipsychotic to long-acting IM risperidone
|
DOSING IM RISPERIDONE
Choosing a dose of long-acting risperidone can be difficult. Several points of reference are helpful, but no formula exists. The long-acting form of any antipsychotic behaves differently from its oral counterpart. The maximum daily blood level is lower and the daily trough higher, so that blood levels are governed in a more narrow range. This allows fewer dose- or blood level-related side effects and steadier blood levels.
Dosing equivalents. Long-acting IM risperidone’s preclinical pharmacokinetics data suggested that 25 mg every 2 weeks is equivalent to 2 mg oral per day, 50 mg to 4 mg/d, and 75 mg to 6 mg/d.3 In clinical practice, we find equivalency is broader and represents a range of values. Thus, the 25-mg injection is equivalent to 2 to 4 mg of oral risperidone. Because oral risperidone’s average dose is slightly greater than 4 mg/d, the 25-mg injection should work for most patients.
Side effects. With IM risperidone, the maximum blood level is approximately 30% lower than with the oral dose, so dose-related EPS and prolactin elevation may be less than would be expected for the oral dose range.9 Individual sensitivities do exist, however. We have had some patients experience EPS at low doses and many others not experience EPS at high doses.
Recommendations. If evidence suggests that the patient might be stable on oral doses of 2 to 4 mg/d, start with the 25-mg, every 2-week injection. A recent study in which patients switched directly to long-acting risperidone, without intervening oral risperidone, supports this approach.10
Monitor the patient’s symptoms, being aware that the medication does not begin to take effect until 3 weeks after the first injection. That implies that the second injection is given before you know the efficacy of the first.
We try to maintain the patient on this regimen for several weeks, using oral supplementation if necessary and practical. If the patient requires supplementation throughout the four-injection, 2-month trial, we then:
- increase the dose to 37.5 mg
- repeat the 2-month trial with supplementation as necessary
- and, again, if the patient requires supplementation for the entire 2 months, increase to the 50-mg dose.
This plan requires patience by both clinician and patient but reduces overmedication.
SPECIAL CIRCUMSTANCES
Missed doses. Patients who are stable on a long-acting IM risperidone dose should be maintained indefinitely. As we have all experienced, however, indefinitely is rarely forever. Patients may need periodic dose adjustments or miss doses for a variety of reasons.
We find that patients who are up to a week overdue for an injection are still stable. When a patient arrives more than a week late, check for symptom worsening to determine if you need to supplement the injection with oral medication. If the patient has missed several months, you probably need to restart the initial process.
Inpatient use. Long-acting IM risperidone has been studied in hospitalized patients.11 Getting approval for inpatient use may be difficult, however, if inpatient services and the outpatient pharmacy are on separate budgets.
Though IM risperidone may not take effect until several weeks after a patient’s discharge, starting inpatient treatment may be appropriate. At our institution, we developed tenets for reviewing each case (Table 3).
Before we give any injection, we require that the system for outpatient injections—including place and payment source—be in place. Without these precautions, you may find you are unable to give the next injection at the proper interval.
Table 3
Tenets for using long-acting IM risperidone for inpatients
| If the patient… | Then… |
|---|---|
| is receiving IM risperidone on admission and you decide to continue it | give the dose at the appropriate time if patient will not be discharged within 3 days of the injection appointment |
| is to be started on IM risperidone and to be discharged in <3 days | start treatment as an outpatient |
| is committed to the hospital for >3 weeks | start IM risperidone in the hospital |
| is admitted to be started on IM risperidone because starting as an outpatient has failed | start IM risperidone in the hospital |
Related resources
- Keith SJ, Pani L, Nick B, et al. Practical application of pharmacotherapy with long-acting risperidone for patients with schizophrenia. Psychiatr Serv. 2004;55(9):997-1005.
- Risperdal Consta. Risperidone long-acting injection. Janssen Pharmaceutica. Available at www.risperdalconsta.com. Accessed Feb. 25, 2005.
Drug brand names
- Fluphenazine • Prolixin
- Haloperidol • Haldol
- Risperidone (long-acting) • Risperdal Consta
Disclosure
Dr. Lauriello receives grant/research support from AstraZeneca Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly and Co. He is a consultant to or speaker for Eli Lilly and Co., Janssen Pharmaceutica, Pfizer Inc., and Bristol-Myers Squibb Co.
Dr. Keith is a consultant to or speaker for Bristol-Myers Squibb Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., and Pfizer Inc.
1. Keith SJ, Kane JM. Partial compliance and patient consequences in schizophrenia: our patients can do better. J Clin Psychiatry 2003;64(11):1308-15.
2. Dolder CR, Lacro JP, Dunn LB, et al. Antipsychotic medication adherence: is there a difference between typical and atypical agents? Am J Psychiatry 2002;159(1):103-8.
3. Kane JM, Eerdekens M, Lindenmayer JP, et al. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry 2003;160(6):1125-32.
4. Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002;346(1):16-22.
5. Tandon R, Jibson MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry 2002;14(2):123-9.
6. Ramstack M, Grandolfi G, Mannaert E, et al. Long-acting risperidone: prolonged-release injectable delivery of risperidone using medisorb microsphere technology. Biol Psychiatry 2003;53(suppl 89):204.-
7. Janssen-Cilag Ltd. Product information for Risperdal Consta. Available at: http://www.janssencilag.co.uk (go to products page). Accessed February 3, 2005.
8. Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry 2003;64(10):1250-7.
9. Eerdekens M, Van Hove I, Remmerie B, Mannaert E. Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia. Schizophr Res 2004;70(1):91-100.
10. Lindenmayer JP, Eerdekens E, Berry SA, Eerdekens M. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J Clin Psychiatry 2004;65(8):1084-9.
11. Lauriello J, McEvoy JP, Rodriguez S, et al. Long-acting risperidone vs. placebo in the treatment of hospital inpatients with schizophrenia. Schizophr Res 2005;72(2-3):249-58.
Knowing how to use IM risperidone—and other long-acting atypicals that are likely to be approved—will enable you to help your patients benefit from reliable antipsychotic dosing. Long-acting antipsychotics address the challenge that makes schizophrenia particularly difficult to treat: medication nonadherence because of psychotic illness’ effect on insight, reality testing, and motivation.1,2
Too few schizophrenia patients in the United States—perhaps <5% of appropriate candidates—receive depot antipsychotics.1 We believe these agents provide the best delivery system to our patients and welcome IM risperidone’s approval3
This article shares what we have learned from research and clinical practice about using injectable antipsychotics, with a focus on how to effectively use long-acting IM risperidone.
CONVENTIONAL ANTIPSYCHOTICS
Once seen as an improvement over oral conventional antipsychotics, IM agents were relegated over time to a means of coercion (as in, “If you don’t take your medicine orally, we’ll force you to take a shot.”). Oral atypical antipsychotics, with improved side-effect profiles and possibly reduced relapse risk, also discouraged psychiatrists from using long-acting conventional antipsychotics as first-line medication.4
Available agents. Fluphenazine and haloperidol—the two long-acting conventional antipsychotics available in the United States (Table 1)—are esterified to a fatty acid (oil) to create an IM injectable prodrug. They can be given in gluteal or deltoid injection, although doses >2 cc should be given in the gluteus.
Hydrolysis releases the active drug, usually within 3 days. This interval allows loading doses to reach therapeutic blood levels rapidly when the goal is to stabilize patients in the hospital or during a short-term crisis stay. Disadvantages include:
- pain and lasting reactions at the injection site
- risk of extrapyramidal symptoms (EPS), neuroleptic malignant syndrome, and tardive dyskinesia.5
Table 1
Administering long-acting injectable antipsychotics
| Name | Preparation | Dose range | Interval | Injection site | Comment |
|---|---|---|---|---|---|
| Fluphenazine | 25 mg/mL | 5 to 75 mg each injection | Every 1 to 2 weeks | Deltoid or gluteal | Site reaction common |
| Haloperidol | 50 or 100 mg/mL | 25 to 200 mg each injection | Every 2 to 4 weeks | Deltoid or gluteal | Site reaction common |
| Risperidone | 25, 37.5, or 50 mg in prefilled bottles | 25 to 50 mg each injection | Every 2 weeks | Gluteal only | Requires reconstitution, proprietary kit |
Depot administration. Fluphenazine depot is commonly given every 2 weeks, starting with 25 mg, but a weekly or monthly interval is not rare. The dose range is broad because the drug can be given in fine gradations from as low as 2.5 mg (0.1 cc) to 75 mg (3 cc). Thus, you can individually titrate it by varying the dose and/or interval.
Because haloperidol is usually given monthly and thus requires less-frequent dosing, it tends to be used more often than fluphenazine. Haloperidol can be given in shorter intervals but is rarely used at intervals >4 weeks. Usual dosing is 50 to 100 mg per shot but can range from small amounts to hundreds of milligrams.
Transition from oral to IM. Switching from an oral antipsychotic to a long-acting medication is straightforward. As long as test doses or history predetermine that patients have no untoward effects from fluphenazine or haloperidol, the first injection can be given and the oral agent maintained for 3 to 5 days.
Monitor for dystonias and other emergent EPS. Some practitioners pretreat with anticholinergics to avoid these neurologic side effects. If you can monitor the patient over the first week, you can often avoid pretreatment and add side-effect medication as needed.
LONG-ACTING IM RISPERIDONE
For technical and approval reasons, it took nearly a decade for a long-acting atypical to be developed and approved. Because risperidone could not easily be attached to an oil, the solution to making risperidone long-acting was to use microspheres.6
Microspheres are best conceptualized as a solid sphere of dissolvable suture-like material (glycolide-lactide polymers) embedded with risperidone bits. The microspheres are packaged dry and reconstituted at the clinic with aqueous diluent at the time of medication. Once reconstituted, it forms a suspension of microspheres in water.
‘Snow in a snow globe.’ Reconstituted long-acting risperidone appears like snow in a snow globe. With shaking, the microspheres become suspended but quickly settle in the bottle or syringe. Shake to resuspend the microspheres if you are giving an injection more than 2 minutes after the initial reconstitution. Reconstituted microspheres can be given up to 6 hours after hydration.
Transfer the medication to the syringe via the proprietary exchange system, and use the specialized needle to inject the medication into the gluteal region. Once injected, the microspheres swell with water from local muscle, then break down.
Delayed action. The microspheres begin releasing risperidone in 3 to 4 weeks. Therapeutic levels last approximately 2 weeks until the microspheres gradually convert to carbon dioxide and water. This delayed action requires coverage with oral or other depot medication. Coverage is no longer needed after the medication reaches a steady state (Figure).
Tolerability. As with any long-acting antipsychotic, establish riperidone’s tolerability by history or test dosing. No set number of doses will ensure that a patient won’t have an allergic reaction, but we usually recommend several days of oral dosing before the first injection.
Dosing interval. The approved dosing interval of every 2 weeks should work for most patients. Longer intervals are being studied but are not approved practice.
From oral to IM. Risperidone’s manufacturer recommends at least 3 weeks of coverage by another agent when transitioning from oral to IM to ensure that long-acting risperidone reaches a therapeutic level before being used alone.7 We use even longer coverage—4 to 6 weeks if feasible and acceptable to the patient. We worry more about under-medication than about possible overmedication caused by the overlap. We also consider other factors (Table 2).8
Knowing your patient’s history is critical to ensuring a safe transition. Imagine two patients who are stable on the same antipsychotic dose. When under-medicated during a dose switch, the first recedes into his room and is isolative, whereas the second hits his mother. The first patient will more likely tolerate a quick switch without untoward consequences; the second will need a longer and slower overlap to prevent a recurrence of violent behavior.
Figure Long-acting IM risperidone: Steady-state blood levels by 4th dose
Source: Adapted and reprinted with permission of Robert Lasser from a poster presented at the American Psychiatric Nurses Association annual meeting, Dallas, TX, 2002.Table 2
Switching from another antipsychotic to long-acting IM risperidone
|
DOSING IM RISPERIDONE
Choosing a dose of long-acting risperidone can be difficult. Several points of reference are helpful, but no formula exists. The long-acting form of any antipsychotic behaves differently from its oral counterpart. The maximum daily blood level is lower and the daily trough higher, so that blood levels are governed in a more narrow range. This allows fewer dose- or blood level-related side effects and steadier blood levels.
Dosing equivalents. Long-acting IM risperidone’s preclinical pharmacokinetics data suggested that 25 mg every 2 weeks is equivalent to 2 mg oral per day, 50 mg to 4 mg/d, and 75 mg to 6 mg/d.3 In clinical practice, we find equivalency is broader and represents a range of values. Thus, the 25-mg injection is equivalent to 2 to 4 mg of oral risperidone. Because oral risperidone’s average dose is slightly greater than 4 mg/d, the 25-mg injection should work for most patients.
Side effects. With IM risperidone, the maximum blood level is approximately 30% lower than with the oral dose, so dose-related EPS and prolactin elevation may be less than would be expected for the oral dose range.9 Individual sensitivities do exist, however. We have had some patients experience EPS at low doses and many others not experience EPS at high doses.
Recommendations. If evidence suggests that the patient might be stable on oral doses of 2 to 4 mg/d, start with the 25-mg, every 2-week injection. A recent study in which patients switched directly to long-acting risperidone, without intervening oral risperidone, supports this approach.10
Monitor the patient’s symptoms, being aware that the medication does not begin to take effect until 3 weeks after the first injection. That implies that the second injection is given before you know the efficacy of the first.
We try to maintain the patient on this regimen for several weeks, using oral supplementation if necessary and practical. If the patient requires supplementation throughout the four-injection, 2-month trial, we then:
- increase the dose to 37.5 mg
- repeat the 2-month trial with supplementation as necessary
- and, again, if the patient requires supplementation for the entire 2 months, increase to the 50-mg dose.
This plan requires patience by both clinician and patient but reduces overmedication.
SPECIAL CIRCUMSTANCES
Missed doses. Patients who are stable on a long-acting IM risperidone dose should be maintained indefinitely. As we have all experienced, however, indefinitely is rarely forever. Patients may need periodic dose adjustments or miss doses for a variety of reasons.
We find that patients who are up to a week overdue for an injection are still stable. When a patient arrives more than a week late, check for symptom worsening to determine if you need to supplement the injection with oral medication. If the patient has missed several months, you probably need to restart the initial process.
Inpatient use. Long-acting IM risperidone has been studied in hospitalized patients.11 Getting approval for inpatient use may be difficult, however, if inpatient services and the outpatient pharmacy are on separate budgets.
Though IM risperidone may not take effect until several weeks after a patient’s discharge, starting inpatient treatment may be appropriate. At our institution, we developed tenets for reviewing each case (Table 3).
Before we give any injection, we require that the system for outpatient injections—including place and payment source—be in place. Without these precautions, you may find you are unable to give the next injection at the proper interval.
Table 3
Tenets for using long-acting IM risperidone for inpatients
| If the patient… | Then… |
|---|---|
| is receiving IM risperidone on admission and you decide to continue it | give the dose at the appropriate time if patient will not be discharged within 3 days of the injection appointment |
| is to be started on IM risperidone and to be discharged in <3 days | start treatment as an outpatient |
| is committed to the hospital for >3 weeks | start IM risperidone in the hospital |
| is admitted to be started on IM risperidone because starting as an outpatient has failed | start IM risperidone in the hospital |
Related resources
- Keith SJ, Pani L, Nick B, et al. Practical application of pharmacotherapy with long-acting risperidone for patients with schizophrenia. Psychiatr Serv. 2004;55(9):997-1005.
- Risperdal Consta. Risperidone long-acting injection. Janssen Pharmaceutica. Available at www.risperdalconsta.com. Accessed Feb. 25, 2005.
Drug brand names
- Fluphenazine • Prolixin
- Haloperidol • Haldol
- Risperidone (long-acting) • Risperdal Consta
Disclosure
Dr. Lauriello receives grant/research support from AstraZeneca Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly and Co. He is a consultant to or speaker for Eli Lilly and Co., Janssen Pharmaceutica, Pfizer Inc., and Bristol-Myers Squibb Co.
Dr. Keith is a consultant to or speaker for Bristol-Myers Squibb Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., and Pfizer Inc.
Knowing how to use IM risperidone—and other long-acting atypicals that are likely to be approved—will enable you to help your patients benefit from reliable antipsychotic dosing. Long-acting antipsychotics address the challenge that makes schizophrenia particularly difficult to treat: medication nonadherence because of psychotic illness’ effect on insight, reality testing, and motivation.1,2
Too few schizophrenia patients in the United States—perhaps <5% of appropriate candidates—receive depot antipsychotics.1 We believe these agents provide the best delivery system to our patients and welcome IM risperidone’s approval3
This article shares what we have learned from research and clinical practice about using injectable antipsychotics, with a focus on how to effectively use long-acting IM risperidone.
CONVENTIONAL ANTIPSYCHOTICS
Once seen as an improvement over oral conventional antipsychotics, IM agents were relegated over time to a means of coercion (as in, “If you don’t take your medicine orally, we’ll force you to take a shot.”). Oral atypical antipsychotics, with improved side-effect profiles and possibly reduced relapse risk, also discouraged psychiatrists from using long-acting conventional antipsychotics as first-line medication.4
Available agents. Fluphenazine and haloperidol—the two long-acting conventional antipsychotics available in the United States (Table 1)—are esterified to a fatty acid (oil) to create an IM injectable prodrug. They can be given in gluteal or deltoid injection, although doses >2 cc should be given in the gluteus.
Hydrolysis releases the active drug, usually within 3 days. This interval allows loading doses to reach therapeutic blood levels rapidly when the goal is to stabilize patients in the hospital or during a short-term crisis stay. Disadvantages include:
- pain and lasting reactions at the injection site
- risk of extrapyramidal symptoms (EPS), neuroleptic malignant syndrome, and tardive dyskinesia.5
Table 1
Administering long-acting injectable antipsychotics
| Name | Preparation | Dose range | Interval | Injection site | Comment |
|---|---|---|---|---|---|
| Fluphenazine | 25 mg/mL | 5 to 75 mg each injection | Every 1 to 2 weeks | Deltoid or gluteal | Site reaction common |
| Haloperidol | 50 or 100 mg/mL | 25 to 200 mg each injection | Every 2 to 4 weeks | Deltoid or gluteal | Site reaction common |
| Risperidone | 25, 37.5, or 50 mg in prefilled bottles | 25 to 50 mg each injection | Every 2 weeks | Gluteal only | Requires reconstitution, proprietary kit |
Depot administration. Fluphenazine depot is commonly given every 2 weeks, starting with 25 mg, but a weekly or monthly interval is not rare. The dose range is broad because the drug can be given in fine gradations from as low as 2.5 mg (0.1 cc) to 75 mg (3 cc). Thus, you can individually titrate it by varying the dose and/or interval.
Because haloperidol is usually given monthly and thus requires less-frequent dosing, it tends to be used more often than fluphenazine. Haloperidol can be given in shorter intervals but is rarely used at intervals >4 weeks. Usual dosing is 50 to 100 mg per shot but can range from small amounts to hundreds of milligrams.
Transition from oral to IM. Switching from an oral antipsychotic to a long-acting medication is straightforward. As long as test doses or history predetermine that patients have no untoward effects from fluphenazine or haloperidol, the first injection can be given and the oral agent maintained for 3 to 5 days.
Monitor for dystonias and other emergent EPS. Some practitioners pretreat with anticholinergics to avoid these neurologic side effects. If you can monitor the patient over the first week, you can often avoid pretreatment and add side-effect medication as needed.
LONG-ACTING IM RISPERIDONE
For technical and approval reasons, it took nearly a decade for a long-acting atypical to be developed and approved. Because risperidone could not easily be attached to an oil, the solution to making risperidone long-acting was to use microspheres.6
Microspheres are best conceptualized as a solid sphere of dissolvable suture-like material (glycolide-lactide polymers) embedded with risperidone bits. The microspheres are packaged dry and reconstituted at the clinic with aqueous diluent at the time of medication. Once reconstituted, it forms a suspension of microspheres in water.
‘Snow in a snow globe.’ Reconstituted long-acting risperidone appears like snow in a snow globe. With shaking, the microspheres become suspended but quickly settle in the bottle or syringe. Shake to resuspend the microspheres if you are giving an injection more than 2 minutes after the initial reconstitution. Reconstituted microspheres can be given up to 6 hours after hydration.
Transfer the medication to the syringe via the proprietary exchange system, and use the specialized needle to inject the medication into the gluteal region. Once injected, the microspheres swell with water from local muscle, then break down.
Delayed action. The microspheres begin releasing risperidone in 3 to 4 weeks. Therapeutic levels last approximately 2 weeks until the microspheres gradually convert to carbon dioxide and water. This delayed action requires coverage with oral or other depot medication. Coverage is no longer needed after the medication reaches a steady state (Figure).
Tolerability. As with any long-acting antipsychotic, establish riperidone’s tolerability by history or test dosing. No set number of doses will ensure that a patient won’t have an allergic reaction, but we usually recommend several days of oral dosing before the first injection.
Dosing interval. The approved dosing interval of every 2 weeks should work for most patients. Longer intervals are being studied but are not approved practice.
From oral to IM. Risperidone’s manufacturer recommends at least 3 weeks of coverage by another agent when transitioning from oral to IM to ensure that long-acting risperidone reaches a therapeutic level before being used alone.7 We use even longer coverage—4 to 6 weeks if feasible and acceptable to the patient. We worry more about under-medication than about possible overmedication caused by the overlap. We also consider other factors (Table 2).8
Knowing your patient’s history is critical to ensuring a safe transition. Imagine two patients who are stable on the same antipsychotic dose. When under-medicated during a dose switch, the first recedes into his room and is isolative, whereas the second hits his mother. The first patient will more likely tolerate a quick switch without untoward consequences; the second will need a longer and slower overlap to prevent a recurrence of violent behavior.
Figure Long-acting IM risperidone: Steady-state blood levels by 4th dose
Source: Adapted and reprinted with permission of Robert Lasser from a poster presented at the American Psychiatric Nurses Association annual meeting, Dallas, TX, 2002.Table 2
Switching from another antipsychotic to long-acting IM risperidone
|
DOSING IM RISPERIDONE
Choosing a dose of long-acting risperidone can be difficult. Several points of reference are helpful, but no formula exists. The long-acting form of any antipsychotic behaves differently from its oral counterpart. The maximum daily blood level is lower and the daily trough higher, so that blood levels are governed in a more narrow range. This allows fewer dose- or blood level-related side effects and steadier blood levels.
Dosing equivalents. Long-acting IM risperidone’s preclinical pharmacokinetics data suggested that 25 mg every 2 weeks is equivalent to 2 mg oral per day, 50 mg to 4 mg/d, and 75 mg to 6 mg/d.3 In clinical practice, we find equivalency is broader and represents a range of values. Thus, the 25-mg injection is equivalent to 2 to 4 mg of oral risperidone. Because oral risperidone’s average dose is slightly greater than 4 mg/d, the 25-mg injection should work for most patients.
Side effects. With IM risperidone, the maximum blood level is approximately 30% lower than with the oral dose, so dose-related EPS and prolactin elevation may be less than would be expected for the oral dose range.9 Individual sensitivities do exist, however. We have had some patients experience EPS at low doses and many others not experience EPS at high doses.
Recommendations. If evidence suggests that the patient might be stable on oral doses of 2 to 4 mg/d, start with the 25-mg, every 2-week injection. A recent study in which patients switched directly to long-acting risperidone, without intervening oral risperidone, supports this approach.10
Monitor the patient’s symptoms, being aware that the medication does not begin to take effect until 3 weeks after the first injection. That implies that the second injection is given before you know the efficacy of the first.
We try to maintain the patient on this regimen for several weeks, using oral supplementation if necessary and practical. If the patient requires supplementation throughout the four-injection, 2-month trial, we then:
- increase the dose to 37.5 mg
- repeat the 2-month trial with supplementation as necessary
- and, again, if the patient requires supplementation for the entire 2 months, increase to the 50-mg dose.
This plan requires patience by both clinician and patient but reduces overmedication.
SPECIAL CIRCUMSTANCES
Missed doses. Patients who are stable on a long-acting IM risperidone dose should be maintained indefinitely. As we have all experienced, however, indefinitely is rarely forever. Patients may need periodic dose adjustments or miss doses for a variety of reasons.
We find that patients who are up to a week overdue for an injection are still stable. When a patient arrives more than a week late, check for symptom worsening to determine if you need to supplement the injection with oral medication. If the patient has missed several months, you probably need to restart the initial process.
Inpatient use. Long-acting IM risperidone has been studied in hospitalized patients.11 Getting approval for inpatient use may be difficult, however, if inpatient services and the outpatient pharmacy are on separate budgets.
Though IM risperidone may not take effect until several weeks after a patient’s discharge, starting inpatient treatment may be appropriate. At our institution, we developed tenets for reviewing each case (Table 3).
Before we give any injection, we require that the system for outpatient injections—including place and payment source—be in place. Without these precautions, you may find you are unable to give the next injection at the proper interval.
Table 3
Tenets for using long-acting IM risperidone for inpatients
| If the patient… | Then… |
|---|---|
| is receiving IM risperidone on admission and you decide to continue it | give the dose at the appropriate time if patient will not be discharged within 3 days of the injection appointment |
| is to be started on IM risperidone and to be discharged in <3 days | start treatment as an outpatient |
| is committed to the hospital for >3 weeks | start IM risperidone in the hospital |
| is admitted to be started on IM risperidone because starting as an outpatient has failed | start IM risperidone in the hospital |
Related resources
- Keith SJ, Pani L, Nick B, et al. Practical application of pharmacotherapy with long-acting risperidone for patients with schizophrenia. Psychiatr Serv. 2004;55(9):997-1005.
- Risperdal Consta. Risperidone long-acting injection. Janssen Pharmaceutica. Available at www.risperdalconsta.com. Accessed Feb. 25, 2005.
Drug brand names
- Fluphenazine • Prolixin
- Haloperidol • Haldol
- Risperidone (long-acting) • Risperdal Consta
Disclosure
Dr. Lauriello receives grant/research support from AstraZeneca Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly and Co. He is a consultant to or speaker for Eli Lilly and Co., Janssen Pharmaceutica, Pfizer Inc., and Bristol-Myers Squibb Co.
Dr. Keith is a consultant to or speaker for Bristol-Myers Squibb Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., and Pfizer Inc.
1. Keith SJ, Kane JM. Partial compliance and patient consequences in schizophrenia: our patients can do better. J Clin Psychiatry 2003;64(11):1308-15.
2. Dolder CR, Lacro JP, Dunn LB, et al. Antipsychotic medication adherence: is there a difference between typical and atypical agents? Am J Psychiatry 2002;159(1):103-8.
3. Kane JM, Eerdekens M, Lindenmayer JP, et al. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry 2003;160(6):1125-32.
4. Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002;346(1):16-22.
5. Tandon R, Jibson MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry 2002;14(2):123-9.
6. Ramstack M, Grandolfi G, Mannaert E, et al. Long-acting risperidone: prolonged-release injectable delivery of risperidone using medisorb microsphere technology. Biol Psychiatry 2003;53(suppl 89):204.-
7. Janssen-Cilag Ltd. Product information for Risperdal Consta. Available at: http://www.janssencilag.co.uk (go to products page). Accessed February 3, 2005.
8. Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry 2003;64(10):1250-7.
9. Eerdekens M, Van Hove I, Remmerie B, Mannaert E. Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia. Schizophr Res 2004;70(1):91-100.
10. Lindenmayer JP, Eerdekens E, Berry SA, Eerdekens M. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J Clin Psychiatry 2004;65(8):1084-9.
11. Lauriello J, McEvoy JP, Rodriguez S, et al. Long-acting risperidone vs. placebo in the treatment of hospital inpatients with schizophrenia. Schizophr Res 2005;72(2-3):249-58.
1. Keith SJ, Kane JM. Partial compliance and patient consequences in schizophrenia: our patients can do better. J Clin Psychiatry 2003;64(11):1308-15.
2. Dolder CR, Lacro JP, Dunn LB, et al. Antipsychotic medication adherence: is there a difference between typical and atypical agents? Am J Psychiatry 2002;159(1):103-8.
3. Kane JM, Eerdekens M, Lindenmayer JP, et al. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry 2003;160(6):1125-32.
4. Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002;346(1):16-22.
5. Tandon R, Jibson MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry 2002;14(2):123-9.
6. Ramstack M, Grandolfi G, Mannaert E, et al. Long-acting risperidone: prolonged-release injectable delivery of risperidone using medisorb microsphere technology. Biol Psychiatry 2003;53(suppl 89):204.-
7. Janssen-Cilag Ltd. Product information for Risperdal Consta. Available at: http://www.janssencilag.co.uk (go to products page). Accessed February 3, 2005.
8. Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry 2003;64(10):1250-7.
9. Eerdekens M, Van Hove I, Remmerie B, Mannaert E. Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia. Schizophr Res 2004;70(1):91-100.
10. Lindenmayer JP, Eerdekens E, Berry SA, Eerdekens M. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J Clin Psychiatry 2004;65(8):1084-9.
11. Lauriello J, McEvoy JP, Rodriguez S, et al. Long-acting risperidone vs. placebo in the treatment of hospital inpatients with schizophrenia. Schizophr Res 2005;72(2-3):249-58.
What’s the best treatment for comorbid ADHD/bipolar mania?
Comorbid attention-deficit/hyperactivity disorder (ADHD) is nearly universal in youths with bipolar disorder (BPD),1 and comorbid mania has been noted in 16% of children with ADHD.2 Choosing medication for these complex patients is difficult because psychostimulants may worsen mania and mood stabilizers may not resolve ADHD symptoms. Yet, very little information exists on combining psychostimulants with mood stabilizers or atypical antipsychotics.
This article offers evidence to help you decide:
- which to treat first—ADHD or BPD
- how to individualize combination therapy.
CHALLENGES OF COMORBIDITY
Differential diagnosis. ADHD and bipolar disorder (BPD) symptoms overlap, and experts disagree on which symptoms indicate co-existing ADHD and BPD. Multiple daily mood swings and irritability are commonly found in prepubertal BPD.3 Recent reviews address differential diagnosis and specific assessment tools;3-5 after careful evaluation, then focus on treatment.
Treating comorbid ADHD and BPD usually requires more than one medication, and use of multiple drugs in children and adolescents is becoming increasingly common.6,7
PSYCHOSTIMULANTS AND MOOD STABILIZERS
Small, uncontrolled studies of children and adolescents with comorbid ADHD and BPD have shown that treatment with a mood stabilizer and a psychostimulant can control both sets of symptoms. For example:
- Lithium (serum levels 0.7 to 1.1 mEq/L) plus methylphenidate (10 to 20 mg/d) improved attention and hyperactivity symptoms more effectively than either agent alone in 7 children (6 boys, 1 girl) ages 6 to 10 hospitalized with disruptive behavioral disorders and BPD or major depression.8
- A retrospective analysis of 38 children (ages 3 to 16; 84% male) with BPD found that ADHD symptoms were 7.5 times more likely to improve if mood was stabilized before rather than after ADHD treatment with tricyclic antidepressants.9
The efficacy of combining a mood stabilizer and psychostimulant has been confirmed by only one controlled study—a randomized, placebo-controlled trial of mixed amphetamine salts in divalproex-treated patients.10 Forty patients (ages 6 to 17; 83% male) with BPD and ADHD received open-label divalproex (median dosage 750 mg/d) for 8 weeks. Thirty patients whose manic symptoms were significantly reduced entered a 4-week, double-blind, crossover trial of mixed amphetamine salts, 10 mg/d, or placebo.
Following this double-blind phase, 23 patients received open-label divalproex plus mixed amphetamine salts for 12 weeks. The Young Mania Rating Scale and Clinical Global Impression-Improvement scale were used to assess manic and ADHD symptoms during all three study phases.
Manic symptoms in patients treated with divalproex monotherapy improved significantly, but ADHD symptoms did not. ADHD symptoms improved more with divalproex plus mixed amphetamine salts than with divalproex plus placebo. One patient experienced manic symptom exacerbation with combination therapy.
PSYCHOSTIMULANTS AND ANTIPSYCHOTICS
Combinations of psychostimulants and atypical antipsychotics are commonly used in children and adolescents with comorbid psychiatric and behavioral disorders, such as ADHD and disruptive behavioral disorders (oppositional defiant disorder, conduct disorder). In 78 children ages 5 to 12 (83% male) with comorbid ADHD and a disruptive behavioral disorder, disruptive behavior and hyperactivity improved significantly with risperidone alone or with a psychostimulant.11
Combined psychostimulant/atypical antipsychotic therapy may help youths with comorbid ADHD and Tourette syndrome. Methylphenidate can reduce ADHD symptoms without exacerbating tics,12 and risperidone can treat tic disorders, even in patients with comorbid ADHD.13,14 No controlled trials have examined psychostimulant and atypical antipsychotic combinations in these patients, however.
Atypical antipsychotics have been shown to be effective in treating adult BPD, and limited data suggest the same to be true in pediatric patients. Olanzapine, quetiapine, and risperidone have been shown to reduce manic symptoms in children and adolescents (Table 1).15-17 Atypical antipsychotics, however, have been associated with metabolic side effects, including weight gain, hyperglycemia, hyperlipidemia, and hyperprolactinemia.
To date, no study has systematically evaluated combination psychostimulant and atypical antipsychotic treatment in comorbid ADHD and BPD. In the olanzapine and risperidone studies,15,17 concomitant psychostimulant use was permitted and did not affect manic symptom response.
Table 1
Atypical antipsychotic studies in pediatric bipolar disorder
| Drug and mean dosage | Study design | Sample characteristics | Efficacy measures | Results |
|---|---|---|---|---|
| Olanzapine15 9.6±4.3 mg/d | 8-week, open-label monotherapy | 23 patients, mean age 10±3 yrs, 57% male | ≥30% decrease on YMRS | Response rate 61% |
| Quetiapine16 432 mg/d | 6-week, randomized, placebo-controlled, adjunctive (+DVP) | 30 patients, mean age 14±2 yrs, 53% male | ≥50% decrease on YMRS | Response rates: DVP + placebo 53% DVP + quetiapine 87% |
| Risperidone17 1.7±1.3 mg/d | Retrospective, adjunctive | 28 patients, mean age 10±4 yrs, 97% male | ≤2 on CGI-I | Response rate 82% |
| CGI-I: Clinical Global Impressions-Improvement scale | ||||
| DVP: divalproex | ||||
| YMRS: Young Mania Rating Scale | ||||
WHICH COMBINATION?
Which combination treatment—psychostimulant plus mood stabilizer, psychostimulant plus atypical antipsychotic, or psychostimulant plus both mood stabilizer and atypical antipsychotic—is most appropriate for a child or adolescent with comorbid ADHD and BPD? Recommended treatment strategies are based on studies of pediatric and adult BPD and expert consensus.18,19
Consider the type of bipolar episode (Table 2).
For initial treatment of youths with BPD manic or mixed without psychosis, recent guidelines by Kowatch et al suggest using mood-stabilizer or atypical antipsychotic monotherapy. Youths who are more severely ill or present with psychosis may respond more favorably to a mood stabilizer plus an atypical antipsychotic.16,19
Individual patient traits will also determine whether a mood stabilizer or atypical antipsychotic is used and which agent within either medication class is chosen. For example:
- If the patient is aggressive, risperidone may reduce aggression and manic symptoms. Among the atypicals, risperidone has the most evidence suggesting efficacy for aggressive behaviors in youths across psychiatric conditions.20
- If an atypical antipsychotic is warranted and the patient’s weight is an issue, ziprasidone or aripiprazole would be preferred. These agents are considered weight-neutral compared with other atypicals.20
Other factors to consider include medication side effects, interactions, adherence, and cost.
Table 2
Mood stabilizer, atypical antipsychotic, or both with ADHD therapy?
| Type of bipolar episode | Recommended psychotropics |
|---|---|
| Manic or mixed episode with psychosis | Mood stabilizer + atypical antipsychotic |
| Manic or mixed episode without psychosis | Mood stabilizer or atypical antipsychotic monotherapy first
|
| Prominent irritability without psychosis | Atypical antipsychotic |
| Source: Adapted from references 18 and 19 | |
WHICH TO TREAT FIRST?
If the child or adolescent with comorbid ADHD and BPD has acute manic symptoms, available data and expert opinion recommend starting treatment with a mood stabilizer or atypical antipsychotic.9,19,21 If ADHD symptoms persist after mood stabilization, a psychostimulant trial is warranted.
In practice, however, youngsters usually present with ADHD symptoms first. Psychostimulant treatment is initiated, ADHD symptoms are controlled, and the child’s academic and social functioning improve. Bipolar symptoms emerge later, often heralded by a depressive or mixed episode. Is it necessary to discontinue the psychostimulant and risk worsening ADHD symptoms before starting a mood stabilizer or atypical antipsychotic?
Clinical lore and one case report suggest that psychostimulants may destabilize mood.22,23 A 10-year-old boy with severe hyperactivity and family history of BPD experienced manic symptoms—rapid and pressured speech, grandiose delusions of identity, and tangentiality of thought processes—during methylphenidate treatment.22
Conversely, an analysis24 of children ages 7 to 10 from the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD contradicts these assumptions. Although a clinical diagnosis of BPD was not assigned, 29 children (83% male) met the Diagnostic Interview Schedule for Children proxy for mania, 32 (88% male) met the Child Behavior Checklist proxy, and 7 met both proxies for mania.
The first month of methylphenidate treatment did not increase irritability, mood symptoms, or mania in the 54 children with ADHD and manic symptoms, compared with children with ADHD alone. The authors concluded that clinicians should not categorically avoid using stimulants in children with ADHD and some manic symptoms.
In a study by Pavuluri et al18 of pediatric bipolar type I disorder, 17 patients (mean age 11±4 years) received mood stabilizers—following a drug therapy algorithm that included risperidone—and typically received a psychostimulant after mood stabilization. This group was compared with 17 patients receiving “treatment as usual.”
The usual-treatment group remained on psychostimulant therapy after BPD intervention with a mood stabilizer and was less likely to receive an atypical antipsychotic. The algorithm treatment group showed better outcomes overall, specifically for mania and aggression.
Clearly, more studies are needed to determine the optimum treatment sequence with psychostimulants and mood stabilizers in youths with comorbid ADHD and BPD. With either approach, routinely monitor patients treated with psychostimulants for emerging or worsening bipolar symptoms.
LESSONS FROM CLINICAL EXPERIENCE
Nonstimulants. Using psychostimulants is appropriate for ADHD in patients with stable bipolar symptoms. Evidence for using nonstimulants such as clonidine, guanfacine, or atomoxetine is less clear.
In a naturalistic study of 153 children and adolescent outpatients treated with atomoxetine, 51 (33%) experienced irritability, aggression, mania, or hypomania. Of these patients, 31 (61%) had a family history of a mood disorder, and 41 (80%) had a personal history of mood symptoms.25 Although these findings suggest that atomoxetine may be associated with mood exacerbation and hypomania, additional data are needed to determine whether atomoxetine may be used for ADHD symptoms in youths with comorbid BPD.
Atypical antipsychotics. Mood stabilization—particularly with atypical antipsychotics—often can address comorbid disruptive behaviors and aggressive symptoms. Combinations of atypical antipsychotics with psychostimulants are largely devoid of drug-drug interactions and metabolic interference, making them uncomplicated to use.
Though published studies of pediatric BPD have focused on three atypical antipsychotics—olanzapine, quetiapine, and risperidone—any agent in this class can be used in this population, with the choice often depending on how side effects are likely to affect individual patients (Table 3 ).
Pharmacologic attributes may also determine which atypical antipsychotic is used. For example, ziprasidone’s serotonergic profile—with serotonin-1A receptor agonism and serotonin-1D antagonism—may make it useful for patients with mixed states and bipolar depression.26 Aripiprazole offers potential synergism of dopamine agonism with psychostimulant therapy, which could be useful for treating both disruptive behaviors and ADHD.
Table 3
Using atypical antipsychotics to treat comorbid ADHD/bipolar disorder
| Drug | Target dosage (mg/d) | Side effects | Useful in… |
|---|---|---|---|
| Aripiprazole | 10 to 15 | Nausea, vomiting | Comorbid disruptive behavioral disorders, maintenance stabilization |
| Olanzapine | 10 to 20 | Weight gain, hyperlipidemia, hyperglycemia, sedation | Maintenance stabilization |
| Quetiapine | 400 to 600 | Weight gain, sedation | Mixed states, bipolar depression |
| Risperidone | 1 to 2 | Weight gain, hyperprolactinemia, extrapyramidal symptoms | Comorbid disruptive behavioral disorders, including aggression |
| Ziprasidone | 80 to 120 | Cardiac abnormalities, akathisia | Mixed states, bipolar depression |
Related resources
- Child and Adolescent Bipolar Foundation. www.bpkids.org
- Children and Adults with Attention-Deficit Hyperactivity Disorder (CHADD). www.chadd.org
- Findling RF, Kowatch RA, Post RM. P ediatric bipolar disorders: a handbook for clinicians. London: Martin Dunitz Press, 2002.
Drug brand names
- Atomoxetine • Strattera
- Aripiprazole • Abilify
- Divalproex • Depakote
- Olanzapine • Zyprexa
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Ziprasidone • Geodon
Disclosures
Dr. Patel is a consultant to Eli Lilly and Co. and a speaker for Eli Lilly and Co. and Pfizer Inc.
Dr. Sallee receives research support from Otsuka America Pharmaceutical, Pfizer Inc., and Bristol-Myers Squibb Co. and is a consultant or speaker for Eli Lilly and Co, Otsuka America Pharmaceutical, and Pfizer Inc.
1. Geller B, Cooper TB, Sun K, et al. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry 1998;37(2):171-8.
2. Wozniak J, Biederman J, Kiely K, et al. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry 1995;34(7):867-76.
3. Kowatch RA, DelBello MP. Pediatric bipolar disorder: mood swings, irritability are diagnostic cues. Current Psychiatry 2003;2(3):40-7.
4. Quinn CA, Fristad MA. Defining and identifying early onset bipolar spectrum disorder. Curr Psychiatry Rep 2004;6(2):101-7.
5. Bhatara VS, Feil M, Hoagwood K, et al. Trends in combined pharmacotherapy with stimulants for children. Psychiatr Serv 2002;53(3):244.-
6. Zito JM, Safer DJ, dosReis S, et al. Psychotherapeutic medication patterns for youths with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 1999;153(12):1257-63.
7. Wolf DV, Wagner KD. Bipolar disorder in children and adolescents. CNS Spectr 2003;8(12):954-9.
8. Carlson GA, Rapport MD, Kelly KL, Pataki CS. The effects of methylphenidate and lithium on attention and activity level. J Am Acad Child Adolesc Psychiatry 1992;31(2):262-70.
9. Biederman J, Mick E, Prince J, et al. Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder. J Child Adolesc Psychopharmacol 1999;9(4):247-56.
10. Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry 2005;162(1):58-64.
11. Aman MG, Binder C, Turgay A. Risperidone effects in the presence/absence of psychostimulant medicine in children with ADHD, other disruptive behavioral disorders, and subaverage IQ. J Child Adolesc Psychopharmacology 2004;14(2):243-54.
12. Gadow KD, Sverd J, Sprafkin J, et al. Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder. Arch Gen Psychiatry 1999;56(4):330-6.
13. Gaffney GR, Perry PJ, Lund BC, et al. Risperidone versus clonidine in the treatment of children and adolescents with Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry 2002;41(3):330-6.
14. Lombroso PJ, Scahill L, King RA, et al. Risperidone treatment of children and adolescents with chronic tic disorders: a preliminary report. J Am Acad Child Adolesc Psychiatry 1995;34(9):1147-52.
15. Frazier JA, Biederman J, Tohen M, et al. A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol 2001;11(3):239-50.
16. DelBello MP, Schwiers ML, Rosenberg HL, Strakowski SM. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry 2002;41(10):1216-23.
17. Frazier JA, Meyer MC, Biederman J, et al. Risperidone treatment for juvenile bipolar disorder: a retrospective chart review. J Am Acad Child Adolesc Psychiatry 1999;38(8):960-5.
18. Pavuluri MN, Henry DB, Devineni B, et al. A pharmacotherapy algorithm for stabilization and maintenance of pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry 2004;43(7):859-67.
19. Kowatch RA, Fristad M, Birmaher B, et al. Treatment guidelines for children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005;44(3):213-35.
20. Findling RL, McNamara NK. Atypical antipsychotics in the treatment of children and adolescents: clinical applications. J Clin Psychiatry 2004;65(suppl 6):30-44.
21. Kowatch RA, Sethuraman G, Hume JH, et al. Combination pharmacotherapy in children and adolescents with bipolar disorder. Biol Psychiatry 2003;53(11):978-84.
22. Koehler-Troy C, Strober M, Malenbaum R. Methylphenidate-induced mania in a prepubertal child. J Clin Psychiatry 1986;47(11):566-7.
23. Craney J, Geller B. Clinical implications of antidepressant and stimulant use on switching from depression to mania in children. J Child Adolesc Psychopharmacol 2003;13(2):201-4.
24. Galanter CA, Carlson GA, Jensen PS, et al. Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial. J Child Adolesc Psychopharmacol 2003;13(2):123-36.
25. Henderson TA, Hartman K. Aggression, mania, and hypomania induction associated with atomoxetine. Pediatrics 2004;114(3):895-6.
26. Sallee FR, Gilbert DL, Vinks AA, et al. Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission. J Am Acad Child Adolesc Psychiatry 2003;42(8):902-7.
Comorbid attention-deficit/hyperactivity disorder (ADHD) is nearly universal in youths with bipolar disorder (BPD),1 and comorbid mania has been noted in 16% of children with ADHD.2 Choosing medication for these complex patients is difficult because psychostimulants may worsen mania and mood stabilizers may not resolve ADHD symptoms. Yet, very little information exists on combining psychostimulants with mood stabilizers or atypical antipsychotics.
This article offers evidence to help you decide:
- which to treat first—ADHD or BPD
- how to individualize combination therapy.
CHALLENGES OF COMORBIDITY
Differential diagnosis. ADHD and bipolar disorder (BPD) symptoms overlap, and experts disagree on which symptoms indicate co-existing ADHD and BPD. Multiple daily mood swings and irritability are commonly found in prepubertal BPD.3 Recent reviews address differential diagnosis and specific assessment tools;3-5 after careful evaluation, then focus on treatment.
Treating comorbid ADHD and BPD usually requires more than one medication, and use of multiple drugs in children and adolescents is becoming increasingly common.6,7
PSYCHOSTIMULANTS AND MOOD STABILIZERS
Small, uncontrolled studies of children and adolescents with comorbid ADHD and BPD have shown that treatment with a mood stabilizer and a psychostimulant can control both sets of symptoms. For example:
- Lithium (serum levels 0.7 to 1.1 mEq/L) plus methylphenidate (10 to 20 mg/d) improved attention and hyperactivity symptoms more effectively than either agent alone in 7 children (6 boys, 1 girl) ages 6 to 10 hospitalized with disruptive behavioral disorders and BPD or major depression.8
- A retrospective analysis of 38 children (ages 3 to 16; 84% male) with BPD found that ADHD symptoms were 7.5 times more likely to improve if mood was stabilized before rather than after ADHD treatment with tricyclic antidepressants.9
The efficacy of combining a mood stabilizer and psychostimulant has been confirmed by only one controlled study—a randomized, placebo-controlled trial of mixed amphetamine salts in divalproex-treated patients.10 Forty patients (ages 6 to 17; 83% male) with BPD and ADHD received open-label divalproex (median dosage 750 mg/d) for 8 weeks. Thirty patients whose manic symptoms were significantly reduced entered a 4-week, double-blind, crossover trial of mixed amphetamine salts, 10 mg/d, or placebo.
Following this double-blind phase, 23 patients received open-label divalproex plus mixed amphetamine salts for 12 weeks. The Young Mania Rating Scale and Clinical Global Impression-Improvement scale were used to assess manic and ADHD symptoms during all three study phases.
Manic symptoms in patients treated with divalproex monotherapy improved significantly, but ADHD symptoms did not. ADHD symptoms improved more with divalproex plus mixed amphetamine salts than with divalproex plus placebo. One patient experienced manic symptom exacerbation with combination therapy.
PSYCHOSTIMULANTS AND ANTIPSYCHOTICS
Combinations of psychostimulants and atypical antipsychotics are commonly used in children and adolescents with comorbid psychiatric and behavioral disorders, such as ADHD and disruptive behavioral disorders (oppositional defiant disorder, conduct disorder). In 78 children ages 5 to 12 (83% male) with comorbid ADHD and a disruptive behavioral disorder, disruptive behavior and hyperactivity improved significantly with risperidone alone or with a psychostimulant.11
Combined psychostimulant/atypical antipsychotic therapy may help youths with comorbid ADHD and Tourette syndrome. Methylphenidate can reduce ADHD symptoms without exacerbating tics,12 and risperidone can treat tic disorders, even in patients with comorbid ADHD.13,14 No controlled trials have examined psychostimulant and atypical antipsychotic combinations in these patients, however.
Atypical antipsychotics have been shown to be effective in treating adult BPD, and limited data suggest the same to be true in pediatric patients. Olanzapine, quetiapine, and risperidone have been shown to reduce manic symptoms in children and adolescents (Table 1).15-17 Atypical antipsychotics, however, have been associated with metabolic side effects, including weight gain, hyperglycemia, hyperlipidemia, and hyperprolactinemia.
To date, no study has systematically evaluated combination psychostimulant and atypical antipsychotic treatment in comorbid ADHD and BPD. In the olanzapine and risperidone studies,15,17 concomitant psychostimulant use was permitted and did not affect manic symptom response.
Table 1
Atypical antipsychotic studies in pediatric bipolar disorder
| Drug and mean dosage | Study design | Sample characteristics | Efficacy measures | Results |
|---|---|---|---|---|
| Olanzapine15 9.6±4.3 mg/d | 8-week, open-label monotherapy | 23 patients, mean age 10±3 yrs, 57% male | ≥30% decrease on YMRS | Response rate 61% |
| Quetiapine16 432 mg/d | 6-week, randomized, placebo-controlled, adjunctive (+DVP) | 30 patients, mean age 14±2 yrs, 53% male | ≥50% decrease on YMRS | Response rates: DVP + placebo 53% DVP + quetiapine 87% |
| Risperidone17 1.7±1.3 mg/d | Retrospective, adjunctive | 28 patients, mean age 10±4 yrs, 97% male | ≤2 on CGI-I | Response rate 82% |
| CGI-I: Clinical Global Impressions-Improvement scale | ||||
| DVP: divalproex | ||||
| YMRS: Young Mania Rating Scale | ||||
WHICH COMBINATION?
Which combination treatment—psychostimulant plus mood stabilizer, psychostimulant plus atypical antipsychotic, or psychostimulant plus both mood stabilizer and atypical antipsychotic—is most appropriate for a child or adolescent with comorbid ADHD and BPD? Recommended treatment strategies are based on studies of pediatric and adult BPD and expert consensus.18,19
Consider the type of bipolar episode (Table 2).
For initial treatment of youths with BPD manic or mixed without psychosis, recent guidelines by Kowatch et al suggest using mood-stabilizer or atypical antipsychotic monotherapy. Youths who are more severely ill or present with psychosis may respond more favorably to a mood stabilizer plus an atypical antipsychotic.16,19
Individual patient traits will also determine whether a mood stabilizer or atypical antipsychotic is used and which agent within either medication class is chosen. For example:
- If the patient is aggressive, risperidone may reduce aggression and manic symptoms. Among the atypicals, risperidone has the most evidence suggesting efficacy for aggressive behaviors in youths across psychiatric conditions.20
- If an atypical antipsychotic is warranted and the patient’s weight is an issue, ziprasidone or aripiprazole would be preferred. These agents are considered weight-neutral compared with other atypicals.20
Other factors to consider include medication side effects, interactions, adherence, and cost.
Table 2
Mood stabilizer, atypical antipsychotic, or both with ADHD therapy?
| Type of bipolar episode | Recommended psychotropics |
|---|---|
| Manic or mixed episode with psychosis | Mood stabilizer + atypical antipsychotic |
| Manic or mixed episode without psychosis | Mood stabilizer or atypical antipsychotic monotherapy first
|
| Prominent irritability without psychosis | Atypical antipsychotic |
| Source: Adapted from references 18 and 19 | |
WHICH TO TREAT FIRST?
If the child or adolescent with comorbid ADHD and BPD has acute manic symptoms, available data and expert opinion recommend starting treatment with a mood stabilizer or atypical antipsychotic.9,19,21 If ADHD symptoms persist after mood stabilization, a psychostimulant trial is warranted.
In practice, however, youngsters usually present with ADHD symptoms first. Psychostimulant treatment is initiated, ADHD symptoms are controlled, and the child’s academic and social functioning improve. Bipolar symptoms emerge later, often heralded by a depressive or mixed episode. Is it necessary to discontinue the psychostimulant and risk worsening ADHD symptoms before starting a mood stabilizer or atypical antipsychotic?
Clinical lore and one case report suggest that psychostimulants may destabilize mood.22,23 A 10-year-old boy with severe hyperactivity and family history of BPD experienced manic symptoms—rapid and pressured speech, grandiose delusions of identity, and tangentiality of thought processes—during methylphenidate treatment.22
Conversely, an analysis24 of children ages 7 to 10 from the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD contradicts these assumptions. Although a clinical diagnosis of BPD was not assigned, 29 children (83% male) met the Diagnostic Interview Schedule for Children proxy for mania, 32 (88% male) met the Child Behavior Checklist proxy, and 7 met both proxies for mania.
The first month of methylphenidate treatment did not increase irritability, mood symptoms, or mania in the 54 children with ADHD and manic symptoms, compared with children with ADHD alone. The authors concluded that clinicians should not categorically avoid using stimulants in children with ADHD and some manic symptoms.
In a study by Pavuluri et al18 of pediatric bipolar type I disorder, 17 patients (mean age 11±4 years) received mood stabilizers—following a drug therapy algorithm that included risperidone—and typically received a psychostimulant after mood stabilization. This group was compared with 17 patients receiving “treatment as usual.”
The usual-treatment group remained on psychostimulant therapy after BPD intervention with a mood stabilizer and was less likely to receive an atypical antipsychotic. The algorithm treatment group showed better outcomes overall, specifically for mania and aggression.
Clearly, more studies are needed to determine the optimum treatment sequence with psychostimulants and mood stabilizers in youths with comorbid ADHD and BPD. With either approach, routinely monitor patients treated with psychostimulants for emerging or worsening bipolar symptoms.
LESSONS FROM CLINICAL EXPERIENCE
Nonstimulants. Using psychostimulants is appropriate for ADHD in patients with stable bipolar symptoms. Evidence for using nonstimulants such as clonidine, guanfacine, or atomoxetine is less clear.
In a naturalistic study of 153 children and adolescent outpatients treated with atomoxetine, 51 (33%) experienced irritability, aggression, mania, or hypomania. Of these patients, 31 (61%) had a family history of a mood disorder, and 41 (80%) had a personal history of mood symptoms.25 Although these findings suggest that atomoxetine may be associated with mood exacerbation and hypomania, additional data are needed to determine whether atomoxetine may be used for ADHD symptoms in youths with comorbid BPD.
Atypical antipsychotics. Mood stabilization—particularly with atypical antipsychotics—often can address comorbid disruptive behaviors and aggressive symptoms. Combinations of atypical antipsychotics with psychostimulants are largely devoid of drug-drug interactions and metabolic interference, making them uncomplicated to use.
Though published studies of pediatric BPD have focused on three atypical antipsychotics—olanzapine, quetiapine, and risperidone—any agent in this class can be used in this population, with the choice often depending on how side effects are likely to affect individual patients (Table 3 ).
Pharmacologic attributes may also determine which atypical antipsychotic is used. For example, ziprasidone’s serotonergic profile—with serotonin-1A receptor agonism and serotonin-1D antagonism—may make it useful for patients with mixed states and bipolar depression.26 Aripiprazole offers potential synergism of dopamine agonism with psychostimulant therapy, which could be useful for treating both disruptive behaviors and ADHD.
Table 3
Using atypical antipsychotics to treat comorbid ADHD/bipolar disorder
| Drug | Target dosage (mg/d) | Side effects | Useful in… |
|---|---|---|---|
| Aripiprazole | 10 to 15 | Nausea, vomiting | Comorbid disruptive behavioral disorders, maintenance stabilization |
| Olanzapine | 10 to 20 | Weight gain, hyperlipidemia, hyperglycemia, sedation | Maintenance stabilization |
| Quetiapine | 400 to 600 | Weight gain, sedation | Mixed states, bipolar depression |
| Risperidone | 1 to 2 | Weight gain, hyperprolactinemia, extrapyramidal symptoms | Comorbid disruptive behavioral disorders, including aggression |
| Ziprasidone | 80 to 120 | Cardiac abnormalities, akathisia | Mixed states, bipolar depression |
Related resources
- Child and Adolescent Bipolar Foundation. www.bpkids.org
- Children and Adults with Attention-Deficit Hyperactivity Disorder (CHADD). www.chadd.org
- Findling RF, Kowatch RA, Post RM. P ediatric bipolar disorders: a handbook for clinicians. London: Martin Dunitz Press, 2002.
Drug brand names
- Atomoxetine • Strattera
- Aripiprazole • Abilify
- Divalproex • Depakote
- Olanzapine • Zyprexa
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Ziprasidone • Geodon
Disclosures
Dr. Patel is a consultant to Eli Lilly and Co. and a speaker for Eli Lilly and Co. and Pfizer Inc.
Dr. Sallee receives research support from Otsuka America Pharmaceutical, Pfizer Inc., and Bristol-Myers Squibb Co. and is a consultant or speaker for Eli Lilly and Co, Otsuka America Pharmaceutical, and Pfizer Inc.
Comorbid attention-deficit/hyperactivity disorder (ADHD) is nearly universal in youths with bipolar disorder (BPD),1 and comorbid mania has been noted in 16% of children with ADHD.2 Choosing medication for these complex patients is difficult because psychostimulants may worsen mania and mood stabilizers may not resolve ADHD symptoms. Yet, very little information exists on combining psychostimulants with mood stabilizers or atypical antipsychotics.
This article offers evidence to help you decide:
- which to treat first—ADHD or BPD
- how to individualize combination therapy.
CHALLENGES OF COMORBIDITY
Differential diagnosis. ADHD and bipolar disorder (BPD) symptoms overlap, and experts disagree on which symptoms indicate co-existing ADHD and BPD. Multiple daily mood swings and irritability are commonly found in prepubertal BPD.3 Recent reviews address differential diagnosis and specific assessment tools;3-5 after careful evaluation, then focus on treatment.
Treating comorbid ADHD and BPD usually requires more than one medication, and use of multiple drugs in children and adolescents is becoming increasingly common.6,7
PSYCHOSTIMULANTS AND MOOD STABILIZERS
Small, uncontrolled studies of children and adolescents with comorbid ADHD and BPD have shown that treatment with a mood stabilizer and a psychostimulant can control both sets of symptoms. For example:
- Lithium (serum levels 0.7 to 1.1 mEq/L) plus methylphenidate (10 to 20 mg/d) improved attention and hyperactivity symptoms more effectively than either agent alone in 7 children (6 boys, 1 girl) ages 6 to 10 hospitalized with disruptive behavioral disorders and BPD or major depression.8
- A retrospective analysis of 38 children (ages 3 to 16; 84% male) with BPD found that ADHD symptoms were 7.5 times more likely to improve if mood was stabilized before rather than after ADHD treatment with tricyclic antidepressants.9
The efficacy of combining a mood stabilizer and psychostimulant has been confirmed by only one controlled study—a randomized, placebo-controlled trial of mixed amphetamine salts in divalproex-treated patients.10 Forty patients (ages 6 to 17; 83% male) with BPD and ADHD received open-label divalproex (median dosage 750 mg/d) for 8 weeks. Thirty patients whose manic symptoms were significantly reduced entered a 4-week, double-blind, crossover trial of mixed amphetamine salts, 10 mg/d, or placebo.
Following this double-blind phase, 23 patients received open-label divalproex plus mixed amphetamine salts for 12 weeks. The Young Mania Rating Scale and Clinical Global Impression-Improvement scale were used to assess manic and ADHD symptoms during all three study phases.
Manic symptoms in patients treated with divalproex monotherapy improved significantly, but ADHD symptoms did not. ADHD symptoms improved more with divalproex plus mixed amphetamine salts than with divalproex plus placebo. One patient experienced manic symptom exacerbation with combination therapy.
PSYCHOSTIMULANTS AND ANTIPSYCHOTICS
Combinations of psychostimulants and atypical antipsychotics are commonly used in children and adolescents with comorbid psychiatric and behavioral disorders, such as ADHD and disruptive behavioral disorders (oppositional defiant disorder, conduct disorder). In 78 children ages 5 to 12 (83% male) with comorbid ADHD and a disruptive behavioral disorder, disruptive behavior and hyperactivity improved significantly with risperidone alone or with a psychostimulant.11
Combined psychostimulant/atypical antipsychotic therapy may help youths with comorbid ADHD and Tourette syndrome. Methylphenidate can reduce ADHD symptoms without exacerbating tics,12 and risperidone can treat tic disorders, even in patients with comorbid ADHD.13,14 No controlled trials have examined psychostimulant and atypical antipsychotic combinations in these patients, however.
Atypical antipsychotics have been shown to be effective in treating adult BPD, and limited data suggest the same to be true in pediatric patients. Olanzapine, quetiapine, and risperidone have been shown to reduce manic symptoms in children and adolescents (Table 1).15-17 Atypical antipsychotics, however, have been associated with metabolic side effects, including weight gain, hyperglycemia, hyperlipidemia, and hyperprolactinemia.
To date, no study has systematically evaluated combination psychostimulant and atypical antipsychotic treatment in comorbid ADHD and BPD. In the olanzapine and risperidone studies,15,17 concomitant psychostimulant use was permitted and did not affect manic symptom response.
Table 1
Atypical antipsychotic studies in pediatric bipolar disorder
| Drug and mean dosage | Study design | Sample characteristics | Efficacy measures | Results |
|---|---|---|---|---|
| Olanzapine15 9.6±4.3 mg/d | 8-week, open-label monotherapy | 23 patients, mean age 10±3 yrs, 57% male | ≥30% decrease on YMRS | Response rate 61% |
| Quetiapine16 432 mg/d | 6-week, randomized, placebo-controlled, adjunctive (+DVP) | 30 patients, mean age 14±2 yrs, 53% male | ≥50% decrease on YMRS | Response rates: DVP + placebo 53% DVP + quetiapine 87% |
| Risperidone17 1.7±1.3 mg/d | Retrospective, adjunctive | 28 patients, mean age 10±4 yrs, 97% male | ≤2 on CGI-I | Response rate 82% |
| CGI-I: Clinical Global Impressions-Improvement scale | ||||
| DVP: divalproex | ||||
| YMRS: Young Mania Rating Scale | ||||
WHICH COMBINATION?
Which combination treatment—psychostimulant plus mood stabilizer, psychostimulant plus atypical antipsychotic, or psychostimulant plus both mood stabilizer and atypical antipsychotic—is most appropriate for a child or adolescent with comorbid ADHD and BPD? Recommended treatment strategies are based on studies of pediatric and adult BPD and expert consensus.18,19
Consider the type of bipolar episode (Table 2).
For initial treatment of youths with BPD manic or mixed without psychosis, recent guidelines by Kowatch et al suggest using mood-stabilizer or atypical antipsychotic monotherapy. Youths who are more severely ill or present with psychosis may respond more favorably to a mood stabilizer plus an atypical antipsychotic.16,19
Individual patient traits will also determine whether a mood stabilizer or atypical antipsychotic is used and which agent within either medication class is chosen. For example:
- If the patient is aggressive, risperidone may reduce aggression and manic symptoms. Among the atypicals, risperidone has the most evidence suggesting efficacy for aggressive behaviors in youths across psychiatric conditions.20
- If an atypical antipsychotic is warranted and the patient’s weight is an issue, ziprasidone or aripiprazole would be preferred. These agents are considered weight-neutral compared with other atypicals.20
Other factors to consider include medication side effects, interactions, adherence, and cost.
Table 2
Mood stabilizer, atypical antipsychotic, or both with ADHD therapy?
| Type of bipolar episode | Recommended psychotropics |
|---|---|
| Manic or mixed episode with psychosis | Mood stabilizer + atypical antipsychotic |
| Manic or mixed episode without psychosis | Mood stabilizer or atypical antipsychotic monotherapy first
|
| Prominent irritability without psychosis | Atypical antipsychotic |
| Source: Adapted from references 18 and 19 | |
WHICH TO TREAT FIRST?
If the child or adolescent with comorbid ADHD and BPD has acute manic symptoms, available data and expert opinion recommend starting treatment with a mood stabilizer or atypical antipsychotic.9,19,21 If ADHD symptoms persist after mood stabilization, a psychostimulant trial is warranted.
In practice, however, youngsters usually present with ADHD symptoms first. Psychostimulant treatment is initiated, ADHD symptoms are controlled, and the child’s academic and social functioning improve. Bipolar symptoms emerge later, often heralded by a depressive or mixed episode. Is it necessary to discontinue the psychostimulant and risk worsening ADHD symptoms before starting a mood stabilizer or atypical antipsychotic?
Clinical lore and one case report suggest that psychostimulants may destabilize mood.22,23 A 10-year-old boy with severe hyperactivity and family history of BPD experienced manic symptoms—rapid and pressured speech, grandiose delusions of identity, and tangentiality of thought processes—during methylphenidate treatment.22
Conversely, an analysis24 of children ages 7 to 10 from the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD contradicts these assumptions. Although a clinical diagnosis of BPD was not assigned, 29 children (83% male) met the Diagnostic Interview Schedule for Children proxy for mania, 32 (88% male) met the Child Behavior Checklist proxy, and 7 met both proxies for mania.
The first month of methylphenidate treatment did not increase irritability, mood symptoms, or mania in the 54 children with ADHD and manic symptoms, compared with children with ADHD alone. The authors concluded that clinicians should not categorically avoid using stimulants in children with ADHD and some manic symptoms.
In a study by Pavuluri et al18 of pediatric bipolar type I disorder, 17 patients (mean age 11±4 years) received mood stabilizers—following a drug therapy algorithm that included risperidone—and typically received a psychostimulant after mood stabilization. This group was compared with 17 patients receiving “treatment as usual.”
The usual-treatment group remained on psychostimulant therapy after BPD intervention with a mood stabilizer and was less likely to receive an atypical antipsychotic. The algorithm treatment group showed better outcomes overall, specifically for mania and aggression.
Clearly, more studies are needed to determine the optimum treatment sequence with psychostimulants and mood stabilizers in youths with comorbid ADHD and BPD. With either approach, routinely monitor patients treated with psychostimulants for emerging or worsening bipolar symptoms.
LESSONS FROM CLINICAL EXPERIENCE
Nonstimulants. Using psychostimulants is appropriate for ADHD in patients with stable bipolar symptoms. Evidence for using nonstimulants such as clonidine, guanfacine, or atomoxetine is less clear.
In a naturalistic study of 153 children and adolescent outpatients treated with atomoxetine, 51 (33%) experienced irritability, aggression, mania, or hypomania. Of these patients, 31 (61%) had a family history of a mood disorder, and 41 (80%) had a personal history of mood symptoms.25 Although these findings suggest that atomoxetine may be associated with mood exacerbation and hypomania, additional data are needed to determine whether atomoxetine may be used for ADHD symptoms in youths with comorbid BPD.
Atypical antipsychotics. Mood stabilization—particularly with atypical antipsychotics—often can address comorbid disruptive behaviors and aggressive symptoms. Combinations of atypical antipsychotics with psychostimulants are largely devoid of drug-drug interactions and metabolic interference, making them uncomplicated to use.
Though published studies of pediatric BPD have focused on three atypical antipsychotics—olanzapine, quetiapine, and risperidone—any agent in this class can be used in this population, with the choice often depending on how side effects are likely to affect individual patients (Table 3 ).
Pharmacologic attributes may also determine which atypical antipsychotic is used. For example, ziprasidone’s serotonergic profile—with serotonin-1A receptor agonism and serotonin-1D antagonism—may make it useful for patients with mixed states and bipolar depression.26 Aripiprazole offers potential synergism of dopamine agonism with psychostimulant therapy, which could be useful for treating both disruptive behaviors and ADHD.
Table 3
Using atypical antipsychotics to treat comorbid ADHD/bipolar disorder
| Drug | Target dosage (mg/d) | Side effects | Useful in… |
|---|---|---|---|
| Aripiprazole | 10 to 15 | Nausea, vomiting | Comorbid disruptive behavioral disorders, maintenance stabilization |
| Olanzapine | 10 to 20 | Weight gain, hyperlipidemia, hyperglycemia, sedation | Maintenance stabilization |
| Quetiapine | 400 to 600 | Weight gain, sedation | Mixed states, bipolar depression |
| Risperidone | 1 to 2 | Weight gain, hyperprolactinemia, extrapyramidal symptoms | Comorbid disruptive behavioral disorders, including aggression |
| Ziprasidone | 80 to 120 | Cardiac abnormalities, akathisia | Mixed states, bipolar depression |
Related resources
- Child and Adolescent Bipolar Foundation. www.bpkids.org
- Children and Adults with Attention-Deficit Hyperactivity Disorder (CHADD). www.chadd.org
- Findling RF, Kowatch RA, Post RM. P ediatric bipolar disorders: a handbook for clinicians. London: Martin Dunitz Press, 2002.
Drug brand names
- Atomoxetine • Strattera
- Aripiprazole • Abilify
- Divalproex • Depakote
- Olanzapine • Zyprexa
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Ziprasidone • Geodon
Disclosures
Dr. Patel is a consultant to Eli Lilly and Co. and a speaker for Eli Lilly and Co. and Pfizer Inc.
Dr. Sallee receives research support from Otsuka America Pharmaceutical, Pfizer Inc., and Bristol-Myers Squibb Co. and is a consultant or speaker for Eli Lilly and Co, Otsuka America Pharmaceutical, and Pfizer Inc.
1. Geller B, Cooper TB, Sun K, et al. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry 1998;37(2):171-8.
2. Wozniak J, Biederman J, Kiely K, et al. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry 1995;34(7):867-76.
3. Kowatch RA, DelBello MP. Pediatric bipolar disorder: mood swings, irritability are diagnostic cues. Current Psychiatry 2003;2(3):40-7.
4. Quinn CA, Fristad MA. Defining and identifying early onset bipolar spectrum disorder. Curr Psychiatry Rep 2004;6(2):101-7.
5. Bhatara VS, Feil M, Hoagwood K, et al. Trends in combined pharmacotherapy with stimulants for children. Psychiatr Serv 2002;53(3):244.-
6. Zito JM, Safer DJ, dosReis S, et al. Psychotherapeutic medication patterns for youths with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 1999;153(12):1257-63.
7. Wolf DV, Wagner KD. Bipolar disorder in children and adolescents. CNS Spectr 2003;8(12):954-9.
8. Carlson GA, Rapport MD, Kelly KL, Pataki CS. The effects of methylphenidate and lithium on attention and activity level. J Am Acad Child Adolesc Psychiatry 1992;31(2):262-70.
9. Biederman J, Mick E, Prince J, et al. Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder. J Child Adolesc Psychopharmacol 1999;9(4):247-56.
10. Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry 2005;162(1):58-64.
11. Aman MG, Binder C, Turgay A. Risperidone effects in the presence/absence of psychostimulant medicine in children with ADHD, other disruptive behavioral disorders, and subaverage IQ. J Child Adolesc Psychopharmacology 2004;14(2):243-54.
12. Gadow KD, Sverd J, Sprafkin J, et al. Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder. Arch Gen Psychiatry 1999;56(4):330-6.
13. Gaffney GR, Perry PJ, Lund BC, et al. Risperidone versus clonidine in the treatment of children and adolescents with Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry 2002;41(3):330-6.
14. Lombroso PJ, Scahill L, King RA, et al. Risperidone treatment of children and adolescents with chronic tic disorders: a preliminary report. J Am Acad Child Adolesc Psychiatry 1995;34(9):1147-52.
15. Frazier JA, Biederman J, Tohen M, et al. A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol 2001;11(3):239-50.
16. DelBello MP, Schwiers ML, Rosenberg HL, Strakowski SM. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry 2002;41(10):1216-23.
17. Frazier JA, Meyer MC, Biederman J, et al. Risperidone treatment for juvenile bipolar disorder: a retrospective chart review. J Am Acad Child Adolesc Psychiatry 1999;38(8):960-5.
18. Pavuluri MN, Henry DB, Devineni B, et al. A pharmacotherapy algorithm for stabilization and maintenance of pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry 2004;43(7):859-67.
19. Kowatch RA, Fristad M, Birmaher B, et al. Treatment guidelines for children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005;44(3):213-35.
20. Findling RL, McNamara NK. Atypical antipsychotics in the treatment of children and adolescents: clinical applications. J Clin Psychiatry 2004;65(suppl 6):30-44.
21. Kowatch RA, Sethuraman G, Hume JH, et al. Combination pharmacotherapy in children and adolescents with bipolar disorder. Biol Psychiatry 2003;53(11):978-84.
22. Koehler-Troy C, Strober M, Malenbaum R. Methylphenidate-induced mania in a prepubertal child. J Clin Psychiatry 1986;47(11):566-7.
23. Craney J, Geller B. Clinical implications of antidepressant and stimulant use on switching from depression to mania in children. J Child Adolesc Psychopharmacol 2003;13(2):201-4.
24. Galanter CA, Carlson GA, Jensen PS, et al. Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial. J Child Adolesc Psychopharmacol 2003;13(2):123-36.
25. Henderson TA, Hartman K. Aggression, mania, and hypomania induction associated with atomoxetine. Pediatrics 2004;114(3):895-6.
26. Sallee FR, Gilbert DL, Vinks AA, et al. Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission. J Am Acad Child Adolesc Psychiatry 2003;42(8):902-7.
1. Geller B, Cooper TB, Sun K, et al. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry 1998;37(2):171-8.
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