Current Psychiatry

History: From sociable to sullen

Julie, a Hispanic/Native American, was adopted by a Caucasian couple when she was 6 weeks old. Before age 12, she had no psychiatric problems and was medically healthy though slightly overweight.

At age 12, Julie started having episodes of brooding depression, verbal and physical aggression, and impulsive suicidal behavior. She also began suffering intermittent migraines and having trouble falling asleep. She insisted on sleeping with her parents or with a nightlight in her room.

Once a sociable girl who enjoyed being in the middle school chorus and band, Julie suddenly became sullen and defiant. She dropped out of afterschool activities and stopped socializing with peers except for her best friend, Sheila, age 12, and Mark, age 13, an “almost boyfriend” who lived next door.

Julie also started arguing with her mother, often yelling and screaming when approached with minor requests. Sometimes, Julie hit and pushed her. A psychiatrist diagnosed the 12-year-old with major depressive disorder and prescribed fluoxetine, dosage unknown.

Soon after Julie’s symptoms surfaced, her adoptive father, a sales representative, was laid off. He found work in another state; the family left an ethnically diverse city for a predominantly Caucasian rural area. There, Julie completed middle school and her freshman year of high school, and lost contact with Sheila and Mark.

Midway through her freshman year, Julie tried to induce vomiting after eating so that she would lose weight and “fit in better with the other girls.” She stopped this at the end of the school year.

The following fall, 5 weeks into her sophomore year, she dropped out of high school and was ultimately enrolled in home school.

Treatment: 4 hospitalizations in 3 years

Between ages 12 and 15, Julie was hospitalized four times for outbursts of violence with impulsive self-harm. She “overdosed” on eight aceta-minophen/diphenhydramine tablets on one occasion and superficially cut her forearm on another. During these episodes, she said, she heard voices telling her to harm her mother and herself.

During this period, Julie was diagnosed as having schizophrenia, major depressive disorder, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). Numerous antidepressant and mood stabilizer regimens produced no lasting improvement, though her angry and violent episodes became less frequent.

poll here

The authors’ observations

Although Julie’s psychotic symptoms might suggest an evolving disorder such as schizophrenia, no clear pattern supports this diagnosis. Also:

• Onset at age 12 is unusual. Schizophrenia typically begins in late teens to early adulthood.
  
• Julie showed no premorbid personality problems—found in up to one-third of patients with chronic schizophrenia—and no premorbid adjustment difficulties resulting from negative symptoms, cognitive deficits, or poor social function.¹
  

Julie’s birth parents’ mental health history would offer crucial information, but this was not available.

Continued history: ‘I left my body’

Shortly after her 15th birthday, Julie broke down and told her parents that 3 years earlier, four boys had gang-raped her while she was “on a first date” with one of them at a school football game. She said one attacker held a knife to her throat, and they threatened to kill her friend Sheila if anyone was told. Julie said she felt so terrorized that “I left my body and watched what was happening.”

After the rape, Julie went home, showered, and went to bed. She said she felt “emotionally numb” for 2 months, during which she threw herself into schoolwork, stopped attending after-school events, and began arguing with her parents. She developed nightmares of the trauma and, eventually, auditory command hallucinations. When stressed, she has “out of body” feelings lasting several minutes.

The parents, though angry at Julie‘s attackers, did not seek legal counsel or report the rape to authorities because they felt too much time had passed. They sought support from a counselor, who referred their daughter to a male psychiatrist for medication management. Julie, now age 16, preferred to be treated by a woman, so her care was transferred to our clinic.

Based on clinical observations, Julie gets along well with her father. She complains that her mother is overprotective yet Julie cannot bear to be separated from her for even a couple hours. She resents her mother’s overinvolvement but relies on it for emotional regulation. Her mother has been treated for major depressive disorder, generalized anxiety disorder, and alcohol dependence. These were in sustained remission when Julie presented to us.

At presentation, we diagnosed Julie as having chronic posttraumatic stress disorder (PTSD), recurrent major depressive disorder, and eating disorder not otherwise specified. At 5 feet, 7 inches and 190 pounds, her body mass index is 30 kg/m², indicating clinical obesity. She has been taking duloxetine, 60 mg/d, extended release dextroamphetamine, 20 mg/d, aripiprazole, 20 mg/d, and amitriptyline, 10 mg/d nightly. She also has been taking sumatriptan, 100 mg as needed, for migraines.

poll here

The authors’ observations

After a life-threatening sexual assault, Julie suddenly became irritable and hostile. She could not keep relationships, yet she feared being alone. She impulsively hurt herself, experienced nightmares, and systematically avoided school activities. These behaviors suggest PTSD,¹ which is prevalent among sexual assault victims (Box 1). For 3 years, however, psychiatrists kept missing the diagnosis as Julie kept her shame a secret.

Julie tells us that she re-experiences trauma-related dysphoria when exposed to cues, such as the anniversary of the rape. She endorses avoidance symptoms, including feelings of estrangement from her family and friends. She shuns thoughts, feelings, places, and conversations associated with the trauma, which partly explains her refusal to stay in school. She reports arousal symptoms, including difficulty falling and staying asleep and fears of harm if left alone, even during the day. At night she has rituals for checking windows and doors to ensure they are locked.

Julie’s decision to hide her trauma was understandable given her age and developmental phase. For a teenager trying to separate from her parents and fit in at school, the humiliation was overwhelming. She lacked the cognitive tools to process and describe her experience. She was assaulted while on a date, normally a positive rite of passage. Further, as a young Hispanic/Native American, Julie feared disappointing her Caucasian parents by not fitting in at school.

When a previously well-adjusted teenager presents with sudden-onset behavioral problems, ask about past or recent trauma. Watch for contextual, developmental, and sociocultural factors that may prevent the youth from disclosing embarrassing events.

Also question the diagnosis if several adequate medication trials have failed. Check for comorbidities, lack of adherence, or other circumstances that can hamper response to treatment.

Box 1

Factors that may signal ptsd

American Psychiatric Association (APA) practice guidelines for treating PTSD list several factors to consider if you suspect this diagnosis:⁵

Impulsive and episodic aggression can result from an anticipatory bias that increases readiness for “fight, flight, or freeze.” For Julie, this turned previously comfortable interactions into dissonance and conflict.

Self-injurious and suicidal behaviors often occur when trauma creates stigma, shame, or guilt. Julie felt these emotions while trying to establish herself in a new community and school. Her obesity and ethnic background further set her apart from peers. She also left behind friends who provided emotional support outside the home and helped her differentiate from her mother.

Trauma during early adolescence can impair age-appropriate development, making it difficult to develop a stable self-image, consolidate and integrate the personality, and form relationships. At age 16, poor self-image and maladaptive coping strategies were an enduring pattern in Julie’s life.

Psychiatric comorbidities. Many patients with PTSD develop psychiatric comorbidities that exaggerate symptoms, making the disorder more difficult to detect and treat. Julie’s depression increased her avoidance tendencies and rein-forced her isolation. Difficulty concentrating—misdiagnosed as ADHD—deterred her from engaging in school. Dissociative symptoms related to PTSD impaired her reality testing, diminishing her ability to interact with others.

Treatment: Medication change

We continued extended-release dextroamphetamine, 20 mg/d, as Julie felt the medication helped her focus on her schoolwork. We also:

• weaned her off aripiprazole, which was not helping her symptoms
  
• stopped amitriptyline and duloxetine because of her history of impulsive overdose and to reduce side-effect risk from polypharmacy
  
• titrated fluoxetine to 40 mg/d to treat her ongoing chronic depression and added trazodone, 50 mg/d as needed, to help her sleep
  
• stopped sumatriptan, as the headaches remitted after Julie’s eyes were tested and eyeglasses prescribed.
  

poll here

The authors’ observations

Medication. APA treatment guidelines support using SSRIs to treat all three PTSD symptom clusters—re-experiencing, avoidance, and hyperarousal—as well as coexisting depression. Evidence also supports use of the tricyclics amitriptyline and imipramine and some monoamine oxidase inhibitors (MAOIs).^6-10 Dietary restrictions associated with MAOIs, however, can pose a problem for teenagers.

Benzodiazepines can decrease anxiety and improve sleep, but they can be addictive and their efficacy in treating PTSD has not been established. Alpha-2-adrenergic agonists such as prazosin and clonidine may decrease hyperarousal and trauma-related nightmares.^11,12

Obtain informed parental consent before starting a child or adolescent on an antidepressant. These medications contain a black-box warning that the drug may increase suicide risk in youths.

Psychotherapy. Varying levels of evidence support psychotherapy models in PTSD (Box 2). Julie can benefit from psychoeducation, supportive therapy, psychodynamic psychotherapy, and cautious re-exposure to trauma where possible.

Psychoeducation provided a safe starting point for Julie’s therapy, engaged her parents and select school counselors and teachers, and helped her understand PTSD’s effects. This allowed us to teach stress reduction and coping strategies.

Supportive techniques helped Julie contain painful affects. She could then network with community resources such as AlaTeen and a peer support group via a local Native American mental health program. This approach helped us gain Julie’s trust, and we anticipate more in-depth work with time.

Trauma re-exposure helps some patients but worsens others’ symptoms. For Julie, trauma re-exposure has been minimal because of the many other issues she was facing.

Developing a trusting relationship over time is crucial to successful trauma re-exposure. Re-exposure should be gradual to keep affective arousal moderate. This will minimize dissociation and affective flooding, which can frustrate treatment.

Cognitive-behavioral therapy (CBT) might help Julie understand the automatic thoughts of failure and defeat that flood her when she is stressed. CBT could help her master her feelings and lay a foundation for improved coping.

Psychodynamic psychotherapy may be started later to help Julie verbalize feelings and modulate how she expresses affect. This model could promote her development, improve her self-image, and treat her depression.

Box 2

Follow-up: Back to school

After 2 months under our care, Julie begins to show improvement. Because of her progress and the fact that her parents drive 45 minutes each way to get to our clinic, we reduce visit frequency from weekly to biweekly.

Julie now attends school 2 hours daily, is earning additional credits through home study, and plans to graduate early and attend community college. Her depression has lifted, and she continues to take fluoxetine, 40 mg/d and extended-release dextroamphetamine, 20 mg/d. She still struggles with social isolation, failure to reach age-appropriate developmental milestones, and a poor body image.

Related resources

• American Psychiatric Association. Practice guideline for treating acute stress disorder and posttraumatic stress disorder. www.psych.org/psych_pract/treatg/pg/PTSD-PG-PartsA-B-C-New.pdf
  
• National Center for Post-Traumatic Stress Disorder. Information on obtaining Impact of Events Scale and Davidson Trauma Scale. www.ncptsd.va.gov/publications/assessment/adult_self_report.html
  

• Amitriptyline • Elavil
  
• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine (extended-release) • Adderall XR
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Imipramine • Tofranil
  
• Phenelzine • Nardil
  
• Prazosin • Minipress
  
• Sumatriptan • Imitrex
  
• Trazodone • Desyrel
  

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Mossefin reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Acknowledgements

The authors thank Larry Schwartz, MD, for his help in preparing this article for publication.

History: From sociable to sullen

Julie, a Hispanic/Native American, was adopted by a Caucasian couple when she was 6 weeks old. Before age 12, she had no psychiatric problems and was medically healthy though slightly overweight.

At age 12, Julie started having episodes of brooding depression, verbal and physical aggression, and impulsive suicidal behavior. She also began suffering intermittent migraines and having trouble falling asleep. She insisted on sleeping with her parents or with a nightlight in her room.

Once a sociable girl who enjoyed being in the middle school chorus and band, Julie suddenly became sullen and defiant. She dropped out of afterschool activities and stopped socializing with peers except for her best friend, Sheila, age 12, and Mark, age 13, an “almost boyfriend” who lived next door.

Julie also started arguing with her mother, often yelling and screaming when approached with minor requests. Sometimes, Julie hit and pushed her. A psychiatrist diagnosed the 12-year-old with major depressive disorder and prescribed fluoxetine, dosage unknown.

Soon after Julie’s symptoms surfaced, her adoptive father, a sales representative, was laid off. He found work in another state; the family left an ethnically diverse city for a predominantly Caucasian rural area. There, Julie completed middle school and her freshman year of high school, and lost contact with Sheila and Mark.

Midway through her freshman year, Julie tried to induce vomiting after eating so that she would lose weight and “fit in better with the other girls.” She stopped this at the end of the school year.

The following fall, 5 weeks into her sophomore year, she dropped out of high school and was ultimately enrolled in home school.

Treatment: 4 hospitalizations in 3 years

Between ages 12 and 15, Julie was hospitalized four times for outbursts of violence with impulsive self-harm. She “overdosed” on eight aceta-minophen/diphenhydramine tablets on one occasion and superficially cut her forearm on another. During these episodes, she said, she heard voices telling her to harm her mother and herself.

During this period, Julie was diagnosed as having schizophrenia, major depressive disorder, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). Numerous antidepressant and mood stabilizer regimens produced no lasting improvement, though her angry and violent episodes became less frequent.

poll here

The authors’ observations

Although Julie’s psychotic symptoms might suggest an evolving disorder such as schizophrenia, no clear pattern supports this diagnosis. Also:

• Onset at age 12 is unusual. Schizophrenia typically begins in late teens to early adulthood.
  
• Julie showed no premorbid personality problems—found in up to one-third of patients with chronic schizophrenia—and no premorbid adjustment difficulties resulting from negative symptoms, cognitive deficits, or poor social function.¹
  

Julie’s birth parents’ mental health history would offer crucial information, but this was not available.

Continued history: ‘I left my body’

Shortly after her 15th birthday, Julie broke down and told her parents that 3 years earlier, four boys had gang-raped her while she was “on a first date” with one of them at a school football game. She said one attacker held a knife to her throat, and they threatened to kill her friend Sheila if anyone was told. Julie said she felt so terrorized that “I left my body and watched what was happening.”

After the rape, Julie went home, showered, and went to bed. She said she felt “emotionally numb” for 2 months, during which she threw herself into schoolwork, stopped attending after-school events, and began arguing with her parents. She developed nightmares of the trauma and, eventually, auditory command hallucinations. When stressed, she has “out of body” feelings lasting several minutes.

The parents, though angry at Julie‘s attackers, did not seek legal counsel or report the rape to authorities because they felt too much time had passed. They sought support from a counselor, who referred their daughter to a male psychiatrist for medication management. Julie, now age 16, preferred to be treated by a woman, so her care was transferred to our clinic.

Based on clinical observations, Julie gets along well with her father. She complains that her mother is overprotective yet Julie cannot bear to be separated from her for even a couple hours. She resents her mother’s overinvolvement but relies on it for emotional regulation. Her mother has been treated for major depressive disorder, generalized anxiety disorder, and alcohol dependence. These were in sustained remission when Julie presented to us.

At presentation, we diagnosed Julie as having chronic posttraumatic stress disorder (PTSD), recurrent major depressive disorder, and eating disorder not otherwise specified. At 5 feet, 7 inches and 190 pounds, her body mass index is 30 kg/m², indicating clinical obesity. She has been taking duloxetine, 60 mg/d, extended release dextroamphetamine, 20 mg/d, aripiprazole, 20 mg/d, and amitriptyline, 10 mg/d nightly. She also has been taking sumatriptan, 100 mg as needed, for migraines.

poll here

The authors’ observations

After a life-threatening sexual assault, Julie suddenly became irritable and hostile. She could not keep relationships, yet she feared being alone. She impulsively hurt herself, experienced nightmares, and systematically avoided school activities. These behaviors suggest PTSD,¹ which is prevalent among sexual assault victims (Box 1). For 3 years, however, psychiatrists kept missing the diagnosis as Julie kept her shame a secret.

Julie tells us that she re-experiences trauma-related dysphoria when exposed to cues, such as the anniversary of the rape. She endorses avoidance symptoms, including feelings of estrangement from her family and friends. She shuns thoughts, feelings, places, and conversations associated with the trauma, which partly explains her refusal to stay in school. She reports arousal symptoms, including difficulty falling and staying asleep and fears of harm if left alone, even during the day. At night she has rituals for checking windows and doors to ensure they are locked.

Julie’s decision to hide her trauma was understandable given her age and developmental phase. For a teenager trying to separate from her parents and fit in at school, the humiliation was overwhelming. She lacked the cognitive tools to process and describe her experience. She was assaulted while on a date, normally a positive rite of passage. Further, as a young Hispanic/Native American, Julie feared disappointing her Caucasian parents by not fitting in at school.

When a previously well-adjusted teenager presents with sudden-onset behavioral problems, ask about past or recent trauma. Watch for contextual, developmental, and sociocultural factors that may prevent the youth from disclosing embarrassing events.

Also question the diagnosis if several adequate medication trials have failed. Check for comorbidities, lack of adherence, or other circumstances that can hamper response to treatment.

Box 1

Factors that may signal ptsd

American Psychiatric Association (APA) practice guidelines for treating PTSD list several factors to consider if you suspect this diagnosis:⁵

Impulsive and episodic aggression can result from an anticipatory bias that increases readiness for “fight, flight, or freeze.” For Julie, this turned previously comfortable interactions into dissonance and conflict.

Self-injurious and suicidal behaviors often occur when trauma creates stigma, shame, or guilt. Julie felt these emotions while trying to establish herself in a new community and school. Her obesity and ethnic background further set her apart from peers. She also left behind friends who provided emotional support outside the home and helped her differentiate from her mother.

Trauma during early adolescence can impair age-appropriate development, making it difficult to develop a stable self-image, consolidate and integrate the personality, and form relationships. At age 16, poor self-image and maladaptive coping strategies were an enduring pattern in Julie’s life.

Psychiatric comorbidities. Many patients with PTSD develop psychiatric comorbidities that exaggerate symptoms, making the disorder more difficult to detect and treat. Julie’s depression increased her avoidance tendencies and rein-forced her isolation. Difficulty concentrating—misdiagnosed as ADHD—deterred her from engaging in school. Dissociative symptoms related to PTSD impaired her reality testing, diminishing her ability to interact with others.

Treatment: Medication change

We continued extended-release dextroamphetamine, 20 mg/d, as Julie felt the medication helped her focus on her schoolwork. We also:

• weaned her off aripiprazole, which was not helping her symptoms
  
• stopped amitriptyline and duloxetine because of her history of impulsive overdose and to reduce side-effect risk from polypharmacy
  
• titrated fluoxetine to 40 mg/d to treat her ongoing chronic depression and added trazodone, 50 mg/d as needed, to help her sleep
  
• stopped sumatriptan, as the headaches remitted after Julie’s eyes were tested and eyeglasses prescribed.
  

poll here

The authors’ observations

Medication. APA treatment guidelines support using SSRIs to treat all three PTSD symptom clusters—re-experiencing, avoidance, and hyperarousal—as well as coexisting depression. Evidence also supports use of the tricyclics amitriptyline and imipramine and some monoamine oxidase inhibitors (MAOIs).^6-10 Dietary restrictions associated with MAOIs, however, can pose a problem for teenagers.

Benzodiazepines can decrease anxiety and improve sleep, but they can be addictive and their efficacy in treating PTSD has not been established. Alpha-2-adrenergic agonists such as prazosin and clonidine may decrease hyperarousal and trauma-related nightmares.^11,12

Obtain informed parental consent before starting a child or adolescent on an antidepressant. These medications contain a black-box warning that the drug may increase suicide risk in youths.

Psychotherapy. Varying levels of evidence support psychotherapy models in PTSD (Box 2). Julie can benefit from psychoeducation, supportive therapy, psychodynamic psychotherapy, and cautious re-exposure to trauma where possible.

Psychoeducation provided a safe starting point for Julie’s therapy, engaged her parents and select school counselors and teachers, and helped her understand PTSD’s effects. This allowed us to teach stress reduction and coping strategies.

Supportive techniques helped Julie contain painful affects. She could then network with community resources such as AlaTeen and a peer support group via a local Native American mental health program. This approach helped us gain Julie’s trust, and we anticipate more in-depth work with time.

Trauma re-exposure helps some patients but worsens others’ symptoms. For Julie, trauma re-exposure has been minimal because of the many other issues she was facing.

Developing a trusting relationship over time is crucial to successful trauma re-exposure. Re-exposure should be gradual to keep affective arousal moderate. This will minimize dissociation and affective flooding, which can frustrate treatment.

Cognitive-behavioral therapy (CBT) might help Julie understand the automatic thoughts of failure and defeat that flood her when she is stressed. CBT could help her master her feelings and lay a foundation for improved coping.

Psychodynamic psychotherapy may be started later to help Julie verbalize feelings and modulate how she expresses affect. This model could promote her development, improve her self-image, and treat her depression.

Box 2

Follow-up: Back to school

After 2 months under our care, Julie begins to show improvement. Because of her progress and the fact that her parents drive 45 minutes each way to get to our clinic, we reduce visit frequency from weekly to biweekly.

Julie now attends school 2 hours daily, is earning additional credits through home study, and plans to graduate early and attend community college. Her depression has lifted, and she continues to take fluoxetine, 40 mg/d and extended-release dextroamphetamine, 20 mg/d. She still struggles with social isolation, failure to reach age-appropriate developmental milestones, and a poor body image.

Related resources

• American Psychiatric Association. Practice guideline for treating acute stress disorder and posttraumatic stress disorder. www.psych.org/psych_pract/treatg/pg/PTSD-PG-PartsA-B-C-New.pdf
  
• National Center for Post-Traumatic Stress Disorder. Information on obtaining Impact of Events Scale and Davidson Trauma Scale. www.ncptsd.va.gov/publications/assessment/adult_self_report.html
  

• Amitriptyline • Elavil
  
• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine (extended-release) • Adderall XR
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Imipramine • Tofranil
  
• Phenelzine • Nardil
  
• Prazosin • Minipress
  
• Sumatriptan • Imitrex
  
• Trazodone • Desyrel
  

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Mossefin reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Acknowledgements

The authors thank Larry Schwartz, MD, for his help in preparing this article for publication.

History: From sociable to sullen

Julie, a Hispanic/Native American, was adopted by a Caucasian couple when she was 6 weeks old. Before age 12, she had no psychiatric problems and was medically healthy though slightly overweight.

At age 12, Julie started having episodes of brooding depression, verbal and physical aggression, and impulsive suicidal behavior. She also began suffering intermittent migraines and having trouble falling asleep. She insisted on sleeping with her parents or with a nightlight in her room.

Once a sociable girl who enjoyed being in the middle school chorus and band, Julie suddenly became sullen and defiant. She dropped out of afterschool activities and stopped socializing with peers except for her best friend, Sheila, age 12, and Mark, age 13, an “almost boyfriend” who lived next door.

Julie also started arguing with her mother, often yelling and screaming when approached with minor requests. Sometimes, Julie hit and pushed her. A psychiatrist diagnosed the 12-year-old with major depressive disorder and prescribed fluoxetine, dosage unknown.

Soon after Julie’s symptoms surfaced, her adoptive father, a sales representative, was laid off. He found work in another state; the family left an ethnically diverse city for a predominantly Caucasian rural area. There, Julie completed middle school and her freshman year of high school, and lost contact with Sheila and Mark.

Midway through her freshman year, Julie tried to induce vomiting after eating so that she would lose weight and “fit in better with the other girls.” She stopped this at the end of the school year.

The following fall, 5 weeks into her sophomore year, she dropped out of high school and was ultimately enrolled in home school.

Treatment: 4 hospitalizations in 3 years

Between ages 12 and 15, Julie was hospitalized four times for outbursts of violence with impulsive self-harm. She “overdosed” on eight aceta-minophen/diphenhydramine tablets on one occasion and superficially cut her forearm on another. During these episodes, she said, she heard voices telling her to harm her mother and herself.

During this period, Julie was diagnosed as having schizophrenia, major depressive disorder, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). Numerous antidepressant and mood stabilizer regimens produced no lasting improvement, though her angry and violent episodes became less frequent.

poll here

The authors’ observations

Although Julie’s psychotic symptoms might suggest an evolving disorder such as schizophrenia, no clear pattern supports this diagnosis. Also:

• Onset at age 12 is unusual. Schizophrenia typically begins in late teens to early adulthood.
  
• Julie showed no premorbid personality problems—found in up to one-third of patients with chronic schizophrenia—and no premorbid adjustment difficulties resulting from negative symptoms, cognitive deficits, or poor social function.¹
  

Julie’s birth parents’ mental health history would offer crucial information, but this was not available.

Continued history: ‘I left my body’

Shortly after her 15th birthday, Julie broke down and told her parents that 3 years earlier, four boys had gang-raped her while she was “on a first date” with one of them at a school football game. She said one attacker held a knife to her throat, and they threatened to kill her friend Sheila if anyone was told. Julie said she felt so terrorized that “I left my body and watched what was happening.”

After the rape, Julie went home, showered, and went to bed. She said she felt “emotionally numb” for 2 months, during which she threw herself into schoolwork, stopped attending after-school events, and began arguing with her parents. She developed nightmares of the trauma and, eventually, auditory command hallucinations. When stressed, she has “out of body” feelings lasting several minutes.

The parents, though angry at Julie‘s attackers, did not seek legal counsel or report the rape to authorities because they felt too much time had passed. They sought support from a counselor, who referred their daughter to a male psychiatrist for medication management. Julie, now age 16, preferred to be treated by a woman, so her care was transferred to our clinic.

Based on clinical observations, Julie gets along well with her father. She complains that her mother is overprotective yet Julie cannot bear to be separated from her for even a couple hours. She resents her mother’s overinvolvement but relies on it for emotional regulation. Her mother has been treated for major depressive disorder, generalized anxiety disorder, and alcohol dependence. These were in sustained remission when Julie presented to us.

At presentation, we diagnosed Julie as having chronic posttraumatic stress disorder (PTSD), recurrent major depressive disorder, and eating disorder not otherwise specified. At 5 feet, 7 inches and 190 pounds, her body mass index is 30 kg/m², indicating clinical obesity. She has been taking duloxetine, 60 mg/d, extended release dextroamphetamine, 20 mg/d, aripiprazole, 20 mg/d, and amitriptyline, 10 mg/d nightly. She also has been taking sumatriptan, 100 mg as needed, for migraines.

poll here

The authors’ observations

After a life-threatening sexual assault, Julie suddenly became irritable and hostile. She could not keep relationships, yet she feared being alone. She impulsively hurt herself, experienced nightmares, and systematically avoided school activities. These behaviors suggest PTSD,¹ which is prevalent among sexual assault victims (Box 1). For 3 years, however, psychiatrists kept missing the diagnosis as Julie kept her shame a secret.

Julie tells us that she re-experiences trauma-related dysphoria when exposed to cues, such as the anniversary of the rape. She endorses avoidance symptoms, including feelings of estrangement from her family and friends. She shuns thoughts, feelings, places, and conversations associated with the trauma, which partly explains her refusal to stay in school. She reports arousal symptoms, including difficulty falling and staying asleep and fears of harm if left alone, even during the day. At night she has rituals for checking windows and doors to ensure they are locked.

Julie’s decision to hide her trauma was understandable given her age and developmental phase. For a teenager trying to separate from her parents and fit in at school, the humiliation was overwhelming. She lacked the cognitive tools to process and describe her experience. She was assaulted while on a date, normally a positive rite of passage. Further, as a young Hispanic/Native American, Julie feared disappointing her Caucasian parents by not fitting in at school.

When a previously well-adjusted teenager presents with sudden-onset behavioral problems, ask about past or recent trauma. Watch for contextual, developmental, and sociocultural factors that may prevent the youth from disclosing embarrassing events.

Also question the diagnosis if several adequate medication trials have failed. Check for comorbidities, lack of adherence, or other circumstances that can hamper response to treatment.

Box 1

Factors that may signal ptsd

American Psychiatric Association (APA) practice guidelines for treating PTSD list several factors to consider if you suspect this diagnosis:⁵

Impulsive and episodic aggression can result from an anticipatory bias that increases readiness for “fight, flight, or freeze.” For Julie, this turned previously comfortable interactions into dissonance and conflict.

Self-injurious and suicidal behaviors often occur when trauma creates stigma, shame, or guilt. Julie felt these emotions while trying to establish herself in a new community and school. Her obesity and ethnic background further set her apart from peers. She also left behind friends who provided emotional support outside the home and helped her differentiate from her mother.

Trauma during early adolescence can impair age-appropriate development, making it difficult to develop a stable self-image, consolidate and integrate the personality, and form relationships. At age 16, poor self-image and maladaptive coping strategies were an enduring pattern in Julie’s life.

Psychiatric comorbidities. Many patients with PTSD develop psychiatric comorbidities that exaggerate symptoms, making the disorder more difficult to detect and treat. Julie’s depression increased her avoidance tendencies and rein-forced her isolation. Difficulty concentrating—misdiagnosed as ADHD—deterred her from engaging in school. Dissociative symptoms related to PTSD impaired her reality testing, diminishing her ability to interact with others.

Treatment: Medication change

We continued extended-release dextroamphetamine, 20 mg/d, as Julie felt the medication helped her focus on her schoolwork. We also:

• weaned her off aripiprazole, which was not helping her symptoms
  
• stopped amitriptyline and duloxetine because of her history of impulsive overdose and to reduce side-effect risk from polypharmacy
  
• titrated fluoxetine to 40 mg/d to treat her ongoing chronic depression and added trazodone, 50 mg/d as needed, to help her sleep
  
• stopped sumatriptan, as the headaches remitted after Julie’s eyes were tested and eyeglasses prescribed.
  

poll here

The authors’ observations

Medication. APA treatment guidelines support using SSRIs to treat all three PTSD symptom clusters—re-experiencing, avoidance, and hyperarousal—as well as coexisting depression. Evidence also supports use of the tricyclics amitriptyline and imipramine and some monoamine oxidase inhibitors (MAOIs).^6-10 Dietary restrictions associated with MAOIs, however, can pose a problem for teenagers.

Benzodiazepines can decrease anxiety and improve sleep, but they can be addictive and their efficacy in treating PTSD has not been established. Alpha-2-adrenergic agonists such as prazosin and clonidine may decrease hyperarousal and trauma-related nightmares.^11,12

Obtain informed parental consent before starting a child or adolescent on an antidepressant. These medications contain a black-box warning that the drug may increase suicide risk in youths.

Psychotherapy. Varying levels of evidence support psychotherapy models in PTSD (Box 2). Julie can benefit from psychoeducation, supportive therapy, psychodynamic psychotherapy, and cautious re-exposure to trauma where possible.

Psychoeducation provided a safe starting point for Julie’s therapy, engaged her parents and select school counselors and teachers, and helped her understand PTSD’s effects. This allowed us to teach stress reduction and coping strategies.

Supportive techniques helped Julie contain painful affects. She could then network with community resources such as AlaTeen and a peer support group via a local Native American mental health program. This approach helped us gain Julie’s trust, and we anticipate more in-depth work with time.

Trauma re-exposure helps some patients but worsens others’ symptoms. For Julie, trauma re-exposure has been minimal because of the many other issues she was facing.

Developing a trusting relationship over time is crucial to successful trauma re-exposure. Re-exposure should be gradual to keep affective arousal moderate. This will minimize dissociation and affective flooding, which can frustrate treatment.

Cognitive-behavioral therapy (CBT) might help Julie understand the automatic thoughts of failure and defeat that flood her when she is stressed. CBT could help her master her feelings and lay a foundation for improved coping.

Psychodynamic psychotherapy may be started later to help Julie verbalize feelings and modulate how she expresses affect. This model could promote her development, improve her self-image, and treat her depression.

Box 2

Follow-up: Back to school

After 2 months under our care, Julie begins to show improvement. Because of her progress and the fact that her parents drive 45 minutes each way to get to our clinic, we reduce visit frequency from weekly to biweekly.

Julie now attends school 2 hours daily, is earning additional credits through home study, and plans to graduate early and attend community college. Her depression has lifted, and she continues to take fluoxetine, 40 mg/d and extended-release dextroamphetamine, 20 mg/d. She still struggles with social isolation, failure to reach age-appropriate developmental milestones, and a poor body image.

Related resources

• American Psychiatric Association. Practice guideline for treating acute stress disorder and posttraumatic stress disorder. www.psych.org/psych_pract/treatg/pg/PTSD-PG-PartsA-B-C-New.pdf
  
• National Center for Post-Traumatic Stress Disorder. Information on obtaining Impact of Events Scale and Davidson Trauma Scale. www.ncptsd.va.gov/publications/assessment/adult_self_report.html
  

• Amitriptyline • Elavil
  
• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine (extended-release) • Adderall XR
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Imipramine • Tofranil
  
• Phenelzine • Nardil
  
• Prazosin • Minipress
  
• Sumatriptan • Imitrex
  
• Trazodone • Desyrel
  

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Mossefin reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Acknowledgements

The authors thank Larry Schwartz, MD, for his help in preparing this article for publication.

Investigators faced a dilemma while designing the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). More than 200 enrollees with chronic schizophrenia had pre-existing tardive dyskinesia (TD). Would it be ethical to give them the antipsychotic most likely to worsen their TD? Would exempting them from taking that drug influence the trial’s outcome?

This issue and others had to be resolved before the largest controlled study of “real world” schizophrenia could begin. Now that data are unfolding, groups with diverse agendas are debating CATIE’s methods and surprising results. This article describes how the trial’s design and findings could transform public policy and clinical practice.

poll here

Efficacy vs Effectiveness

The National Institute of Mental Health funded the prospective CATIE schizophrenia study to compare the effectiveness of atypical antipsychotics versus each other and versus a first-generation (typical) antipsychotic.

All approved atypicals have shown similar efficacy compared with placebo in short-term trials (usually 6 weeks).¹ The CATIE trial’s rationale is that short-term efficacy studies required for FDA approval may not necessarily reflect the drugs’ effectiveness in long-term schizophrenia management. Effectiveness measures take into account efficacy as well as safety, tolerability, and unpredictable patient behaviors in the real world.

CATIE’s ‘Real World’ Patients

CATIE investigators enrolled a community sample of chronic schizophrenia patients similar to those many psychiatrists see. Very liberal inclusion and exclusion criteria (Table 1) allowed enrollees to have a history of substance abuse, comorbid psychiatric or medical disorders, be receiving other medications, or show evidence of TD. Their schizophrenia ranged from minimal to severe.^2,3

The 1,493 patients who completed the study (Table 2) were enrolled at 57 outpatient treatment settings. One site’s 33 patients were eliminated from analysis because of doubts about the integrity of the data, leaving a total of 1,460 subjects.⁴

Table 1

Criteria for enrolling patients in the CATIE schizophrenia trial

Table 2

CATIE’s 1,460 ‘real world’ schizophrenia patients at trial entry

Medications. Before randomization, 28% of enrollees were not receiving antipsychotics. The remainder were receiving:

• olanzapine (22%)
• risperidone (19%)
• quetiapine (7%)
• ziprasidone (0%; approved after the trial began)
• any combination of olanzapine, risperidone, and quetiapine (7%)
• typical antipsychotics (16%).

Metabolic profile. These outpatients had a high rate of metabolic disorders: 42%—twice the rate in the general population—met criteria for metabolic syndrome,⁵ putting them at high risk to die of cardiovascular causes within 10 years.⁶ They had relatively poor physical health self-ratings and increased somatic preoccupation.⁷ Most worrisome, many were receiving no medications for their metabolic disorders, including 45% of those with diabetes, 89% with hyperlipidemia, and 62% with hypertension.⁸

Substance abuse. At enrollment, 40% of patients were abstinent from substance use, 22% were using substances without abuse or dependence, and 37% had substance abuse or dependence. Compared with nonusers, substance abusers tended to be male with more childhood problems, higher positive symptoms on the Positive and Negative Syndrome Scale (PANSS), and more likely to have had a recent illness exacerbation.⁹

Tardive dyskinesia. The 231 subjects who met criteria for probable TD¹⁰ were older than the overall sample with more years of antipsychotic treatment, especially with conventional neuroleptics and anticholinergics. Substance abuse was associated with TD, as were severity of psychopathology, extrapyramidal symptoms (EPS), and akathisia.¹¹

Violent behavior. A history of serious violent behavior was reported in:

• 5.4% of patients with high positive and low negative PANSS symptom scores
• 1.7% of patients with low positive and high negative PANSS symptom scores.

Consent. Patients’ capacity to give consent to participate in the study was assessed with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Psychosis severity (PANSS positive symptom scale) was not found to affect decision-making capacity, but negative symptoms and diminished working memory did.¹²

CATIE’s Unique Design

Defining effectiveness. CATIE was designed in three phases (Figure). Phase 1—discussed here—was a blinded, controlled comparison of four atypical antipsychotics and perphenazine. Results of phases 2 and 3 have yet to be published. The primary effectiveness endpoint, “all-cause discontinuation,” was defined as:

• lack of efficacy (patient was switched to another drug assigned at random)
• lack of tolerability (patient requested a drug change)
• safety problem (investigator initiated a switch)
• patient’s decision for any reason (often dropping out of the study).

The longer subjects stayed on the first antipsychotic they received, the more effective that drug was considered to be.

Figure CATIE schizophrenia trial design

* Phase 1A: participants with tardive dyskinesia (N=231) do not get randomized to perphenazine; phase 1B: participants who fail perphenazine will be randomized to an atypical (olanzapine, quetiapine, or risperidone) before eligibility for phase 2.
Source: Reference 2.Medications. Three atypicals—risperidone, olanzapine, and quetiapine—were approved for schizophrenia when the trial began in 1999. Recruitment ended in June 2003, the last subject completed the 18-month trial in December 2004, and data analysis began in January 2005. Ziprasidone was added to phase 1 after 40% of the sample had been enrolled, and aripiprazole was included as an option in the unblinded phase 3.

Perphenazine was chosen to represent typical antipsychotics because it has medium potency and less risk of EPS than high-potency drugs such as haloperidol and is associated with less weight gain than low-potency drugs such as thioridazine.

Dosing. Pharmaceutical manufacturers donated the antipsychotics and were invited to recommend their respective drugs’ starting dosages, dose increments, and maximum dosages. Olanzapine’s maker requested a higher starting dosage (7.5 mg/d instead of 5.0 mg/d) and a maximum dosage 50% higher than the FDA-approved range (30 mg/d instead of 20 mg/d). The others recommended the FDA-approved dosage ranges or less:

• quetiapine, 200 to 800 mg/d
• risperidone, 1.5 to 6 mg/d
• ziprasidone, 40 to 160 mg/d
• perphenazine, 8 to 32 mg/d.

The study team accepted their recommendations.

The medications were packaged in identical capsules. Quetiapine and ziprasidone were given twice daily because of product labeling; risperidone, olanzapine, and perphenazine were given once daily to one-half the patients assigned to them and twice daily to the others to prevent raters from guessing which drug a patient was receiving.

Tardive dyskinesia. For ethical reasons, the 231 patients with TD at enrollment were randomly assigned in phase 1 to atypicals but not to perphenazine because of the well-established link between typical antipsychotics and TD. This exception could have contributed to the closer-than-expected differences in EPS and perhaps in efficacy, given reports that TD patients have more negative symptoms and cognitive dysfunction.¹³ However, a statistical analysis took that into account.

CATIE’s Key Findings

Discontinuation. A disappointingly high discontinuation rate (74% overall) within a few months was the most important finding (Table 3). A recent effectiveness study with a design similar to the CATIE trial found a similarly high rate of all-cause discontinuation (70%) in patients with first-episode psychosis.¹⁴ Thus, patient-initiated drug discontinuation appears to be a core illness behavior from schizophrenia onset to chronic illness.

The high discontinuation rate shows that we need to modify our approach to schizophrenia, emphasizing full adherence to antipsychotic therapy from the onset of the illness.

Table 3

All-cause discontinuation rates in the CATIE trial

Effectiveness—measured as all-cause discontinuation or switching—was the primary outcome of phase 1. The unexpected finding that perphenazine and the atypicals had similar effectiveness could influence clinical practice. Insurers, for example, might consider promoting cheaper typical antipsychotics for first-line use. CATIE’s cost-effectiveness arm (Rosenheck et al, submitted for publication) will provide additional data on this issue.

Before rushing to use older antipsychotics as first-line treatments for schizophrenia, however, policymakers should consider three factors in the study design that could have enhanced perphenazine’s efficacy and safety profiles.

First, perphenazine was given at lower dosages (up to 32 mg/d) than “real world” clinicians used a decade ago (up to 64 mg/d). Thus, lower rates of serious side effects, especially TD, might have occurred in the study than in past clinical practice. Since atypical antipsychotics were approved, clinicians see far fewer psychiatric patients with pill-rolling tremors, rigid posture, or a shuffling gait, compared with 10 to 15 years ago when typical antipsychotics were widely used.

Second, perphenazine was associated with the highest EPS rate (17%), though its mean modal dosage (20.8 mg/d) is considered moderate. Discontinuation because of EPS was highest with perphenazine and lowest with quetiapine.

Third, excluding enrollees with TD from perphenazine may have increased perphenazine’s effectiveness, whereas including them in the atypicals groups may have reduced the atypicals’ effectiveness. TD patients are at increased risk to develop EPS; they had more-severe illness and a higher substance abuse rate among CATIE patients.¹¹ Even so, investigators did control for TD in the data analysis and found no significant difference between typical and atypical antipsychotics.

No ‘Winners’ or ‘Losers’

Effectiveness, tolerability, and safety findings for each antipsychotic are compared in Tables 4A and 4B. Careful review shows no clear “winners” or “losers;” each agent has weaknesses but also strengths that may benefit individual patients.

Efficacy. Olanzapine showed a relatively higher efficacy and lower discontinuation rate but also had the highest risk of adverse metabolic effects. Some have attributed its greater efficacy to its higher dosing compared with the other antipsychotics. Some also have argued that the antipsychotics that showed lower efficacy, such as quetiapine and ziprasidone, were underdosed in this chronic schizophrenia population with a mean duration of illness of 14 years. Perphenazine, too, was dosed at the lower end of its range (mean modal dose 20.8 mg/d) compared with the old community standard of 36 to 64 mg/d.

Generally, a mean modal dosage of 20.1 mg/d for olanzapine is considered equivalent to ziprasidone, 160 mg; quetiapine, 800 mg; and risperidone, 6 mg. In CATIE phase 1, mean modal dosages were:

• ziprasidone, 112.8 mg/d (30% below 160 mg)
• quetiapine, 543.4 mg/d (32% below 800)
• risperidone, 3.9 mg/d (35% below 6 mg).

Olanzapine’s starting dosage of 7.5 mg/d was relatively higher than those of the other atypicals, which may have produced more-rapid onset of efficacy.

Switching. Another potential “advantage” for olanzapine was that 22% of subjects were taking it when they enrolled. By random assignment, 23% of patients who were taking olanzapine stayed on olanzapine and did not switch. By comparison:

• No patients assigned to ziprasidone were taking it before entering the trial.
• Only 5% of those taking quetiapine stayed on that drug after randomization.
• Few were receiving perphenazine before enrollment.

Switching antipsychotics may increase side effect risk or efficacy problems. For example, a patient switched from olanzapine or quetiapine to ziprasidone or perphenazine may experience insomnia during the transition, which may lead to tolerability complaints.

Metabolic side effects seen in this trial support past observations and reports that olanzapine is associated with higher risk for weight gain, hyperglycemia, and hyperlipidemia than other antipsychotics.¹⁵ Data on metabolic changes in CATIE patients taking olanzapine are being analyzed.

Hyperprolactinemia was most common with risperidone and practically nonexistent with other antipsychotics—even perphenazine. On the other hand, risperidone had the most favorable tolerability profile. This implies that elevated prolactin does not necessarily lead to antipsychotic discontinuation because of tolerability among patients with schizophrenia.

QTC interval and cataract data were benign across all antipsychotics. These findings appear to exonerate ziprasidone and quetiapine, respectively, which have been perceived as associated with these side effects.

Related resources

• Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study. www.catie.unc.edu/schizophrenia
• Schizophrenia Research Forum. NARSAD, The Mental Health Research Association.www.schizophreniaforum.org

Drug brand names

• Aripiprazole • Abilify
• Olanzapine • Zyprexa
• Perphenazine • Trilafon
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Disclosures

Dr Nasrallah receives grants/research support from AstraZeneca, Janssen Pharmaceutica, Eli Lilly & Co., and Pfizer. He is a consultant, advisory board member, and speaker for Abbott Laboratories, AstraZeneca, Janssen Pharmaceutica, Pfizer, and Shire Pharmaceuticals Group.

Investigators faced a dilemma while designing the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). More than 200 enrollees with chronic schizophrenia had pre-existing tardive dyskinesia (TD). Would it be ethical to give them the antipsychotic most likely to worsen their TD? Would exempting them from taking that drug influence the trial’s outcome?

This issue and others had to be resolved before the largest controlled study of “real world” schizophrenia could begin. Now that data are unfolding, groups with diverse agendas are debating CATIE’s methods and surprising results. This article describes how the trial’s design and findings could transform public policy and clinical practice.

poll here

Efficacy vs Effectiveness

The National Institute of Mental Health funded the prospective CATIE schizophrenia study to compare the effectiveness of atypical antipsychotics versus each other and versus a first-generation (typical) antipsychotic.

All approved atypicals have shown similar efficacy compared with placebo in short-term trials (usually 6 weeks).¹ The CATIE trial’s rationale is that short-term efficacy studies required for FDA approval may not necessarily reflect the drugs’ effectiveness in long-term schizophrenia management. Effectiveness measures take into account efficacy as well as safety, tolerability, and unpredictable patient behaviors in the real world.

CATIE’s ‘Real World’ Patients

CATIE investigators enrolled a community sample of chronic schizophrenia patients similar to those many psychiatrists see. Very liberal inclusion and exclusion criteria (Table 1) allowed enrollees to have a history of substance abuse, comorbid psychiatric or medical disorders, be receiving other medications, or show evidence of TD. Their schizophrenia ranged from minimal to severe.^2,3

The 1,493 patients who completed the study (Table 2) were enrolled at 57 outpatient treatment settings. One site’s 33 patients were eliminated from analysis because of doubts about the integrity of the data, leaving a total of 1,460 subjects.⁴

Table 1

Criteria for enrolling patients in the CATIE schizophrenia trial

Table 2

CATIE’s 1,460 ‘real world’ schizophrenia patients at trial entry

Medications. Before randomization, 28% of enrollees were not receiving antipsychotics. The remainder were receiving:

• olanzapine (22%)
• risperidone (19%)
• quetiapine (7%)
• ziprasidone (0%; approved after the trial began)
• any combination of olanzapine, risperidone, and quetiapine (7%)
• typical antipsychotics (16%).

Metabolic profile. These outpatients had a high rate of metabolic disorders: 42%—twice the rate in the general population—met criteria for metabolic syndrome,⁵ putting them at high risk to die of cardiovascular causes within 10 years.⁶ They had relatively poor physical health self-ratings and increased somatic preoccupation.⁷ Most worrisome, many were receiving no medications for their metabolic disorders, including 45% of those with diabetes, 89% with hyperlipidemia, and 62% with hypertension.⁸

Substance abuse. At enrollment, 40% of patients were abstinent from substance use, 22% were using substances without abuse or dependence, and 37% had substance abuse or dependence. Compared with nonusers, substance abusers tended to be male with more childhood problems, higher positive symptoms on the Positive and Negative Syndrome Scale (PANSS), and more likely to have had a recent illness exacerbation.⁹

Tardive dyskinesia. The 231 subjects who met criteria for probable TD¹⁰ were older than the overall sample with more years of antipsychotic treatment, especially with conventional neuroleptics and anticholinergics. Substance abuse was associated with TD, as were severity of psychopathology, extrapyramidal symptoms (EPS), and akathisia.¹¹

Violent behavior. A history of serious violent behavior was reported in:

• 5.4% of patients with high positive and low negative PANSS symptom scores
• 1.7% of patients with low positive and high negative PANSS symptom scores.

Consent. Patients’ capacity to give consent to participate in the study was assessed with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Psychosis severity (PANSS positive symptom scale) was not found to affect decision-making capacity, but negative symptoms and diminished working memory did.¹²

CATIE’s Unique Design

Defining effectiveness. CATIE was designed in three phases (Figure). Phase 1—discussed here—was a blinded, controlled comparison of four atypical antipsychotics and perphenazine. Results of phases 2 and 3 have yet to be published. The primary effectiveness endpoint, “all-cause discontinuation,” was defined as:

• lack of efficacy (patient was switched to another drug assigned at random)
• lack of tolerability (patient requested a drug change)
• safety problem (investigator initiated a switch)
• patient’s decision for any reason (often dropping out of the study).

The longer subjects stayed on the first antipsychotic they received, the more effective that drug was considered to be.

Figure CATIE schizophrenia trial design

* Phase 1A: participants with tardive dyskinesia (N=231) do not get randomized to perphenazine; phase 1B: participants who fail perphenazine will be randomized to an atypical (olanzapine, quetiapine, or risperidone) before eligibility for phase 2.
Source: Reference 2.Medications. Three atypicals—risperidone, olanzapine, and quetiapine—were approved for schizophrenia when the trial began in 1999. Recruitment ended in June 2003, the last subject completed the 18-month trial in December 2004, and data analysis began in January 2005. Ziprasidone was added to phase 1 after 40% of the sample had been enrolled, and aripiprazole was included as an option in the unblinded phase 3.

Perphenazine was chosen to represent typical antipsychotics because it has medium potency and less risk of EPS than high-potency drugs such as haloperidol and is associated with less weight gain than low-potency drugs such as thioridazine.

Dosing. Pharmaceutical manufacturers donated the antipsychotics and were invited to recommend their respective drugs’ starting dosages, dose increments, and maximum dosages. Olanzapine’s maker requested a higher starting dosage (7.5 mg/d instead of 5.0 mg/d) and a maximum dosage 50% higher than the FDA-approved range (30 mg/d instead of 20 mg/d). The others recommended the FDA-approved dosage ranges or less:

• quetiapine, 200 to 800 mg/d
• risperidone, 1.5 to 6 mg/d
• ziprasidone, 40 to 160 mg/d
• perphenazine, 8 to 32 mg/d.

The study team accepted their recommendations.

The medications were packaged in identical capsules. Quetiapine and ziprasidone were given twice daily because of product labeling; risperidone, olanzapine, and perphenazine were given once daily to one-half the patients assigned to them and twice daily to the others to prevent raters from guessing which drug a patient was receiving.

Tardive dyskinesia. For ethical reasons, the 231 patients with TD at enrollment were randomly assigned in phase 1 to atypicals but not to perphenazine because of the well-established link between typical antipsychotics and TD. This exception could have contributed to the closer-than-expected differences in EPS and perhaps in efficacy, given reports that TD patients have more negative symptoms and cognitive dysfunction.¹³ However, a statistical analysis took that into account.

CATIE’s Key Findings

Discontinuation. A disappointingly high discontinuation rate (74% overall) within a few months was the most important finding (Table 3). A recent effectiveness study with a design similar to the CATIE trial found a similarly high rate of all-cause discontinuation (70%) in patients with first-episode psychosis.¹⁴ Thus, patient-initiated drug discontinuation appears to be a core illness behavior from schizophrenia onset to chronic illness.

The high discontinuation rate shows that we need to modify our approach to schizophrenia, emphasizing full adherence to antipsychotic therapy from the onset of the illness.

Table 3

All-cause discontinuation rates in the CATIE trial

Effectiveness—measured as all-cause discontinuation or switching—was the primary outcome of phase 1. The unexpected finding that perphenazine and the atypicals had similar effectiveness could influence clinical practice. Insurers, for example, might consider promoting cheaper typical antipsychotics for first-line use. CATIE’s cost-effectiveness arm (Rosenheck et al, submitted for publication) will provide additional data on this issue.

Before rushing to use older antipsychotics as first-line treatments for schizophrenia, however, policymakers should consider three factors in the study design that could have enhanced perphenazine’s efficacy and safety profiles.

First, perphenazine was given at lower dosages (up to 32 mg/d) than “real world” clinicians used a decade ago (up to 64 mg/d). Thus, lower rates of serious side effects, especially TD, might have occurred in the study than in past clinical practice. Since atypical antipsychotics were approved, clinicians see far fewer psychiatric patients with pill-rolling tremors, rigid posture, or a shuffling gait, compared with 10 to 15 years ago when typical antipsychotics were widely used.

Second, perphenazine was associated with the highest EPS rate (17%), though its mean modal dosage (20.8 mg/d) is considered moderate. Discontinuation because of EPS was highest with perphenazine and lowest with quetiapine.

Third, excluding enrollees with TD from perphenazine may have increased perphenazine’s effectiveness, whereas including them in the atypicals groups may have reduced the atypicals’ effectiveness. TD patients are at increased risk to develop EPS; they had more-severe illness and a higher substance abuse rate among CATIE patients.¹¹ Even so, investigators did control for TD in the data analysis and found no significant difference between typical and atypical antipsychotics.

No ‘Winners’ or ‘Losers’

Effectiveness, tolerability, and safety findings for each antipsychotic are compared in Tables 4A and 4B. Careful review shows no clear “winners” or “losers;” each agent has weaknesses but also strengths that may benefit individual patients.

Efficacy. Olanzapine showed a relatively higher efficacy and lower discontinuation rate but also had the highest risk of adverse metabolic effects. Some have attributed its greater efficacy to its higher dosing compared with the other antipsychotics. Some also have argued that the antipsychotics that showed lower efficacy, such as quetiapine and ziprasidone, were underdosed in this chronic schizophrenia population with a mean duration of illness of 14 years. Perphenazine, too, was dosed at the lower end of its range (mean modal dose 20.8 mg/d) compared with the old community standard of 36 to 64 mg/d.

Generally, a mean modal dosage of 20.1 mg/d for olanzapine is considered equivalent to ziprasidone, 160 mg; quetiapine, 800 mg; and risperidone, 6 mg. In CATIE phase 1, mean modal dosages were:

• ziprasidone, 112.8 mg/d (30% below 160 mg)
• quetiapine, 543.4 mg/d (32% below 800)
• risperidone, 3.9 mg/d (35% below 6 mg).

Olanzapine’s starting dosage of 7.5 mg/d was relatively higher than those of the other atypicals, which may have produced more-rapid onset of efficacy.

Switching. Another potential “advantage” for olanzapine was that 22% of subjects were taking it when they enrolled. By random assignment, 23% of patients who were taking olanzapine stayed on olanzapine and did not switch. By comparison:

• No patients assigned to ziprasidone were taking it before entering the trial.
• Only 5% of those taking quetiapine stayed on that drug after randomization.
• Few were receiving perphenazine before enrollment.

Switching antipsychotics may increase side effect risk or efficacy problems. For example, a patient switched from olanzapine or quetiapine to ziprasidone or perphenazine may experience insomnia during the transition, which may lead to tolerability complaints.

Metabolic side effects seen in this trial support past observations and reports that olanzapine is associated with higher risk for weight gain, hyperglycemia, and hyperlipidemia than other antipsychotics.¹⁵ Data on metabolic changes in CATIE patients taking olanzapine are being analyzed.

Hyperprolactinemia was most common with risperidone and practically nonexistent with other antipsychotics—even perphenazine. On the other hand, risperidone had the most favorable tolerability profile. This implies that elevated prolactin does not necessarily lead to antipsychotic discontinuation because of tolerability among patients with schizophrenia.

QTC interval and cataract data were benign across all antipsychotics. These findings appear to exonerate ziprasidone and quetiapine, respectively, which have been perceived as associated with these side effects.

Related resources

• Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study. www.catie.unc.edu/schizophrenia
• Schizophrenia Research Forum. NARSAD, The Mental Health Research Association.www.schizophreniaforum.org

Drug brand names

• Aripiprazole • Abilify
• Olanzapine • Zyprexa
• Perphenazine • Trilafon
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Disclosures

Dr Nasrallah receives grants/research support from AstraZeneca, Janssen Pharmaceutica, Eli Lilly & Co., and Pfizer. He is a consultant, advisory board member, and speaker for Abbott Laboratories, AstraZeneca, Janssen Pharmaceutica, Pfizer, and Shire Pharmaceuticals Group.

Investigators faced a dilemma while designing the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). More than 200 enrollees with chronic schizophrenia had pre-existing tardive dyskinesia (TD). Would it be ethical to give them the antipsychotic most likely to worsen their TD? Would exempting them from taking that drug influence the trial’s outcome?

This issue and others had to be resolved before the largest controlled study of “real world” schizophrenia could begin. Now that data are unfolding, groups with diverse agendas are debating CATIE’s methods and surprising results. This article describes how the trial’s design and findings could transform public policy and clinical practice.

poll here

Efficacy vs Effectiveness

The National Institute of Mental Health funded the prospective CATIE schizophrenia study to compare the effectiveness of atypical antipsychotics versus each other and versus a first-generation (typical) antipsychotic.

All approved atypicals have shown similar efficacy compared with placebo in short-term trials (usually 6 weeks).¹ The CATIE trial’s rationale is that short-term efficacy studies required for FDA approval may not necessarily reflect the drugs’ effectiveness in long-term schizophrenia management. Effectiveness measures take into account efficacy as well as safety, tolerability, and unpredictable patient behaviors in the real world.

CATIE’s ‘Real World’ Patients

CATIE investigators enrolled a community sample of chronic schizophrenia patients similar to those many psychiatrists see. Very liberal inclusion and exclusion criteria (Table 1) allowed enrollees to have a history of substance abuse, comorbid psychiatric or medical disorders, be receiving other medications, or show evidence of TD. Their schizophrenia ranged from minimal to severe.^2,3

The 1,493 patients who completed the study (Table 2) were enrolled at 57 outpatient treatment settings. One site’s 33 patients were eliminated from analysis because of doubts about the integrity of the data, leaving a total of 1,460 subjects.⁴

Table 1

Criteria for enrolling patients in the CATIE schizophrenia trial

Table 2

CATIE’s 1,460 ‘real world’ schizophrenia patients at trial entry

Medications. Before randomization, 28% of enrollees were not receiving antipsychotics. The remainder were receiving:

• olanzapine (22%)
• risperidone (19%)
• quetiapine (7%)
• ziprasidone (0%; approved after the trial began)
• any combination of olanzapine, risperidone, and quetiapine (7%)
• typical antipsychotics (16%).

Metabolic profile. These outpatients had a high rate of metabolic disorders: 42%—twice the rate in the general population—met criteria for metabolic syndrome,⁵ putting them at high risk to die of cardiovascular causes within 10 years.⁶ They had relatively poor physical health self-ratings and increased somatic preoccupation.⁷ Most worrisome, many were receiving no medications for their metabolic disorders, including 45% of those with diabetes, 89% with hyperlipidemia, and 62% with hypertension.⁸

Substance abuse. At enrollment, 40% of patients were abstinent from substance use, 22% were using substances without abuse or dependence, and 37% had substance abuse or dependence. Compared with nonusers, substance abusers tended to be male with more childhood problems, higher positive symptoms on the Positive and Negative Syndrome Scale (PANSS), and more likely to have had a recent illness exacerbation.⁹

Tardive dyskinesia. The 231 subjects who met criteria for probable TD¹⁰ were older than the overall sample with more years of antipsychotic treatment, especially with conventional neuroleptics and anticholinergics. Substance abuse was associated with TD, as were severity of psychopathology, extrapyramidal symptoms (EPS), and akathisia.¹¹

Violent behavior. A history of serious violent behavior was reported in:

• 5.4% of patients with high positive and low negative PANSS symptom scores
• 1.7% of patients with low positive and high negative PANSS symptom scores.

Consent. Patients’ capacity to give consent to participate in the study was assessed with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Psychosis severity (PANSS positive symptom scale) was not found to affect decision-making capacity, but negative symptoms and diminished working memory did.¹²

CATIE’s Unique Design

Defining effectiveness. CATIE was designed in three phases (Figure). Phase 1—discussed here—was a blinded, controlled comparison of four atypical antipsychotics and perphenazine. Results of phases 2 and 3 have yet to be published. The primary effectiveness endpoint, “all-cause discontinuation,” was defined as:

• lack of efficacy (patient was switched to another drug assigned at random)
• lack of tolerability (patient requested a drug change)
• safety problem (investigator initiated a switch)
• patient’s decision for any reason (often dropping out of the study).

The longer subjects stayed on the first antipsychotic they received, the more effective that drug was considered to be.

Figure CATIE schizophrenia trial design

* Phase 1A: participants with tardive dyskinesia (N=231) do not get randomized to perphenazine; phase 1B: participants who fail perphenazine will be randomized to an atypical (olanzapine, quetiapine, or risperidone) before eligibility for phase 2.
Source: Reference 2.Medications. Three atypicals—risperidone, olanzapine, and quetiapine—were approved for schizophrenia when the trial began in 1999. Recruitment ended in June 2003, the last subject completed the 18-month trial in December 2004, and data analysis began in January 2005. Ziprasidone was added to phase 1 after 40% of the sample had been enrolled, and aripiprazole was included as an option in the unblinded phase 3.

Perphenazine was chosen to represent typical antipsychotics because it has medium potency and less risk of EPS than high-potency drugs such as haloperidol and is associated with less weight gain than low-potency drugs such as thioridazine.

Dosing. Pharmaceutical manufacturers donated the antipsychotics and were invited to recommend their respective drugs’ starting dosages, dose increments, and maximum dosages. Olanzapine’s maker requested a higher starting dosage (7.5 mg/d instead of 5.0 mg/d) and a maximum dosage 50% higher than the FDA-approved range (30 mg/d instead of 20 mg/d). The others recommended the FDA-approved dosage ranges or less:

• quetiapine, 200 to 800 mg/d
• risperidone, 1.5 to 6 mg/d
• ziprasidone, 40 to 160 mg/d
• perphenazine, 8 to 32 mg/d.

The study team accepted their recommendations.

The medications were packaged in identical capsules. Quetiapine and ziprasidone were given twice daily because of product labeling; risperidone, olanzapine, and perphenazine were given once daily to one-half the patients assigned to them and twice daily to the others to prevent raters from guessing which drug a patient was receiving.

Tardive dyskinesia. For ethical reasons, the 231 patients with TD at enrollment were randomly assigned in phase 1 to atypicals but not to perphenazine because of the well-established link between typical antipsychotics and TD. This exception could have contributed to the closer-than-expected differences in EPS and perhaps in efficacy, given reports that TD patients have more negative symptoms and cognitive dysfunction.¹³ However, a statistical analysis took that into account.

CATIE’s Key Findings

Discontinuation. A disappointingly high discontinuation rate (74% overall) within a few months was the most important finding (Table 3). A recent effectiveness study with a design similar to the CATIE trial found a similarly high rate of all-cause discontinuation (70%) in patients with first-episode psychosis.¹⁴ Thus, patient-initiated drug discontinuation appears to be a core illness behavior from schizophrenia onset to chronic illness.

The high discontinuation rate shows that we need to modify our approach to schizophrenia, emphasizing full adherence to antipsychotic therapy from the onset of the illness.

Table 3

All-cause discontinuation rates in the CATIE trial

Effectiveness—measured as all-cause discontinuation or switching—was the primary outcome of phase 1. The unexpected finding that perphenazine and the atypicals had similar effectiveness could influence clinical practice. Insurers, for example, might consider promoting cheaper typical antipsychotics for first-line use. CATIE’s cost-effectiveness arm (Rosenheck et al, submitted for publication) will provide additional data on this issue.

Before rushing to use older antipsychotics as first-line treatments for schizophrenia, however, policymakers should consider three factors in the study design that could have enhanced perphenazine’s efficacy and safety profiles.

First, perphenazine was given at lower dosages (up to 32 mg/d) than “real world” clinicians used a decade ago (up to 64 mg/d). Thus, lower rates of serious side effects, especially TD, might have occurred in the study than in past clinical practice. Since atypical antipsychotics were approved, clinicians see far fewer psychiatric patients with pill-rolling tremors, rigid posture, or a shuffling gait, compared with 10 to 15 years ago when typical antipsychotics were widely used.

Second, perphenazine was associated with the highest EPS rate (17%), though its mean modal dosage (20.8 mg/d) is considered moderate. Discontinuation because of EPS was highest with perphenazine and lowest with quetiapine.

Third, excluding enrollees with TD from perphenazine may have increased perphenazine’s effectiveness, whereas including them in the atypicals groups may have reduced the atypicals’ effectiveness. TD patients are at increased risk to develop EPS; they had more-severe illness and a higher substance abuse rate among CATIE patients.¹¹ Even so, investigators did control for TD in the data analysis and found no significant difference between typical and atypical antipsychotics.

No ‘Winners’ or ‘Losers’

Effectiveness, tolerability, and safety findings for each antipsychotic are compared in Tables 4A and 4B. Careful review shows no clear “winners” or “losers;” each agent has weaknesses but also strengths that may benefit individual patients.

Efficacy. Olanzapine showed a relatively higher efficacy and lower discontinuation rate but also had the highest risk of adverse metabolic effects. Some have attributed its greater efficacy to its higher dosing compared with the other antipsychotics. Some also have argued that the antipsychotics that showed lower efficacy, such as quetiapine and ziprasidone, were underdosed in this chronic schizophrenia population with a mean duration of illness of 14 years. Perphenazine, too, was dosed at the lower end of its range (mean modal dose 20.8 mg/d) compared with the old community standard of 36 to 64 mg/d.

Generally, a mean modal dosage of 20.1 mg/d for olanzapine is considered equivalent to ziprasidone, 160 mg; quetiapine, 800 mg; and risperidone, 6 mg. In CATIE phase 1, mean modal dosages were:

• ziprasidone, 112.8 mg/d (30% below 160 mg)
• quetiapine, 543.4 mg/d (32% below 800)
• risperidone, 3.9 mg/d (35% below 6 mg).

Olanzapine’s starting dosage of 7.5 mg/d was relatively higher than those of the other atypicals, which may have produced more-rapid onset of efficacy.

Switching. Another potential “advantage” for olanzapine was that 22% of subjects were taking it when they enrolled. By random assignment, 23% of patients who were taking olanzapine stayed on olanzapine and did not switch. By comparison:

• No patients assigned to ziprasidone were taking it before entering the trial.
• Only 5% of those taking quetiapine stayed on that drug after randomization.
• Few were receiving perphenazine before enrollment.

Switching antipsychotics may increase side effect risk or efficacy problems. For example, a patient switched from olanzapine or quetiapine to ziprasidone or perphenazine may experience insomnia during the transition, which may lead to tolerability complaints.

Metabolic side effects seen in this trial support past observations and reports that olanzapine is associated with higher risk for weight gain, hyperglycemia, and hyperlipidemia than other antipsychotics.¹⁵ Data on metabolic changes in CATIE patients taking olanzapine are being analyzed.

Hyperprolactinemia was most common with risperidone and practically nonexistent with other antipsychotics—even perphenazine. On the other hand, risperidone had the most favorable tolerability profile. This implies that elevated prolactin does not necessarily lead to antipsychotic discontinuation because of tolerability among patients with schizophrenia.

QTC interval and cataract data were benign across all antipsychotics. These findings appear to exonerate ziprasidone and quetiapine, respectively, which have been perceived as associated with these side effects.

Related resources

• Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study. www.catie.unc.edu/schizophrenia
• Schizophrenia Research Forum. NARSAD, The Mental Health Research Association.www.schizophreniaforum.org

Drug brand names

• Aripiprazole • Abilify
• Olanzapine • Zyprexa
• Perphenazine • Trilafon
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Disclosures

Dr Nasrallah receives grants/research support from AstraZeneca, Janssen Pharmaceutica, Eli Lilly & Co., and Pfizer. He is a consultant, advisory board member, and speaker for Abbott Laboratories, AstraZeneca, Janssen Pharmaceutica, Pfizer, and Shire Pharmaceuticals Group.

John, age 16, is admitted to our inpatient psychiatric unit, complaining of “a 2-week constant headache” caused by “voices arguing in my head.” He has lived in Mexico with an uncle for 6 months but returned home last week for medical evaluation of his headaches.

His parents report that John developed normally until 3 years ago, when he gradually lost interest in his favorite activities and became socially withdrawn. He has not attended school in 2 years. He has no history of illicit drug use and is not taking prescription or over the-counter medications.

Complete physical examination, neurologic exam, and routine screening lab test results are normal. Thinking that a high lead content of cookware used in Mexico might be causing John’s symptoms, we order a lead level: result-0.2 mg/dL (

We diagnose schizophreniform disorder, but John’s parents refuse to accept this diagnosis. They repeatedly ask if we can do more to identify a medical cause of their son’s psychiatric symptoms.

As in John’s case, young patients or their parents may resist the diagnosis of a chronic mental illness such as schizophrenia. Understandably, they may be invested in trying to identify “medically treatable” causes. You can address their anxieties by showing them that you have systematically evaluated medical causes of psychosis.

We offer such a tool: an algorithm and tables to help you identify common and rare medical conditions that may cause or exacerbate psychotic symptoms in patients ages 3 to 18.

An evidence-based algorithm

Multiple factors—developmental, psychological, family, environmental, or medical—typically cause psychotic symptoms in a child or adolescent. Evaluating all possibilities is essential, but guidelines tend to minimize medical causes. American Academy of Child and Adolescent Psychiatry guidelines, for example, recommend that “all medical disorders (including general medical conditions and substance-induced disorders) are ruled out,”¹ but they do not specify which medical conditions to consider.

To supplement existing guidelines, we searched the literature and developed an evidence-based algorithm to help you systematically consider medical causes of pediatric psychotic symptoms. We excluded children age 2

How to use it. The algorithm walks you through a medical systems review. You begin with a complete history, then address six causes of psychotic symptoms: substance abuse, medication reactions, general medical conditions, unexplained somatic symptoms (such as from toxic environmental exposures), developmental and learning disabilities, and atypical presentations.

Don’t stop if you find one possible cause of psychotic symptoms; continue to the end of the algorithm. The more factors you identify, the greater your chance of finding a treatable cause that may ameliorate your patient’s symptoms.

To make the algorithm clinically useful, we listed conditions in order of decreasing probability of causing psychotic symptoms. For example, the first cause listed is substance-induced disorders,³ which are most common among adolescent patients. We also “triaged” medical conditions from common to rare (based on estimated prevalence of association with psychotic symptoms), listing rare causes only in cases of atypical presentation or treatment resistance.

Supporting tables. The following discussion summarizes data that support the algorithm and its tables:

• medications reported to cause psychosis (Table 1)
  
• medical conditions most likely to cause psychosis (Table 2)
  
• medical conditions that rarely cause psychosis (Table 3).
  

Drugs that may cause psychotic symptoms

Common medical conditions that may cause pediatric psychosis symptoms*

Medical conditions that rarely cause pediatric psychosis symptoms*

Substance abuse

Substance abuse is common among adolescents and adults with psychotic illnesses.⁴ Drug-induced states can cause delusions, hallucinations, paranoia, and disorganized behavior,⁵ which are reported most commonly during intoxication and withdrawal.⁶ Diagnosis is often straightforward because of the temporal association between the substance abuse and onset of psychotic symptoms.

Little evidence supports a causal relationship between drug use and the development of chronic psychotic symptoms, however. Case reports link use of 3,4-methylenedioxymethamphetamine (“Ecstasy”), lysergic acid diethylamide (LSD), and marijuana to chronic schizophrenia-like symptoms.⁷ The strongest evidence links long-term methamphetamine and cocaine use to chronic psychotic symptoms.^8,9

Medications

Side effects of at least 25 drug classes have been reported to mimic psychosis (Table 1),¹⁰ but little is known about the incidence and prevalence of this problem. Case reports and chart reviews provide the only data that associate most medications with psychotic symptoms. These disagree on what defines a “psychotic symptom,” and most fail to rule out delirium as a possible cause.

The relationship between glucocorticosteroids and psychotic symptoms has been studied extensively. A clear link has been found between corticosteroids at dosages >40 mg/d and a markedly elevated risk for transient psychotic symptoms.¹¹

Medical conditions

We identified 27 medical conditions that may cause or worsen clinical symptoms of psychosis (Tables 2 and 3) by searching PubMed, psychiatric journals, and neuropsychiatry and consult-liaison textbooks. We included only conditions:

• shown to cause significant morbidity in pediatric populations
  
• shown to have a statistically significant association with psychotic symptoms, or patients’ symptoms consistently resolved when the condition was treated.
  

Endocrine disorders. Behavioral disturbances (including psychosis) may be the earliest manifestation of an endocrine disorder.¹⁷ Cushing’s syndrome,¹⁸ hyperthyroidism,¹⁹ and hypothyroidism²⁰—met our inclusion criteria.

Cushing’s syndrome—caused by long-term systemic glucocorticoids and thyroid disorders—is not uncommon in children and adolescents but rarely presents with psychotic behaviors. For each endocrine disorder we included, however, at least one case report described delayed diagnosis because of prominent psychosis. Treating the endocrinopathies resolved the psychotic symptoms.

Genetic disorders. Genetically determined neurodevelopmental disorders usually present in very young children, but some may appear later. Genetic conditions that co-occur with psychotic symptoms at rates significantly greater than the population prevalence include Prader-Willi syndrome,²¹ metachromatic leukodystrophy,²² Turner’s syndrome,²¹ velocardiofacial syndrome,²³ and Wilson’s disease.¹⁵

Acute intermittent porphyria, GM₂ gangliosidosis (Tay-Sachs disease), and homocystinuria are rare conditions with unknown prevalence in patients with psychotic disorders. Still, they are important to consider when evaluating youths with psychosis because case reports link their treatment with psychotic symptom resolution.^24-26

Infectious disease. An infectious CNS disease does not usually present with psychotic symptoms only. When this does happen, making the correct diagnosis as soon as possible is critical because early treatment is associated with better outcomes.²⁷ Misdiagnosis as a primary psychotic disorder may expose a patient to psychotropics that may adversely affect clinical outcome.

Viruses that affect the CNS (viral encephalopathies) are the infections most likely to cause psychotic symptoms. By decreasing frequency, they are human simian virus, HIV, influenza, measles, Epstein-Barr virus, mumps, and rabies.^27,28 Bacterial infections that cause psychosis include mycoplasma pneumonia,²⁹ syphilis,³⁰ typhoid fever,³¹ and Lyme disease.³²

Brain tumor. Childhood brain tumors often present with behavioral symptoms associated with headache, vomiting, visual changes, and motor and cognitive symptoms. A CNS tumor rarely presents with isolated neuropsychiatric symptoms.³³ A few case reports describe intracranial tumors initially misdiagnosed as primary psychotic illness because of prominent psychotic symptoms.^34,35 In each case, these symptoms resolved with tumor resection.

A temporal relationship does not necessarily equate to a “causal” relationship, however. Tatter et al³⁶ describe a case of “reoccurrence” of manic symptoms initially thought to be caused by an arteriovenous malformation (AVM) 10 years after the AVM was successfully removed. The important point is that, although rarely, pediatric brain tumor can present with prominent psychotic symptoms.

Environmental toxin exposure may cause well-defined psychiatric syndromes,³⁷ although frank psychosis is uncommon at presentation. Most often, environmental toxins produce an encephalopathic process of which psychosis may be one symptom. A few toxic exposures—such as lead,³⁸ carbon monoxide,³⁹ and elemental mercury⁴⁰ —have presented with prominent psychotic symptoms without other encephalopathic symptoms.

Collagen vascular disease is associated with significantly elevated rates of psychiatric illness, especially depression, but only systemic lupus erythematosus (SLE) is known to be associated with prominent psychosis. Case series report delayed SLE diagnosis in patients with this presentation.⁴¹

High-dose pulse corticosteroids have been reported to effectively treat SLE-related psychotic symptoms,⁴² although high-dose corticosteroids can also cause psychotic symptoms. The timing and character of the symptoms can help you determine whether using corticosteroids is helping or making the patient worse.

Using the algorithm

John’s mother and father fear that the inpatient team’s diagnosis of a primary psychotic disorder means that a medical cause has been permanently “ruled out.” To reassure them, we use the algorithm to explain in concrete terms the thought process that led us to John’s psychiatric diagnosis. We walk them through the algorithm and its tables, explaining how we used evidence to rationally rule out all known medical causes of psychotic symptoms in pediatric patients.

John’s parents are relieved to know that the case is not closed, even though we found no medical cause for their son’s condition. If more clinical data become available, we remain open to considering the possibility that medical conditions could be causing or worsening their son’s symptoms.

Related resources

• American Academy of Child and Adolescent Psychiatry. Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 2001;40(7 Suppl):4S-23S.
  
• Schiffer RB, Klein RF, Sider RC. The medical evaluation of psychiatric patients. New York: Plenum Medical Book Co.; 1998.
  
• National Organization for Rare Disorders (NORD). www.rarediseases.org.
  

John, age 16, is admitted to our inpatient psychiatric unit, complaining of “a 2-week constant headache” caused by “voices arguing in my head.” He has lived in Mexico with an uncle for 6 months but returned home last week for medical evaluation of his headaches.

His parents report that John developed normally until 3 years ago, when he gradually lost interest in his favorite activities and became socially withdrawn. He has not attended school in 2 years. He has no history of illicit drug use and is not taking prescription or over the-counter medications.

Complete physical examination, neurologic exam, and routine screening lab test results are normal. Thinking that a high lead content of cookware used in Mexico might be causing John’s symptoms, we order a lead level: result-0.2 mg/dL (

We diagnose schizophreniform disorder, but John’s parents refuse to accept this diagnosis. They repeatedly ask if we can do more to identify a medical cause of their son’s psychiatric symptoms.

As in John’s case, young patients or their parents may resist the diagnosis of a chronic mental illness such as schizophrenia. Understandably, they may be invested in trying to identify “medically treatable” causes. You can address their anxieties by showing them that you have systematically evaluated medical causes of psychosis.

We offer such a tool: an algorithm and tables to help you identify common and rare medical conditions that may cause or exacerbate psychotic symptoms in patients ages 3 to 18.

An evidence-based algorithm

Multiple factors—developmental, psychological, family, environmental, or medical—typically cause psychotic symptoms in a child or adolescent. Evaluating all possibilities is essential, but guidelines tend to minimize medical causes. American Academy of Child and Adolescent Psychiatry guidelines, for example, recommend that “all medical disorders (including general medical conditions and substance-induced disorders) are ruled out,”¹ but they do not specify which medical conditions to consider.

To supplement existing guidelines, we searched the literature and developed an evidence-based algorithm to help you systematically consider medical causes of pediatric psychotic symptoms. We excluded children age 2

How to use it. The algorithm walks you through a medical systems review. You begin with a complete history, then address six causes of psychotic symptoms: substance abuse, medication reactions, general medical conditions, unexplained somatic symptoms (such as from toxic environmental exposures), developmental and learning disabilities, and atypical presentations.

Don’t stop if you find one possible cause of psychotic symptoms; continue to the end of the algorithm. The more factors you identify, the greater your chance of finding a treatable cause that may ameliorate your patient’s symptoms.

To make the algorithm clinically useful, we listed conditions in order of decreasing probability of causing psychotic symptoms. For example, the first cause listed is substance-induced disorders,³ which are most common among adolescent patients. We also “triaged” medical conditions from common to rare (based on estimated prevalence of association with psychotic symptoms), listing rare causes only in cases of atypical presentation or treatment resistance.

Supporting tables. The following discussion summarizes data that support the algorithm and its tables:

• medications reported to cause psychosis (Table 1)
  
• medical conditions most likely to cause psychosis (Table 2)
  
• medical conditions that rarely cause psychosis (Table 3).
  

Drugs that may cause psychotic symptoms

Common medical conditions that may cause pediatric psychosis symptoms*

Medical conditions that rarely cause pediatric psychosis symptoms*

Substance abuse

Substance abuse is common among adolescents and adults with psychotic illnesses.⁴ Drug-induced states can cause delusions, hallucinations, paranoia, and disorganized behavior,⁵ which are reported most commonly during intoxication and withdrawal.⁶ Diagnosis is often straightforward because of the temporal association between the substance abuse and onset of psychotic symptoms.

Little evidence supports a causal relationship between drug use and the development of chronic psychotic symptoms, however. Case reports link use of 3,4-methylenedioxymethamphetamine (“Ecstasy”), lysergic acid diethylamide (LSD), and marijuana to chronic schizophrenia-like symptoms.⁷ The strongest evidence links long-term methamphetamine and cocaine use to chronic psychotic symptoms.^8,9

Medications

Side effects of at least 25 drug classes have been reported to mimic psychosis (Table 1),¹⁰ but little is known about the incidence and prevalence of this problem. Case reports and chart reviews provide the only data that associate most medications with psychotic symptoms. These disagree on what defines a “psychotic symptom,” and most fail to rule out delirium as a possible cause.

The relationship between glucocorticosteroids and psychotic symptoms has been studied extensively. A clear link has been found between corticosteroids at dosages >40 mg/d and a markedly elevated risk for transient psychotic symptoms.¹¹

Medical conditions

We identified 27 medical conditions that may cause or worsen clinical symptoms of psychosis (Tables 2 and 3) by searching PubMed, psychiatric journals, and neuropsychiatry and consult-liaison textbooks. We included only conditions:

• shown to cause significant morbidity in pediatric populations
  
• shown to have a statistically significant association with psychotic symptoms, or patients’ symptoms consistently resolved when the condition was treated.
  

Endocrine disorders. Behavioral disturbances (including psychosis) may be the earliest manifestation of an endocrine disorder.¹⁷ Cushing’s syndrome,¹⁸ hyperthyroidism,¹⁹ and hypothyroidism²⁰—met our inclusion criteria.

Cushing’s syndrome—caused by long-term systemic glucocorticoids and thyroid disorders—is not uncommon in children and adolescents but rarely presents with psychotic behaviors. For each endocrine disorder we included, however, at least one case report described delayed diagnosis because of prominent psychosis. Treating the endocrinopathies resolved the psychotic symptoms.

Genetic disorders. Genetically determined neurodevelopmental disorders usually present in very young children, but some may appear later. Genetic conditions that co-occur with psychotic symptoms at rates significantly greater than the population prevalence include Prader-Willi syndrome,²¹ metachromatic leukodystrophy,²² Turner’s syndrome,²¹ velocardiofacial syndrome,²³ and Wilson’s disease.¹⁵

Acute intermittent porphyria, GM₂ gangliosidosis (Tay-Sachs disease), and homocystinuria are rare conditions with unknown prevalence in patients with psychotic disorders. Still, they are important to consider when evaluating youths with psychosis because case reports link their treatment with psychotic symptom resolution.^24-26

Infectious disease. An infectious CNS disease does not usually present with psychotic symptoms only. When this does happen, making the correct diagnosis as soon as possible is critical because early treatment is associated with better outcomes.²⁷ Misdiagnosis as a primary psychotic disorder may expose a patient to psychotropics that may adversely affect clinical outcome.

Viruses that affect the CNS (viral encephalopathies) are the infections most likely to cause psychotic symptoms. By decreasing frequency, they are human simian virus, HIV, influenza, measles, Epstein-Barr virus, mumps, and rabies.^27,28 Bacterial infections that cause psychosis include mycoplasma pneumonia,²⁹ syphilis,³⁰ typhoid fever,³¹ and Lyme disease.³²

Brain tumor. Childhood brain tumors often present with behavioral symptoms associated with headache, vomiting, visual changes, and motor and cognitive symptoms. A CNS tumor rarely presents with isolated neuropsychiatric symptoms.³³ A few case reports describe intracranial tumors initially misdiagnosed as primary psychotic illness because of prominent psychotic symptoms.^34,35 In each case, these symptoms resolved with tumor resection.

A temporal relationship does not necessarily equate to a “causal” relationship, however. Tatter et al³⁶ describe a case of “reoccurrence” of manic symptoms initially thought to be caused by an arteriovenous malformation (AVM) 10 years after the AVM was successfully removed. The important point is that, although rarely, pediatric brain tumor can present with prominent psychotic symptoms.

Environmental toxin exposure may cause well-defined psychiatric syndromes,³⁷ although frank psychosis is uncommon at presentation. Most often, environmental toxins produce an encephalopathic process of which psychosis may be one symptom. A few toxic exposures—such as lead,³⁸ carbon monoxide,³⁹ and elemental mercury⁴⁰ —have presented with prominent psychotic symptoms without other encephalopathic symptoms.

Collagen vascular disease is associated with significantly elevated rates of psychiatric illness, especially depression, but only systemic lupus erythematosus (SLE) is known to be associated with prominent psychosis. Case series report delayed SLE diagnosis in patients with this presentation.⁴¹

High-dose pulse corticosteroids have been reported to effectively treat SLE-related psychotic symptoms,⁴² although high-dose corticosteroids can also cause psychotic symptoms. The timing and character of the symptoms can help you determine whether using corticosteroids is helping or making the patient worse.

Using the algorithm

John’s mother and father fear that the inpatient team’s diagnosis of a primary psychotic disorder means that a medical cause has been permanently “ruled out.” To reassure them, we use the algorithm to explain in concrete terms the thought process that led us to John’s psychiatric diagnosis. We walk them through the algorithm and its tables, explaining how we used evidence to rationally rule out all known medical causes of psychotic symptoms in pediatric patients.

John’s parents are relieved to know that the case is not closed, even though we found no medical cause for their son’s condition. If more clinical data become available, we remain open to considering the possibility that medical conditions could be causing or worsening their son’s symptoms.

Related resources

• American Academy of Child and Adolescent Psychiatry. Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 2001;40(7 Suppl):4S-23S.
  
• Schiffer RB, Klein RF, Sider RC. The medical evaluation of psychiatric patients. New York: Plenum Medical Book Co.; 1998.
  
• National Organization for Rare Disorders (NORD). www.rarediseases.org.
  

John, age 16, is admitted to our inpatient psychiatric unit, complaining of “a 2-week constant headache” caused by “voices arguing in my head.” He has lived in Mexico with an uncle for 6 months but returned home last week for medical evaluation of his headaches.

His parents report that John developed normally until 3 years ago, when he gradually lost interest in his favorite activities and became socially withdrawn. He has not attended school in 2 years. He has no history of illicit drug use and is not taking prescription or over the-counter medications.

Complete physical examination, neurologic exam, and routine screening lab test results are normal. Thinking that a high lead content of cookware used in Mexico might be causing John’s symptoms, we order a lead level: result-0.2 mg/dL (

We diagnose schizophreniform disorder, but John’s parents refuse to accept this diagnosis. They repeatedly ask if we can do more to identify a medical cause of their son’s psychiatric symptoms.

As in John’s case, young patients or their parents may resist the diagnosis of a chronic mental illness such as schizophrenia. Understandably, they may be invested in trying to identify “medically treatable” causes. You can address their anxieties by showing them that you have systematically evaluated medical causes of psychosis.

We offer such a tool: an algorithm and tables to help you identify common and rare medical conditions that may cause or exacerbate psychotic symptoms in patients ages 3 to 18.

An evidence-based algorithm

Multiple factors—developmental, psychological, family, environmental, or medical—typically cause psychotic symptoms in a child or adolescent. Evaluating all possibilities is essential, but guidelines tend to minimize medical causes. American Academy of Child and Adolescent Psychiatry guidelines, for example, recommend that “all medical disorders (including general medical conditions and substance-induced disorders) are ruled out,”¹ but they do not specify which medical conditions to consider.

To supplement existing guidelines, we searched the literature and developed an evidence-based algorithm to help you systematically consider medical causes of pediatric psychotic symptoms. We excluded children age 2

How to use it. The algorithm walks you through a medical systems review. You begin with a complete history, then address six causes of psychotic symptoms: substance abuse, medication reactions, general medical conditions, unexplained somatic symptoms (such as from toxic environmental exposures), developmental and learning disabilities, and atypical presentations.

Don’t stop if you find one possible cause of psychotic symptoms; continue to the end of the algorithm. The more factors you identify, the greater your chance of finding a treatable cause that may ameliorate your patient’s symptoms.

To make the algorithm clinically useful, we listed conditions in order of decreasing probability of causing psychotic symptoms. For example, the first cause listed is substance-induced disorders,³ which are most common among adolescent patients. We also “triaged” medical conditions from common to rare (based on estimated prevalence of association with psychotic symptoms), listing rare causes only in cases of atypical presentation or treatment resistance.

Supporting tables. The following discussion summarizes data that support the algorithm and its tables:

• medications reported to cause psychosis (Table 1)
  
• medical conditions most likely to cause psychosis (Table 2)
  
• medical conditions that rarely cause psychosis (Table 3).
  

Drugs that may cause psychotic symptoms

Common medical conditions that may cause pediatric psychosis symptoms*

Medical conditions that rarely cause pediatric psychosis symptoms*

Substance abuse

Substance abuse is common among adolescents and adults with psychotic illnesses.⁴ Drug-induced states can cause delusions, hallucinations, paranoia, and disorganized behavior,⁵ which are reported most commonly during intoxication and withdrawal.⁶ Diagnosis is often straightforward because of the temporal association between the substance abuse and onset of psychotic symptoms.

Little evidence supports a causal relationship between drug use and the development of chronic psychotic symptoms, however. Case reports link use of 3,4-methylenedioxymethamphetamine (“Ecstasy”), lysergic acid diethylamide (LSD), and marijuana to chronic schizophrenia-like symptoms.⁷ The strongest evidence links long-term methamphetamine and cocaine use to chronic psychotic symptoms.^8,9

Medications

Side effects of at least 25 drug classes have been reported to mimic psychosis (Table 1),¹⁰ but little is known about the incidence and prevalence of this problem. Case reports and chart reviews provide the only data that associate most medications with psychotic symptoms. These disagree on what defines a “psychotic symptom,” and most fail to rule out delirium as a possible cause.

The relationship between glucocorticosteroids and psychotic symptoms has been studied extensively. A clear link has been found between corticosteroids at dosages >40 mg/d and a markedly elevated risk for transient psychotic symptoms.¹¹

Medical conditions

We identified 27 medical conditions that may cause or worsen clinical symptoms of psychosis (Tables 2 and 3) by searching PubMed, psychiatric journals, and neuropsychiatry and consult-liaison textbooks. We included only conditions:

• shown to cause significant morbidity in pediatric populations
  
• shown to have a statistically significant association with psychotic symptoms, or patients’ symptoms consistently resolved when the condition was treated.
  

Endocrine disorders. Behavioral disturbances (including psychosis) may be the earliest manifestation of an endocrine disorder.¹⁷ Cushing’s syndrome,¹⁸ hyperthyroidism,¹⁹ and hypothyroidism²⁰—met our inclusion criteria.

Cushing’s syndrome—caused by long-term systemic glucocorticoids and thyroid disorders—is not uncommon in children and adolescents but rarely presents with psychotic behaviors. For each endocrine disorder we included, however, at least one case report described delayed diagnosis because of prominent psychosis. Treating the endocrinopathies resolved the psychotic symptoms.

Genetic disorders. Genetically determined neurodevelopmental disorders usually present in very young children, but some may appear later. Genetic conditions that co-occur with psychotic symptoms at rates significantly greater than the population prevalence include Prader-Willi syndrome,²¹ metachromatic leukodystrophy,²² Turner’s syndrome,²¹ velocardiofacial syndrome,²³ and Wilson’s disease.¹⁵

Acute intermittent porphyria, GM₂ gangliosidosis (Tay-Sachs disease), and homocystinuria are rare conditions with unknown prevalence in patients with psychotic disorders. Still, they are important to consider when evaluating youths with psychosis because case reports link their treatment with psychotic symptom resolution.^24-26

Infectious disease. An infectious CNS disease does not usually present with psychotic symptoms only. When this does happen, making the correct diagnosis as soon as possible is critical because early treatment is associated with better outcomes.²⁷ Misdiagnosis as a primary psychotic disorder may expose a patient to psychotropics that may adversely affect clinical outcome.

Viruses that affect the CNS (viral encephalopathies) are the infections most likely to cause psychotic symptoms. By decreasing frequency, they are human simian virus, HIV, influenza, measles, Epstein-Barr virus, mumps, and rabies.^27,28 Bacterial infections that cause psychosis include mycoplasma pneumonia,²⁹ syphilis,³⁰ typhoid fever,³¹ and Lyme disease.³²

Brain tumor. Childhood brain tumors often present with behavioral symptoms associated with headache, vomiting, visual changes, and motor and cognitive symptoms. A CNS tumor rarely presents with isolated neuropsychiatric symptoms.³³ A few case reports describe intracranial tumors initially misdiagnosed as primary psychotic illness because of prominent psychotic symptoms.^34,35 In each case, these symptoms resolved with tumor resection.

A temporal relationship does not necessarily equate to a “causal” relationship, however. Tatter et al³⁶ describe a case of “reoccurrence” of manic symptoms initially thought to be caused by an arteriovenous malformation (AVM) 10 years after the AVM was successfully removed. The important point is that, although rarely, pediatric brain tumor can present with prominent psychotic symptoms.

Environmental toxin exposure may cause well-defined psychiatric syndromes,³⁷ although frank psychosis is uncommon at presentation. Most often, environmental toxins produce an encephalopathic process of which psychosis may be one symptom. A few toxic exposures—such as lead,³⁸ carbon monoxide,³⁹ and elemental mercury⁴⁰ —have presented with prominent psychotic symptoms without other encephalopathic symptoms.

Collagen vascular disease is associated with significantly elevated rates of psychiatric illness, especially depression, but only systemic lupus erythematosus (SLE) is known to be associated with prominent psychosis. Case series report delayed SLE diagnosis in patients with this presentation.⁴¹

High-dose pulse corticosteroids have been reported to effectively treat SLE-related psychotic symptoms,⁴² although high-dose corticosteroids can also cause psychotic symptoms. The timing and character of the symptoms can help you determine whether using corticosteroids is helping or making the patient worse.

Using the algorithm

John’s mother and father fear that the inpatient team’s diagnosis of a primary psychotic disorder means that a medical cause has been permanently “ruled out.” To reassure them, we use the algorithm to explain in concrete terms the thought process that led us to John’s psychiatric diagnosis. We walk them through the algorithm and its tables, explaining how we used evidence to rationally rule out all known medical causes of psychotic symptoms in pediatric patients.

John’s parents are relieved to know that the case is not closed, even though we found no medical cause for their son’s condition. If more clinical data become available, we remain open to considering the possibility that medical conditions could be causing or worsening their son’s symptoms.

Related resources

• American Academy of Child and Adolescent Psychiatry. Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 2001;40(7 Suppl):4S-23S.
  
• Schiffer RB, Klein RF, Sider RC. The medical evaluation of psychiatric patients. New York: Plenum Medical Book Co.; 1998.
  
• National Organization for Rare Disorders (NORD). www.rarediseases.org.
  

Do you make New Year’s resolutions? At least 60% of Americans do, according to a Kaiser Permanente “New Year’s and Health Issues Survey” of 1,000 U.S. adults. Rather depressingly, the survey also found that for every 10 respondents who kept their resolutions all year, 99 did not.

Going online to learn more, my Google search for “new year resolutions” yielded 1,360,000 results (by comparison, a search for “alien abduction” found 711,000). The U.S. government Web portal FirstGov.gov lists as the “most popular” resolutions: drink less alcohol, eat right, get a better education, get a better job, get fit, lose weight, quit smoking, reduce stress, save money, take a trip, and volunteer to help others.

Is it mentally healthy to make New Year’s resolutions? I suppose so, if they motivate you to make positive changes. For example, in this issue, Drs. Phil Bohnert and Anne O’Connell describe how to make changes in your life to prevent or recover from burnout. But the 10% New Year’s resolution “compliance rate” in the Kaiser Permanente survey suggests that fundamental lifestyle changes are uncommon, despite our good intentions.

If we make resolutions but don’t keep them, how could that be good? Maybe taking on health and moral issues once a year is countertherapeutic. Making resolutions, not keeping them, and then feeling guilty probably does more harm than good.

My resolution for 2005 was not to let anything drive me crazy during the year. That clearly proved overly ambitious. For 2006, I have resolved to try to watch more TV and to gain a few pounds. At least these resolutions should not leave me feeling guilty.

Best wishes for a healthy and happy new year from me and the Current Psychiatry family!

Do you make New Year’s resolutions? At least 60% of Americans do, according to a Kaiser Permanente “New Year’s and Health Issues Survey” of 1,000 U.S. adults. Rather depressingly, the survey also found that for every 10 respondents who kept their resolutions all year, 99 did not.

Going online to learn more, my Google search for “new year resolutions” yielded 1,360,000 results (by comparison, a search for “alien abduction” found 711,000). The U.S. government Web portal FirstGov.gov lists as the “most popular” resolutions: drink less alcohol, eat right, get a better education, get a better job, get fit, lose weight, quit smoking, reduce stress, save money, take a trip, and volunteer to help others.

Is it mentally healthy to make New Year’s resolutions? I suppose so, if they motivate you to make positive changes. For example, in this issue, Drs. Phil Bohnert and Anne O’Connell describe how to make changes in your life to prevent or recover from burnout. But the 10% New Year’s resolution “compliance rate” in the Kaiser Permanente survey suggests that fundamental lifestyle changes are uncommon, despite our good intentions.

If we make resolutions but don’t keep them, how could that be good? Maybe taking on health and moral issues once a year is countertherapeutic. Making resolutions, not keeping them, and then feeling guilty probably does more harm than good.

My resolution for 2005 was not to let anything drive me crazy during the year. That clearly proved overly ambitious. For 2006, I have resolved to try to watch more TV and to gain a few pounds. At least these resolutions should not leave me feeling guilty.

Best wishes for a healthy and happy new year from me and the Current Psychiatry family!

Do you make New Year’s resolutions? At least 60% of Americans do, according to a Kaiser Permanente “New Year’s and Health Issues Survey” of 1,000 U.S. adults. Rather depressingly, the survey also found that for every 10 respondents who kept their resolutions all year, 99 did not.

Going online to learn more, my Google search for “new year resolutions” yielded 1,360,000 results (by comparison, a search for “alien abduction” found 711,000). The U.S. government Web portal FirstGov.gov lists as the “most popular” resolutions: drink less alcohol, eat right, get a better education, get a better job, get fit, lose weight, quit smoking, reduce stress, save money, take a trip, and volunteer to help others.

Is it mentally healthy to make New Year’s resolutions? I suppose so, if they motivate you to make positive changes. For example, in this issue, Drs. Phil Bohnert and Anne O’Connell describe how to make changes in your life to prevent or recover from burnout. But the 10% New Year’s resolution “compliance rate” in the Kaiser Permanente survey suggests that fundamental lifestyle changes are uncommon, despite our good intentions.

If we make resolutions but don’t keep them, how could that be good? Maybe taking on health and moral issues once a year is countertherapeutic. Making resolutions, not keeping them, and then feeling guilty probably does more harm than good.

My resolution for 2005 was not to let anything drive me crazy during the year. That clearly proved overly ambitious. For 2006, I have resolved to try to watch more TV and to gain a few pounds. At least these resolutions should not leave me feeling guilty.

Best wishes for a healthy and happy new year from me and the Current Psychiatry family!