Current Psychiatry

Will this patient turn violent?” Psychiatrists face this tough question every day. Although predicting a complex behavior such as violence is nearly impossible, we can prepare for dangerous behavior and improve our safety by:

• knowing the risk factors for patient violence
  
• assessing individuals for violence potential before clinical encounters
  
• controlling situations to reduce injury risk.
  

In one study, more than 50% of psychiatrists and 75% of mental health nurses reported an act or threat of violence from patients within the past year.¹ To help you avoid becoming a statistic, this article provides a 5-step procedure (Box) to quickly assess and respond to risk of violence in a psychiatric patient.

Box

Step 1: Seek Patient History

A careful review of past events and those immediately preceding the clinical encounter is the best tool for assessing potential for violence. The more you can learn from the patient chart and other sources before you see the patient, the better (Table 1). Valuable clues can be obtained from interviews with family members, outpatient providers, police officers, and others who have had pertinent social contact with the patient.

Table 1

Will this patient become violent?
Questions to consider before a clinical encounter

A minority of patients account for most aggressive acts in clinical encounters. One study showed that recidivists committed 53% of all violent behaviors in a health care setting.⁴ A patient’s history of violence should be flagged in the chart and verbally passed on to staff to alert providers of increased risk.

However, not having a violent history does not guarantee that a patient will not become dangerous during a clinical encounter. All patients with a violent past had an initial violent episode, and that first time can occur in a practice setting.

Psychotic states by themselves appear to increase the risk of violence, although the literature is mixed.^5,6 Clearly, however, psychotic states associated with arousal or agitation do predispose patients to violence, especially if the psychosis involves active paranoid delusions or hallucinations associated with negative affect (anger, sadness, anxiety).⁷

Increased rates of violence have also been reported in psychiatric patients with:

• acute manic states associated with arousal or agitation⁸
  
• nonspecific neurologic abnormalities such as abnormal EEGs, localizing neurologic signs, or “soft signs” (impaired face-hand test, graphesthesia, stereognosis).⁹
  

Psychiatric diagnoses associated with increased risk of violence include schizophrenia, bipolar mania, alcohol and other substance abuse, and personality disorders.^11-13 In clinical practice, however, I find psychiatric diagnoses less useful in predicting violence than the patient’s arousal state and the other risk factors discussed above.

Step 2: Evaluate the Context

In addition to evidence-supported risk factors (Table 2), context—or the broader situation in which a patient is embedded at the time of psychiatric evaluation—plays a prominent role in potentially violent situations. For example, if “divorce” is listed as a presenting factor:

• Is the patient recently divorced, or did it occur years ago?
  
• Does he hate all women or just his ex-wife?
  
• Was she having an affair, and did he just learn about this?
  

Table 2

Risk factors for violence among psychiatric patients*

Step 3: Identify Arousal States

Patients rarely commit violent acts when their anxiety and moods are well controlled. They are more likely to become aggressive in high arousal states.

Fear is probably an element of most situations where patients act out violently. Because the fearful patient may not exhibit easily interpreted danger signals, however, you may unwittingly provoke an assault by violating his or her personal space. A fearful, paranoid patient requires a greater-than-usual “intimate zone,” although this need for increased space may not be obvious.

Minimize provocation by explaining your actions and behaviors in advance (such as, “I would like to enter the room, sit down, and talk with you for about 20 minutes”). Be businesslike with paranoid patients. Avoid exuding warmth, as they may view attempts at warmth as having sinister intent.

Clinicians are sometimes injured when trying to prevent a fearful, paranoid patient from fleeing. To avoid injury, don’t stand between the patient and the door. Let the patient escape from the immediate situation, and enlist security or police in further intervention attempts.

Anger is easy to recognize by signs of mounting tension. Loud voice, inappropriate staring, banging objects, clenched fists, agitated pacing, and verbal threats are common in the angry patient before a violent episode. Although this seems self-evident, it is surprising how many violent acts occur when these signs are obvious and noted by staff, yet no de-escalation measures are taken.

A patient’s verbal threats can actually help the clinician. This “red flag” alerts staff to focus on de-escalation techniques and prepare for a violent situation.

Confusion can be an underlying risk factor in patients with delirium or nonspecific organic brain syndrome. These patients may strike out unexpectedly when health care personnel are attempting to do routine procedures, and clinicians are sometimes caught off-guard when operating in a care-giving rather than defensive mode.

Clinicians can often avoid arousing confused patients by using orienting techniques and explaining their actions. For example, a nurse might say, “Hello Mr. X, I am a nurse and you are in this hospital for treatment of your illness. I will need to use this machine to check your blood pressure.”

Humiliation. Men in particular can react aggressively to loss of self-esteem and feelings of powerlessness. Take note if a man has been humiliated in front of family before being brought for evaluation; for example, was he removed by police in an emergency detention situation? This patient may need to act out violently to restore his sense of self.

Staff can lessen a patient’s potential to act on humiliation by using a therapeutic, esteem-building interview technique. For example, address the patient as “Mr.” instead of by first name, and highlight his strengths or accomplishments early in the interview.

Step 4: Structure the Interview for Safety

The time you take before an interview to learn about a patient’s violence history, context, and arousal state is time well-spent and more patient-specific than past diagnoses. This information allows you to prepare for a safe intervention.

Interview environment. The physical and social environment where you interview the patient may contribute to violence potential.

• Is the patient being interviewed in a cramped room or an open hallway?
  
• Is the evaluation unit overcrowded?
  
• Are security personnel visible?
  
• Is the examiner of the same race or ethnic background as the patient?
  

Take control of the interview and treatment situation. Use the physical space and personnel as you would any other intervention tool—to increase safety and decrease potential for violent behavior. For example, some patients do better when interviewed in a small, private setting. Other interviews must be conducted in a triage area while police escorts hold the patient and handcuffs remain on.

Ideally, you and the patient should have equal access to the door if you conduct the psychiatric interview in an enclosed room. With high-risk patients, arrange your seating at a 90-degree angle—rather than face-to-face-to limit sustained, confrontational eye contact. Sit at greater than an arm swing or leg kick away from the patient, and require him or her to remain seated during the interview (or you will promptly leave).

In the outpatient practice, terminate the interview or evaluation session if a patient in a negative affective arousal state does not allow verbal redirection. Before you make any movement to exit, however, announce, “I am leaving the room now.”

Trust your intuition. I do not enter a closed, private space with a patient unless I feel safe. If I feel afraid, I take that as a valuable warning that further safety measures are necessary.

Use restraints as needed. When patients with a history of violence are brought to the hospital in high arousal states, I let them remain in restraint with security present during the initial interview. If the patient cannot have a back-and-forth conversation with me, I keep the security force present until I believe my verbal interactions have a substantial effect.

Patients must be responsive to talking interventions before restraint, security, or other environmental safety measures are removed. Some patients do not reach this point until after tranquilizing medications are given.

Step 5: The Clinical Encounter

When discussing how to assess the likelihood of patient violence during a clinical encounter, a psychiatric colleague once commented, “Risk factors make you worry more; nothing makes you worry less.”

In other words, keep your guard up. Let clinical judgment take precedence over statistics when you are evaluating any patient. Statistics represent frequencies or averages; they may or may not apply to any one individual.

Techniques for assessing and treating violent patients are beyond the scope of this article, but at the very least:

• obtain training in safety/treatment protocols for violent patients
  
• ensure that your hospital/clinic has procedures in place to improve safety and to handle violent situations.
  

For every violent act that requires staff intervention, automatically schedule a debriefing session for those involved to assess the incident and allow them to express their feelings.

Related resources

• American Association for Emergency Psychiatry. www.emergencypsychiatry.org.
  
• Volavka J. The neurobiology of violence: an update. J Neuropsychiatry Clin Neurosci 1999;11:307-14.
  
• McNiel DE, Eisner JP, Binder RL. The relationship between command hallucinations and violence. Psychiatr Serv 2000;51: 1288-92.
  

Will this patient turn violent?” Psychiatrists face this tough question every day. Although predicting a complex behavior such as violence is nearly impossible, we can prepare for dangerous behavior and improve our safety by:

• knowing the risk factors for patient violence
  
• assessing individuals for violence potential before clinical encounters
  
• controlling situations to reduce injury risk.
  

In one study, more than 50% of psychiatrists and 75% of mental health nurses reported an act or threat of violence from patients within the past year.¹ To help you avoid becoming a statistic, this article provides a 5-step procedure (Box) to quickly assess and respond to risk of violence in a psychiatric patient.

Box

Step 1: Seek Patient History

A careful review of past events and those immediately preceding the clinical encounter is the best tool for assessing potential for violence. The more you can learn from the patient chart and other sources before you see the patient, the better (Table 1). Valuable clues can be obtained from interviews with family members, outpatient providers, police officers, and others who have had pertinent social contact with the patient.

Table 1

Will this patient become violent?
Questions to consider before a clinical encounter

A minority of patients account for most aggressive acts in clinical encounters. One study showed that recidivists committed 53% of all violent behaviors in a health care setting.⁴ A patient’s history of violence should be flagged in the chart and verbally passed on to staff to alert providers of increased risk.

However, not having a violent history does not guarantee that a patient will not become dangerous during a clinical encounter. All patients with a violent past had an initial violent episode, and that first time can occur in a practice setting.

Psychotic states by themselves appear to increase the risk of violence, although the literature is mixed.^5,6 Clearly, however, psychotic states associated with arousal or agitation do predispose patients to violence, especially if the psychosis involves active paranoid delusions or hallucinations associated with negative affect (anger, sadness, anxiety).⁷

Increased rates of violence have also been reported in psychiatric patients with:

• acute manic states associated with arousal or agitation⁸
  
• nonspecific neurologic abnormalities such as abnormal EEGs, localizing neurologic signs, or “soft signs” (impaired face-hand test, graphesthesia, stereognosis).⁹
  

Psychiatric diagnoses associated with increased risk of violence include schizophrenia, bipolar mania, alcohol and other substance abuse, and personality disorders.^11-13 In clinical practice, however, I find psychiatric diagnoses less useful in predicting violence than the patient’s arousal state and the other risk factors discussed above.

Step 2: Evaluate the Context

In addition to evidence-supported risk factors (Table 2), context—or the broader situation in which a patient is embedded at the time of psychiatric evaluation—plays a prominent role in potentially violent situations. For example, if “divorce” is listed as a presenting factor:

• Is the patient recently divorced, or did it occur years ago?
  
• Does he hate all women or just his ex-wife?
  
• Was she having an affair, and did he just learn about this?
  

Table 2

Risk factors for violence among psychiatric patients*

Step 3: Identify Arousal States

Patients rarely commit violent acts when their anxiety and moods are well controlled. They are more likely to become aggressive in high arousal states.

Fear is probably an element of most situations where patients act out violently. Because the fearful patient may not exhibit easily interpreted danger signals, however, you may unwittingly provoke an assault by violating his or her personal space. A fearful, paranoid patient requires a greater-than-usual “intimate zone,” although this need for increased space may not be obvious.

Minimize provocation by explaining your actions and behaviors in advance (such as, “I would like to enter the room, sit down, and talk with you for about 20 minutes”). Be businesslike with paranoid patients. Avoid exuding warmth, as they may view attempts at warmth as having sinister intent.

Clinicians are sometimes injured when trying to prevent a fearful, paranoid patient from fleeing. To avoid injury, don’t stand between the patient and the door. Let the patient escape from the immediate situation, and enlist security or police in further intervention attempts.

Anger is easy to recognize by signs of mounting tension. Loud voice, inappropriate staring, banging objects, clenched fists, agitated pacing, and verbal threats are common in the angry patient before a violent episode. Although this seems self-evident, it is surprising how many violent acts occur when these signs are obvious and noted by staff, yet no de-escalation measures are taken.

A patient’s verbal threats can actually help the clinician. This “red flag” alerts staff to focus on de-escalation techniques and prepare for a violent situation.

Confusion can be an underlying risk factor in patients with delirium or nonspecific organic brain syndrome. These patients may strike out unexpectedly when health care personnel are attempting to do routine procedures, and clinicians are sometimes caught off-guard when operating in a care-giving rather than defensive mode.

Clinicians can often avoid arousing confused patients by using orienting techniques and explaining their actions. For example, a nurse might say, “Hello Mr. X, I am a nurse and you are in this hospital for treatment of your illness. I will need to use this machine to check your blood pressure.”

Humiliation. Men in particular can react aggressively to loss of self-esteem and feelings of powerlessness. Take note if a man has been humiliated in front of family before being brought for evaluation; for example, was he removed by police in an emergency detention situation? This patient may need to act out violently to restore his sense of self.

Staff can lessen a patient’s potential to act on humiliation by using a therapeutic, esteem-building interview technique. For example, address the patient as “Mr.” instead of by first name, and highlight his strengths or accomplishments early in the interview.

Step 4: Structure the Interview for Safety

The time you take before an interview to learn about a patient’s violence history, context, and arousal state is time well-spent and more patient-specific than past diagnoses. This information allows you to prepare for a safe intervention.

Interview environment. The physical and social environment where you interview the patient may contribute to violence potential.

• Is the patient being interviewed in a cramped room or an open hallway?
  
• Is the evaluation unit overcrowded?
  
• Are security personnel visible?
  
• Is the examiner of the same race or ethnic background as the patient?
  

Take control of the interview and treatment situation. Use the physical space and personnel as you would any other intervention tool—to increase safety and decrease potential for violent behavior. For example, some patients do better when interviewed in a small, private setting. Other interviews must be conducted in a triage area while police escorts hold the patient and handcuffs remain on.

Ideally, you and the patient should have equal access to the door if you conduct the psychiatric interview in an enclosed room. With high-risk patients, arrange your seating at a 90-degree angle—rather than face-to-face-to limit sustained, confrontational eye contact. Sit at greater than an arm swing or leg kick away from the patient, and require him or her to remain seated during the interview (or you will promptly leave).

In the outpatient practice, terminate the interview or evaluation session if a patient in a negative affective arousal state does not allow verbal redirection. Before you make any movement to exit, however, announce, “I am leaving the room now.”

Trust your intuition. I do not enter a closed, private space with a patient unless I feel safe. If I feel afraid, I take that as a valuable warning that further safety measures are necessary.

Use restraints as needed. When patients with a history of violence are brought to the hospital in high arousal states, I let them remain in restraint with security present during the initial interview. If the patient cannot have a back-and-forth conversation with me, I keep the security force present until I believe my verbal interactions have a substantial effect.

Patients must be responsive to talking interventions before restraint, security, or other environmental safety measures are removed. Some patients do not reach this point until after tranquilizing medications are given.

Step 5: The Clinical Encounter

When discussing how to assess the likelihood of patient violence during a clinical encounter, a psychiatric colleague once commented, “Risk factors make you worry more; nothing makes you worry less.”

In other words, keep your guard up. Let clinical judgment take precedence over statistics when you are evaluating any patient. Statistics represent frequencies or averages; they may or may not apply to any one individual.

Techniques for assessing and treating violent patients are beyond the scope of this article, but at the very least:

• obtain training in safety/treatment protocols for violent patients
  
• ensure that your hospital/clinic has procedures in place to improve safety and to handle violent situations.
  

For every violent act that requires staff intervention, automatically schedule a debriefing session for those involved to assess the incident and allow them to express their feelings.

Related resources

• American Association for Emergency Psychiatry. www.emergencypsychiatry.org.
  
• Volavka J. The neurobiology of violence: an update. J Neuropsychiatry Clin Neurosci 1999;11:307-14.
  
• McNiel DE, Eisner JP, Binder RL. The relationship between command hallucinations and violence. Psychiatr Serv 2000;51: 1288-92.
  

Will this patient turn violent?” Psychiatrists face this tough question every day. Although predicting a complex behavior such as violence is nearly impossible, we can prepare for dangerous behavior and improve our safety by:

• knowing the risk factors for patient violence
  
• assessing individuals for violence potential before clinical encounters
  
• controlling situations to reduce injury risk.
  

In one study, more than 50% of psychiatrists and 75% of mental health nurses reported an act or threat of violence from patients within the past year.¹ To help you avoid becoming a statistic, this article provides a 5-step procedure (Box) to quickly assess and respond to risk of violence in a psychiatric patient.

Box

Step 1: Seek Patient History

A careful review of past events and those immediately preceding the clinical encounter is the best tool for assessing potential for violence. The more you can learn from the patient chart and other sources before you see the patient, the better (Table 1). Valuable clues can be obtained from interviews with family members, outpatient providers, police officers, and others who have had pertinent social contact with the patient.

Table 1

Will this patient become violent?
Questions to consider before a clinical encounter

A minority of patients account for most aggressive acts in clinical encounters. One study showed that recidivists committed 53% of all violent behaviors in a health care setting.⁴ A patient’s history of violence should be flagged in the chart and verbally passed on to staff to alert providers of increased risk.

However, not having a violent history does not guarantee that a patient will not become dangerous during a clinical encounter. All patients with a violent past had an initial violent episode, and that first time can occur in a practice setting.

Psychotic states by themselves appear to increase the risk of violence, although the literature is mixed.^5,6 Clearly, however, psychotic states associated with arousal or agitation do predispose patients to violence, especially if the psychosis involves active paranoid delusions or hallucinations associated with negative affect (anger, sadness, anxiety).⁷

Increased rates of violence have also been reported in psychiatric patients with:

• acute manic states associated with arousal or agitation⁸
  
• nonspecific neurologic abnormalities such as abnormal EEGs, localizing neurologic signs, or “soft signs” (impaired face-hand test, graphesthesia, stereognosis).⁹
  

Psychiatric diagnoses associated with increased risk of violence include schizophrenia, bipolar mania, alcohol and other substance abuse, and personality disorders.^11-13 In clinical practice, however, I find psychiatric diagnoses less useful in predicting violence than the patient’s arousal state and the other risk factors discussed above.

Step 2: Evaluate the Context

In addition to evidence-supported risk factors (Table 2), context—or the broader situation in which a patient is embedded at the time of psychiatric evaluation—plays a prominent role in potentially violent situations. For example, if “divorce” is listed as a presenting factor:

• Is the patient recently divorced, or did it occur years ago?
  
• Does he hate all women or just his ex-wife?
  
• Was she having an affair, and did he just learn about this?
  

Table 2

Risk factors for violence among psychiatric patients*

Step 3: Identify Arousal States

Patients rarely commit violent acts when their anxiety and moods are well controlled. They are more likely to become aggressive in high arousal states.

Fear is probably an element of most situations where patients act out violently. Because the fearful patient may not exhibit easily interpreted danger signals, however, you may unwittingly provoke an assault by violating his or her personal space. A fearful, paranoid patient requires a greater-than-usual “intimate zone,” although this need for increased space may not be obvious.

Minimize provocation by explaining your actions and behaviors in advance (such as, “I would like to enter the room, sit down, and talk with you for about 20 minutes”). Be businesslike with paranoid patients. Avoid exuding warmth, as they may view attempts at warmth as having sinister intent.

Clinicians are sometimes injured when trying to prevent a fearful, paranoid patient from fleeing. To avoid injury, don’t stand between the patient and the door. Let the patient escape from the immediate situation, and enlist security or police in further intervention attempts.

Anger is easy to recognize by signs of mounting tension. Loud voice, inappropriate staring, banging objects, clenched fists, agitated pacing, and verbal threats are common in the angry patient before a violent episode. Although this seems self-evident, it is surprising how many violent acts occur when these signs are obvious and noted by staff, yet no de-escalation measures are taken.

A patient’s verbal threats can actually help the clinician. This “red flag” alerts staff to focus on de-escalation techniques and prepare for a violent situation.

Confusion can be an underlying risk factor in patients with delirium or nonspecific organic brain syndrome. These patients may strike out unexpectedly when health care personnel are attempting to do routine procedures, and clinicians are sometimes caught off-guard when operating in a care-giving rather than defensive mode.

Clinicians can often avoid arousing confused patients by using orienting techniques and explaining their actions. For example, a nurse might say, “Hello Mr. X, I am a nurse and you are in this hospital for treatment of your illness. I will need to use this machine to check your blood pressure.”

Humiliation. Men in particular can react aggressively to loss of self-esteem and feelings of powerlessness. Take note if a man has been humiliated in front of family before being brought for evaluation; for example, was he removed by police in an emergency detention situation? This patient may need to act out violently to restore his sense of self.

Staff can lessen a patient’s potential to act on humiliation by using a therapeutic, esteem-building interview technique. For example, address the patient as “Mr.” instead of by first name, and highlight his strengths or accomplishments early in the interview.

Step 4: Structure the Interview for Safety

The time you take before an interview to learn about a patient’s violence history, context, and arousal state is time well-spent and more patient-specific than past diagnoses. This information allows you to prepare for a safe intervention.

Interview environment. The physical and social environment where you interview the patient may contribute to violence potential.

• Is the patient being interviewed in a cramped room or an open hallway?
  
• Is the evaluation unit overcrowded?
  
• Are security personnel visible?
  
• Is the examiner of the same race or ethnic background as the patient?
  

Take control of the interview and treatment situation. Use the physical space and personnel as you would any other intervention tool—to increase safety and decrease potential for violent behavior. For example, some patients do better when interviewed in a small, private setting. Other interviews must be conducted in a triage area while police escorts hold the patient and handcuffs remain on.

Ideally, you and the patient should have equal access to the door if you conduct the psychiatric interview in an enclosed room. With high-risk patients, arrange your seating at a 90-degree angle—rather than face-to-face-to limit sustained, confrontational eye contact. Sit at greater than an arm swing or leg kick away from the patient, and require him or her to remain seated during the interview (or you will promptly leave).

In the outpatient practice, terminate the interview or evaluation session if a patient in a negative affective arousal state does not allow verbal redirection. Before you make any movement to exit, however, announce, “I am leaving the room now.”

Trust your intuition. I do not enter a closed, private space with a patient unless I feel safe. If I feel afraid, I take that as a valuable warning that further safety measures are necessary.

Use restraints as needed. When patients with a history of violence are brought to the hospital in high arousal states, I let them remain in restraint with security present during the initial interview. If the patient cannot have a back-and-forth conversation with me, I keep the security force present until I believe my verbal interactions have a substantial effect.

Patients must be responsive to talking interventions before restraint, security, or other environmental safety measures are removed. Some patients do not reach this point until after tranquilizing medications are given.

Step 5: The Clinical Encounter

When discussing how to assess the likelihood of patient violence during a clinical encounter, a psychiatric colleague once commented, “Risk factors make you worry more; nothing makes you worry less.”

In other words, keep your guard up. Let clinical judgment take precedence over statistics when you are evaluating any patient. Statistics represent frequencies or averages; they may or may not apply to any one individual.

Techniques for assessing and treating violent patients are beyond the scope of this article, but at the very least:

• obtain training in safety/treatment protocols for violent patients
  
• ensure that your hospital/clinic has procedures in place to improve safety and to handle violent situations.
  

For every violent act that requires staff intervention, automatically schedule a debriefing session for those involved to assess the incident and allow them to express their feelings.

Related resources

• American Association for Emergency Psychiatry. www.emergencypsychiatry.org.
  
• Volavka J. The neurobiology of violence: an update. J Neuropsychiatry Clin Neurosci 1999;11:307-14.
  
• McNiel DE, Eisner JP, Binder RL. The relationship between command hallucinations and violence. Psychiatr Serv 2000;51: 1288-92.
  

Energy drinks’ popularity has soared among consumers who crave an energy boost from the highly caffeinated herbal concoctions. Clinicians should ask patients about energy drink consumption because:

• caffeine abuse can exacerbate mood and anxiety disorders and disrupt sleep patterns
  
• herbal additives can cause physical and/or psychiatric side effects
  
• some ingredients interact with prescription or OTC medications
  
• effects of energy drinks may contribute to a patient’s presenting complaint.
  

Approximately 70% of patients¹ do not report energy drink use because they believe these products are natural and safe. Ask patients if they consume energy drinks so you can alert them to the health risks.

A Stimulating recipe

Two main ingredients in most energy drinks are caffeine and carbohydrates in the form of glucose, sucrose, fructose, galactose, and maltodextrins (Table).

Table

Caffeine and carbohydrate content of popular energy drinks

Caffeine. Energy drinks contain 75 to 158 mg of caffeine per can—8 ounces of coffee has 150 mg of caffeine. Also, some products include the South American plant extracts guarana or yerba mate, which contain an unknown amount of caffeine.

High caffeine intake—≥300 mg/d—might exacerbate bipolar disorder’s manic symptoms. Also find out about additional caffeine intake from coffee, tea, soda, and some OTC medications, such as Excedrin.

Herbal ingredients. Ginseng or ginkgo biloba can cause patients to feel jittery or anxious. When taken in large amounts—the FDA has no guidelines on safe dosages—these ingredients can aggravate manic or psychotic symptoms.

Significant energy drink consumption—3 or more 8-oz drinks per day—can bring about physical side effects such as tachycardia and insomnia. Advise patients to limit their intake to 2 drinks per day, and suggest safer ways to increase energy levels such as moderate exercise and adequate sleep.

Energy drinks’ popularity has soared among consumers who crave an energy boost from the highly caffeinated herbal concoctions. Clinicians should ask patients about energy drink consumption because:

• caffeine abuse can exacerbate mood and anxiety disorders and disrupt sleep patterns
  
• herbal additives can cause physical and/or psychiatric side effects
  
• some ingredients interact with prescription or OTC medications
  
• effects of energy drinks may contribute to a patient’s presenting complaint.
  

Approximately 70% of patients¹ do not report energy drink use because they believe these products are natural and safe. Ask patients if they consume energy drinks so you can alert them to the health risks.

A Stimulating recipe

Two main ingredients in most energy drinks are caffeine and carbohydrates in the form of glucose, sucrose, fructose, galactose, and maltodextrins (Table).

Table

Caffeine and carbohydrate content of popular energy drinks

Caffeine. Energy drinks contain 75 to 158 mg of caffeine per can—8 ounces of coffee has 150 mg of caffeine. Also, some products include the South American plant extracts guarana or yerba mate, which contain an unknown amount of caffeine.

High caffeine intake—≥300 mg/d—might exacerbate bipolar disorder’s manic symptoms. Also find out about additional caffeine intake from coffee, tea, soda, and some OTC medications, such as Excedrin.

Herbal ingredients. Ginseng or ginkgo biloba can cause patients to feel jittery or anxious. When taken in large amounts—the FDA has no guidelines on safe dosages—these ingredients can aggravate manic or psychotic symptoms.

Significant energy drink consumption—3 or more 8-oz drinks per day—can bring about physical side effects such as tachycardia and insomnia. Advise patients to limit their intake to 2 drinks per day, and suggest safer ways to increase energy levels such as moderate exercise and adequate sleep.

Energy drinks’ popularity has soared among consumers who crave an energy boost from the highly caffeinated herbal concoctions. Clinicians should ask patients about energy drink consumption because:

• caffeine abuse can exacerbate mood and anxiety disorders and disrupt sleep patterns
  
• herbal additives can cause physical and/or psychiatric side effects
  
• some ingredients interact with prescription or OTC medications
  
• effects of energy drinks may contribute to a patient’s presenting complaint.
  

Approximately 70% of patients¹ do not report energy drink use because they believe these products are natural and safe. Ask patients if they consume energy drinks so you can alert them to the health risks.

A Stimulating recipe

Two main ingredients in most energy drinks are caffeine and carbohydrates in the form of glucose, sucrose, fructose, galactose, and maltodextrins (Table).

Table

Caffeine and carbohydrate content of popular energy drinks

Caffeine. Energy drinks contain 75 to 158 mg of caffeine per can—8 ounces of coffee has 150 mg of caffeine. Also, some products include the South American plant extracts guarana or yerba mate, which contain an unknown amount of caffeine.

High caffeine intake—≥300 mg/d—might exacerbate bipolar disorder’s manic symptoms. Also find out about additional caffeine intake from coffee, tea, soda, and some OTC medications, such as Excedrin.

Herbal ingredients. Ginseng or ginkgo biloba can cause patients to feel jittery or anxious. When taken in large amounts—the FDA has no guidelines on safe dosages—these ingredients can aggravate manic or psychotic symptoms.

Significant energy drink consumption—3 or more 8-oz drinks per day—can bring about physical side effects such as tachycardia and insomnia. Advise patients to limit their intake to 2 drinks per day, and suggest safer ways to increase energy levels such as moderate exercise and adequate sleep.

A consultation-liaison psychiatrist is called in to help manage “schizophrenia” in a middle-aged attorney who is recovering from a complicated cardiac bypass procedure. This patient is not mentally ill, the psychiatrist realizes, but has delirium with rapid-onset neuropsychiatric symptoms noted by fluctuations in arousal and associated changes in sleep, mood, personality, and cognition. This example illustrates 1 of 10 myths about delirium:

1. My patient is paranoid, therefore he or she must be schizophrenic

Patients with delirium may present with perceptual disturbances such as hallucinations, delusions, or paranoia. An otherwise highly functioning individual with symptom onset while in a medical setting likely has delirium, not a chronic mental disorder such as schizophrenia.

2. Delirium is rare

Delirium is found frequently in medically ill populations. In some groups, such as stem-cell transplant patients, rates may approach 50%. Risk factors include medical severity and advanced patient age.¹

3. Delirium is not serious

Delirium is associated with increased morbidity and mortality. It is a marker for “cerebral insufficiency”—reversible impairment in brain function—and requires prompt treatment.^2-4

4. Sleep deprivation causes delirium

Disrupted sleep in hospitalized patients—otherwise known as “ICU psychosis”—is more likely the result of delirium than the cause. Patients’ delirium and sleep both improve when they move from the ICU to a general medical floor, a reflection of their improved medical condition.⁵

5. Delirium goes away rapidly

Delirium usually lasts for days or weeks. Many patients—although superficially improved—still have subtle cognitive deficits and difficulty with daily activities.

6. The patient’s medical problem has been treated, so the delirium should resolve

A patient’s CNS often needs time to recover, and delirium may persist after the underlying medical cause has been treated. Delirium can be caused by factors other than medical illness, such as sedating, analgesic, or antiemetic medications.

7. My delirious patient cannot make medical decisions

Many patients with delirium can make decisions during more lucid periods. As their delirium improves, they should be able to participate in decision-making.

8. My patient cannot be delirious because he or she is oriented to time and place

Simple orientation questions can miss subtle signs of delirium. Watch for an inability to function cognitively at the individual’s baseline level. For example, a software engineer who is unable to draw a clock could be delirious.

9. My patient has depression, not delirium, because he or she is not getting out of bed

Delirium can present with changes of mood, energy, and personality that mimic depression. Even severely depressed individuals can function at a basic cognitive level and maintain daytime wakefulness, whereas patients with delirium may not.

10. Delirium cannot be treated

Manage delirium by evaluating and treating underlying medical precipitants such as metabolic derangement, infection, dehydration, hypoxia, pain, or medication effects. Also consider CNS injuries including stroke, head injury, or neoplasm. Research suggests antipsychotic medications at low dosages^6,7 can safely treat delirium. Improving orientation and comfort by reassuring the patient, assessing for anxiety, and reducing excessive noise and stimulation also help.

A consultation-liaison psychiatrist is called in to help manage “schizophrenia” in a middle-aged attorney who is recovering from a complicated cardiac bypass procedure. This patient is not mentally ill, the psychiatrist realizes, but has delirium with rapid-onset neuropsychiatric symptoms noted by fluctuations in arousal and associated changes in sleep, mood, personality, and cognition. This example illustrates 1 of 10 myths about delirium:

1. My patient is paranoid, therefore he or she must be schizophrenic

Patients with delirium may present with perceptual disturbances such as hallucinations, delusions, or paranoia. An otherwise highly functioning individual with symptom onset while in a medical setting likely has delirium, not a chronic mental disorder such as schizophrenia.

2. Delirium is rare

Delirium is found frequently in medically ill populations. In some groups, such as stem-cell transplant patients, rates may approach 50%. Risk factors include medical severity and advanced patient age.¹

3. Delirium is not serious

Delirium is associated with increased morbidity and mortality. It is a marker for “cerebral insufficiency”—reversible impairment in brain function—and requires prompt treatment.^2-4

4. Sleep deprivation causes delirium

Disrupted sleep in hospitalized patients—otherwise known as “ICU psychosis”—is more likely the result of delirium than the cause. Patients’ delirium and sleep both improve when they move from the ICU to a general medical floor, a reflection of their improved medical condition.⁵

5. Delirium goes away rapidly

Delirium usually lasts for days or weeks. Many patients—although superficially improved—still have subtle cognitive deficits and difficulty with daily activities.

6. The patient’s medical problem has been treated, so the delirium should resolve

A patient’s CNS often needs time to recover, and delirium may persist after the underlying medical cause has been treated. Delirium can be caused by factors other than medical illness, such as sedating, analgesic, or antiemetic medications.

7. My delirious patient cannot make medical decisions

Many patients with delirium can make decisions during more lucid periods. As their delirium improves, they should be able to participate in decision-making.

8. My patient cannot be delirious because he or she is oriented to time and place

Simple orientation questions can miss subtle signs of delirium. Watch for an inability to function cognitively at the individual’s baseline level. For example, a software engineer who is unable to draw a clock could be delirious.

9. My patient has depression, not delirium, because he or she is not getting out of bed

Delirium can present with changes of mood, energy, and personality that mimic depression. Even severely depressed individuals can function at a basic cognitive level and maintain daytime wakefulness, whereas patients with delirium may not.

10. Delirium cannot be treated

Manage delirium by evaluating and treating underlying medical precipitants such as metabolic derangement, infection, dehydration, hypoxia, pain, or medication effects. Also consider CNS injuries including stroke, head injury, or neoplasm. Research suggests antipsychotic medications at low dosages^6,7 can safely treat delirium. Improving orientation and comfort by reassuring the patient, assessing for anxiety, and reducing excessive noise and stimulation also help.

A consultation-liaison psychiatrist is called in to help manage “schizophrenia” in a middle-aged attorney who is recovering from a complicated cardiac bypass procedure. This patient is not mentally ill, the psychiatrist realizes, but has delirium with rapid-onset neuropsychiatric symptoms noted by fluctuations in arousal and associated changes in sleep, mood, personality, and cognition. This example illustrates 1 of 10 myths about delirium:

1. My patient is paranoid, therefore he or she must be schizophrenic

Patients with delirium may present with perceptual disturbances such as hallucinations, delusions, or paranoia. An otherwise highly functioning individual with symptom onset while in a medical setting likely has delirium, not a chronic mental disorder such as schizophrenia.

2. Delirium is rare

Delirium is found frequently in medically ill populations. In some groups, such as stem-cell transplant patients, rates may approach 50%. Risk factors include medical severity and advanced patient age.¹

3. Delirium is not serious

Delirium is associated with increased morbidity and mortality. It is a marker for “cerebral insufficiency”—reversible impairment in brain function—and requires prompt treatment.^2-4

4. Sleep deprivation causes delirium

Disrupted sleep in hospitalized patients—otherwise known as “ICU psychosis”—is more likely the result of delirium than the cause. Patients’ delirium and sleep both improve when they move from the ICU to a general medical floor, a reflection of their improved medical condition.⁵

5. Delirium goes away rapidly

Delirium usually lasts for days or weeks. Many patients—although superficially improved—still have subtle cognitive deficits and difficulty with daily activities.

6. The patient’s medical problem has been treated, so the delirium should resolve

A patient’s CNS often needs time to recover, and delirium may persist after the underlying medical cause has been treated. Delirium can be caused by factors other than medical illness, such as sedating, analgesic, or antiemetic medications.

7. My delirious patient cannot make medical decisions

Many patients with delirium can make decisions during more lucid periods. As their delirium improves, they should be able to participate in decision-making.

8. My patient cannot be delirious because he or she is oriented to time and place

Simple orientation questions can miss subtle signs of delirium. Watch for an inability to function cognitively at the individual’s baseline level. For example, a software engineer who is unable to draw a clock could be delirious.

9. My patient has depression, not delirium, because he or she is not getting out of bed

Delirium can present with changes of mood, energy, and personality that mimic depression. Even severely depressed individuals can function at a basic cognitive level and maintain daytime wakefulness, whereas patients with delirium may not.

10. Delirium cannot be treated

Manage delirium by evaluating and treating underlying medical precipitants such as metabolic derangement, infection, dehydration, hypoxia, pain, or medication effects. Also consider CNS injuries including stroke, head injury, or neoplasm. Research suggests antipsychotic medications at low dosages^6,7 can safely treat delirium. Improving orientation and comfort by reassuring the patient, assessing for anxiety, and reducing excessive noise and stimulation also help.

Mrs. M, 35, is undergoing breast cancer treatment. She is referred to the consultation-liaison service by an emergency room physician for evaluation of suicidal thoughts.

Mrs. M has been crying for 2 hours. She awoke this morning feeling that she could no longer deal with “the unknown.” She has lost her hair and 30 pounds during chemotherapy and hardly recognized herself in the bathroom mirror. She thought about killing herself until one of her children walked by. After they went to school, she drove to the emergency room.

When you ask if she has had other thoughts of hurting herself, she says, “I would never do anything like that to my family, but the fact that I was thinking about it really scared me.”

Each patient responds uniquely to the emotional trauma of having a chronic or life-threatening medical illness. Coping styles depend on medical, psychological, and social factors as well as the person’s personality and experiences. Reactions range from mature to psychotic.

To help you guide patients such as Mrs. M through difficult medical treatments and decisions, we describe:

• a psychiatric workup to identify maladaptive response to illness
• typical emotional and behavioral responses to chronic illness
• how to provide psychotherapy tailored to the needs of 7 personality styles of medically ill patients.

Psychiatric Workup

Mrs. M is married with 3 sons. She found a lump on her breast 4 months ago but decided to wait “because, I thought, ‘it can’t be anything bad; it will go away.’” When the lump remained 3 months later, she consulted a specialist who diagnosed breast cancer.

Mrs. M underwent a lumpectomy and has been receiving weekly chemotherapy. Besides losing her hair, she says she has no appetite. Looking at food or driving close to the hospital makes her nauseous. She starts vomiting before she arrives for chemotherapy.

Though her family supports and encourages her, she can’t stop thinking about death. She feels isolated, lonely, and cries often. “No one understands what I am going through,” she says. “How can I share these feelings with them?”

Physicians such as the specialist who diagnosed Mrs. M’s cancer often must communicate difficult information. Careful planning when delivering bad news (Box 1)^1,2 can set the stage for a healthier emotional and behavioral response.

Chronic illness causes depression in up to 25% of patients.³ At particular risk of developing depressive symptoms are patients with:

• poor physical condition
• poorly controlled pain
• advanced illness
• history of major depressive disorder
• family history of depression and suicide
• certain cancers, such as of the pancreas, lung, head or neck.⁴

Mechanisms of depression in illness. Depression can be the first symptom of some medical illnesses, such as pancreatic or liver cancer. Diseases that directly affect the brain—such as Parkinson’s disease, multiple sclerosis, and systemic lupus erythematosus—can cause depression. Patients disabled by spinal cord injury, stroke, or cancer also are at risk for depression.

Treatment is the same, whether illness-related chemical changes or the patient’s emotional response to disability is causing the depression. When diagnosing depression in medically ill patients, DSM-IV-TR recommends using criteria for major depression and providing treatment, whatever the cause.

Mrs. M has trouble sharing feelings of hopelessness with her family. Her changes in demeanor and isolation from everyday activities are clues to clinical depression and anxiety.

Depression can be difficult to diagnose when medical illness causes depression-like symptoms.⁵ To make the diagnosis, ask patients with chronic illness about depression’s emotional symptoms (hopelessness, withdrawal from others, sadness, ruminating thoughts, frequent crying spells), rather than its physical symptoms of poor eating, disturbed sleep, or low energy that may stem from the medical illness. Patients might not be as hard on themselves if they feel the medical illness—not poor coping on their part—caused their depression.

Box 1 6 steps for delivering bad medical news

Source: Adapted from references 1, 2Workup. Our workup of Mrs. M includes thyroid function tests, CBC, comprehensive metabolic panel, and brain MRI to rule out metastasis. All are negative. In her history, Mrs. M reports a previous episode of major depression 5 years ago that was successfully treated with sertraline for 1 year.

Consistent with her workup and symptoms, we diagnose major depression without psychosis. Cancer patients who report hopelessness are at increased risk of suicide. Because of her family support and religious beliefs, however, we feel she can safely go home and return for follow-up the next week.

Emotional response to illness

Mrs. M starts weekly outpatient appointments at our clinic. Because sertraline has worked for her in the past, it is our first choice to increase her energy, improve her mood, and decrease her hopelessness. Initial dosage is 25 mg/d for the first 3 days, with an increase to 50 mg/d for 1 month, and 100 mg/d thereafter. She reports no side effects.

In some patients, sertraline can cause adverse gastrointestinal effects such as upset stomach or nausea. Other antidepressants such as mirtazapine could improve patients’ sleep and decrease nausea.

Mrs. M also begins cognitive-behavioral therapy (CBT) to help her deal with negative thoughts, and relaxation training to combat her anxiety before chemotherapy. We recommend a local breast cancer support group, and Mrs. M starts going twice a month. She feels relieved that other patients are experiencing feelings similar to hers.

Medication plus CBT has been shown to be the most effective treatment for patients who meet criteria for depression and anxiety disorders. CBT has been shown to help patients manage physical symptoms and reframe negative thoughts associated with many chronic illnesses, including breast cancer, Parkinson’s disease, epilepsy, rheumatoid arthritis, and multiple sclerosis.^6-10

Core emotions. Medically ill patients experience a range of core emotions, which Lazarus¹¹ identified as anger, anxiety, guilt, fright, shame, sadness, happiness, envy, relief, and hope. Identifying the source of these emotions is important to counseling patients effectively.

For example, a patient experiencing fright might fear death, pain, disability, stigma, disfigurement, or other eventualities. Mrs. M has said she can’t stop thinking about dying. By knowing what the patient fears (Table 1),¹² we can more effectively reassure and offer support, even when little else can be done.

Table 1

Common fears of patients reacting to diagnosis of chronic illness

Defensive behaviors. Patient’s behavioral responses may be adaptive or maladaptive; treatment nonadherence is one maladaptive response (Box 2).^13,14 The patient history can suggest how well a person has adapted to past losses and disappointments. Patients may try to protect themselves against emotional and physical pain with psychotic, immature, neurotic, or mature defense mechanisms.¹⁵

Psychotic defenses are characterized by regression until patients lose touch with reality. Delusions and fantasy isolate them from the harshness of a serious medical condition. Antipsychotic medication and patience are often indicated.¹⁶

Immature defenses—as seen in patients with borderline personality disorder—can irritate and alienate the medical team. Physicians may not understand why their best efforts are thwarted or negated. Well-intentioned, caring doctors often try harder when the verbal attacks begin, but soon even the hardiest can wither under the patient’s criticism and threats.

Box 2

Psychiatrists can counsel the medical team to:

• pull back and focus on setting treatment objectives
• encourage the patient to work as a team member to ensure the best possible care
• communicate with the patient and care team to prevent divisions among the staff.

Neurotic defenses are in play when patients blame themselves and suffer internally. Give them ample opportunities to explore their feelings.

Mature defenses are seen in those who show concern for others, may express humor, and can adaptively plan, thus gaining the respect of others. Spirituality and optimism allow them to feel more at peace and less controlled by the illness.

Support these patients by encouraging their coping skills. For example, if spirituality has helped before, it may again strengthen them and their families.

Improving coping skills. By recognizing which patients are struggling, you can provide support to strengthen their coping abilities. Initially, Mrs. M was using neurotic defense mechanisms and internalizing her emotions. With the help of CBT, she begins to rely on more mature defenses. Her improved coping skills allow her to share her feelings during group therapy and with her family.

Encouraging adaptive behavior

Mrs. M is in remission when chemotherapy ends, but she worries that the cancer will come back. “The fear is still there,” she says. “You can’t be called a survivor for 5 years.”

She continues biweekly psychotherapy for the next year, and sertraline, 100 mg/d. She is doing well and has volunteered to help other newly-diagnosed patients at the cancer center.

Personality styles. Kahana and Bibring¹⁷ described 7 personality types that affect how patients cope with illnesses. Based on our experience, we suggest how to observe these styles, identify the emotional pain behind them, and respond in ways that will help each type of patient (Table 2).¹⁷

These personality types are not necessarily personality disorders; rather, they describe pervasive characteristics of coping styles. Some individuals will not match the descriptions of any of these types, and others may fall into more than one. Mrs. M, for example, shows traits of more than one personality style, including avoidant and mild schizoid features.

We helped her by engaging her in psychiatric treatment, helping her better understand her medical situation, and restoring her sense of control in making medical decisions. We discussed psycho-therapy as a two-way street, outlining her responsibilities to practice new CBT skills to use during treatment and in remission.

Table 2

Recommended treatment approaches for 7 patient personalities

Supportive therapy. Encourage patients to seek support from family and friends.¹⁸ Some benefit from meeting other patients with the same needs, fears, and questions.¹⁹ The Internet is a good resource to find local support groups.

Becoming sick or disabled and having to change one’s lifestyle can damage a person’s self esteem. Encourage patients to help others by volunteering, participating in research, or engaging in other activities that provide hope, gratification, and a sense of service.²⁰

Some patients regain control and battle their fears by becoming experts on their diseases. This approach will not help those who become anxious learning about prognosis and side effects, however, and prefer to have limited information about their illnesses. Your knowledge of a patient’s personality type can help you determine whether added information might alleviate or worsen that patient’s stress.

Personal transformation can occur when patients face mortality. Their perceptions about what is important and how to achieve their goals can change dramatically.

Related resources

• National Cancer Institute. Coping with cancer. www.cancer.gov/cancertopics/coping.
• American Psychiatric Association. Patient education site with links to topics such as coping with AIDS/HIV, postpartum depression, alcohol abuse, mental health of the elderly, and common childhood disorders. www.healthyminds.org.
• Groves M, Muskin P. Psychological responses to illness. In: Bourgeois JA, Hales RE, Shahrokh N (eds). Textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publishing; 2005:68-88.

Drug brand names

• Mirtazapine • Remeron
• Sertraline • Zoloft

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Mrs. M, 35, is undergoing breast cancer treatment. She is referred to the consultation-liaison service by an emergency room physician for evaluation of suicidal thoughts.

Mrs. M has been crying for 2 hours. She awoke this morning feeling that she could no longer deal with “the unknown.” She has lost her hair and 30 pounds during chemotherapy and hardly recognized herself in the bathroom mirror. She thought about killing herself until one of her children walked by. After they went to school, she drove to the emergency room.

When you ask if she has had other thoughts of hurting herself, she says, “I would never do anything like that to my family, but the fact that I was thinking about it really scared me.”

Each patient responds uniquely to the emotional trauma of having a chronic or life-threatening medical illness. Coping styles depend on medical, psychological, and social factors as well as the person’s personality and experiences. Reactions range from mature to psychotic.

To help you guide patients such as Mrs. M through difficult medical treatments and decisions, we describe:

• a psychiatric workup to identify maladaptive response to illness
• typical emotional and behavioral responses to chronic illness
• how to provide psychotherapy tailored to the needs of 7 personality styles of medically ill patients.

Psychiatric Workup

Mrs. M is married with 3 sons. She found a lump on her breast 4 months ago but decided to wait “because, I thought, ‘it can’t be anything bad; it will go away.’” When the lump remained 3 months later, she consulted a specialist who diagnosed breast cancer.

Mrs. M underwent a lumpectomy and has been receiving weekly chemotherapy. Besides losing her hair, she says she has no appetite. Looking at food or driving close to the hospital makes her nauseous. She starts vomiting before she arrives for chemotherapy.

Though her family supports and encourages her, she can’t stop thinking about death. She feels isolated, lonely, and cries often. “No one understands what I am going through,” she says. “How can I share these feelings with them?”

Physicians such as the specialist who diagnosed Mrs. M’s cancer often must communicate difficult information. Careful planning when delivering bad news (Box 1)^1,2 can set the stage for a healthier emotional and behavioral response.

Chronic illness causes depression in up to 25% of patients.³ At particular risk of developing depressive symptoms are patients with:

• poor physical condition
• poorly controlled pain
• advanced illness
• history of major depressive disorder
• family history of depression and suicide
• certain cancers, such as of the pancreas, lung, head or neck.⁴

Mechanisms of depression in illness. Depression can be the first symptom of some medical illnesses, such as pancreatic or liver cancer. Diseases that directly affect the brain—such as Parkinson’s disease, multiple sclerosis, and systemic lupus erythematosus—can cause depression. Patients disabled by spinal cord injury, stroke, or cancer also are at risk for depression.

Treatment is the same, whether illness-related chemical changes or the patient’s emotional response to disability is causing the depression. When diagnosing depression in medically ill patients, DSM-IV-TR recommends using criteria for major depression and providing treatment, whatever the cause.

Mrs. M has trouble sharing feelings of hopelessness with her family. Her changes in demeanor and isolation from everyday activities are clues to clinical depression and anxiety.

Depression can be difficult to diagnose when medical illness causes depression-like symptoms.⁵ To make the diagnosis, ask patients with chronic illness about depression’s emotional symptoms (hopelessness, withdrawal from others, sadness, ruminating thoughts, frequent crying spells), rather than its physical symptoms of poor eating, disturbed sleep, or low energy that may stem from the medical illness. Patients might not be as hard on themselves if they feel the medical illness—not poor coping on their part—caused their depression.

Box 1 6 steps for delivering bad medical news

Source: Adapted from references 1, 2Workup. Our workup of Mrs. M includes thyroid function tests, CBC, comprehensive metabolic panel, and brain MRI to rule out metastasis. All are negative. In her history, Mrs. M reports a previous episode of major depression 5 years ago that was successfully treated with sertraline for 1 year.

Consistent with her workup and symptoms, we diagnose major depression without psychosis. Cancer patients who report hopelessness are at increased risk of suicide. Because of her family support and religious beliefs, however, we feel she can safely go home and return for follow-up the next week.

Emotional response to illness

Mrs. M starts weekly outpatient appointments at our clinic. Because sertraline has worked for her in the past, it is our first choice to increase her energy, improve her mood, and decrease her hopelessness. Initial dosage is 25 mg/d for the first 3 days, with an increase to 50 mg/d for 1 month, and 100 mg/d thereafter. She reports no side effects.

In some patients, sertraline can cause adverse gastrointestinal effects such as upset stomach or nausea. Other antidepressants such as mirtazapine could improve patients’ sleep and decrease nausea.

Mrs. M also begins cognitive-behavioral therapy (CBT) to help her deal with negative thoughts, and relaxation training to combat her anxiety before chemotherapy. We recommend a local breast cancer support group, and Mrs. M starts going twice a month. She feels relieved that other patients are experiencing feelings similar to hers.

Medication plus CBT has been shown to be the most effective treatment for patients who meet criteria for depression and anxiety disorders. CBT has been shown to help patients manage physical symptoms and reframe negative thoughts associated with many chronic illnesses, including breast cancer, Parkinson’s disease, epilepsy, rheumatoid arthritis, and multiple sclerosis.^6-10

Core emotions. Medically ill patients experience a range of core emotions, which Lazarus¹¹ identified as anger, anxiety, guilt, fright, shame, sadness, happiness, envy, relief, and hope. Identifying the source of these emotions is important to counseling patients effectively.

For example, a patient experiencing fright might fear death, pain, disability, stigma, disfigurement, or other eventualities. Mrs. M has said she can’t stop thinking about dying. By knowing what the patient fears (Table 1),¹² we can more effectively reassure and offer support, even when little else can be done.

Table 1

Common fears of patients reacting to diagnosis of chronic illness

Defensive behaviors. Patient’s behavioral responses may be adaptive or maladaptive; treatment nonadherence is one maladaptive response (Box 2).^13,14 The patient history can suggest how well a person has adapted to past losses and disappointments. Patients may try to protect themselves against emotional and physical pain with psychotic, immature, neurotic, or mature defense mechanisms.¹⁵

Psychotic defenses are characterized by regression until patients lose touch with reality. Delusions and fantasy isolate them from the harshness of a serious medical condition. Antipsychotic medication and patience are often indicated.¹⁶

Immature defenses—as seen in patients with borderline personality disorder—can irritate and alienate the medical team. Physicians may not understand why their best efforts are thwarted or negated. Well-intentioned, caring doctors often try harder when the verbal attacks begin, but soon even the hardiest can wither under the patient’s criticism and threats.

Box 2

Psychiatrists can counsel the medical team to:

• pull back and focus on setting treatment objectives
• encourage the patient to work as a team member to ensure the best possible care
• communicate with the patient and care team to prevent divisions among the staff.

Neurotic defenses are in play when patients blame themselves and suffer internally. Give them ample opportunities to explore their feelings.

Mature defenses are seen in those who show concern for others, may express humor, and can adaptively plan, thus gaining the respect of others. Spirituality and optimism allow them to feel more at peace and less controlled by the illness.

Support these patients by encouraging their coping skills. For example, if spirituality has helped before, it may again strengthen them and their families.

Improving coping skills. By recognizing which patients are struggling, you can provide support to strengthen their coping abilities. Initially, Mrs. M was using neurotic defense mechanisms and internalizing her emotions. With the help of CBT, she begins to rely on more mature defenses. Her improved coping skills allow her to share her feelings during group therapy and with her family.

Encouraging adaptive behavior

Mrs. M is in remission when chemotherapy ends, but she worries that the cancer will come back. “The fear is still there,” she says. “You can’t be called a survivor for 5 years.”

She continues biweekly psychotherapy for the next year, and sertraline, 100 mg/d. She is doing well and has volunteered to help other newly-diagnosed patients at the cancer center.

Personality styles. Kahana and Bibring¹⁷ described 7 personality types that affect how patients cope with illnesses. Based on our experience, we suggest how to observe these styles, identify the emotional pain behind them, and respond in ways that will help each type of patient (Table 2).¹⁷

These personality types are not necessarily personality disorders; rather, they describe pervasive characteristics of coping styles. Some individuals will not match the descriptions of any of these types, and others may fall into more than one. Mrs. M, for example, shows traits of more than one personality style, including avoidant and mild schizoid features.

We helped her by engaging her in psychiatric treatment, helping her better understand her medical situation, and restoring her sense of control in making medical decisions. We discussed psycho-therapy as a two-way street, outlining her responsibilities to practice new CBT skills to use during treatment and in remission.

Table 2

Recommended treatment approaches for 7 patient personalities

Supportive therapy. Encourage patients to seek support from family and friends.¹⁸ Some benefit from meeting other patients with the same needs, fears, and questions.¹⁹ The Internet is a good resource to find local support groups.

Becoming sick or disabled and having to change one’s lifestyle can damage a person’s self esteem. Encourage patients to help others by volunteering, participating in research, or engaging in other activities that provide hope, gratification, and a sense of service.²⁰

Some patients regain control and battle their fears by becoming experts on their diseases. This approach will not help those who become anxious learning about prognosis and side effects, however, and prefer to have limited information about their illnesses. Your knowledge of a patient’s personality type can help you determine whether added information might alleviate or worsen that patient’s stress.

Personal transformation can occur when patients face mortality. Their perceptions about what is important and how to achieve their goals can change dramatically.

Related resources

• National Cancer Institute. Coping with cancer. www.cancer.gov/cancertopics/coping.
• American Psychiatric Association. Patient education site with links to topics such as coping with AIDS/HIV, postpartum depression, alcohol abuse, mental health of the elderly, and common childhood disorders. www.healthyminds.org.
• Groves M, Muskin P. Psychological responses to illness. In: Bourgeois JA, Hales RE, Shahrokh N (eds). Textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publishing; 2005:68-88.

Drug brand names

• Mirtazapine • Remeron
• Sertraline • Zoloft

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Mrs. M, 35, is undergoing breast cancer treatment. She is referred to the consultation-liaison service by an emergency room physician for evaluation of suicidal thoughts.

Mrs. M has been crying for 2 hours. She awoke this morning feeling that she could no longer deal with “the unknown.” She has lost her hair and 30 pounds during chemotherapy and hardly recognized herself in the bathroom mirror. She thought about killing herself until one of her children walked by. After they went to school, she drove to the emergency room.

When you ask if she has had other thoughts of hurting herself, she says, “I would never do anything like that to my family, but the fact that I was thinking about it really scared me.”

Each patient responds uniquely to the emotional trauma of having a chronic or life-threatening medical illness. Coping styles depend on medical, psychological, and social factors as well as the person’s personality and experiences. Reactions range from mature to psychotic.

To help you guide patients such as Mrs. M through difficult medical treatments and decisions, we describe:

• a psychiatric workup to identify maladaptive response to illness
• typical emotional and behavioral responses to chronic illness
• how to provide psychotherapy tailored to the needs of 7 personality styles of medically ill patients.

Psychiatric Workup

Mrs. M is married with 3 sons. She found a lump on her breast 4 months ago but decided to wait “because, I thought, ‘it can’t be anything bad; it will go away.’” When the lump remained 3 months later, she consulted a specialist who diagnosed breast cancer.

Mrs. M underwent a lumpectomy and has been receiving weekly chemotherapy. Besides losing her hair, she says she has no appetite. Looking at food or driving close to the hospital makes her nauseous. She starts vomiting before she arrives for chemotherapy.

Though her family supports and encourages her, she can’t stop thinking about death. She feels isolated, lonely, and cries often. “No one understands what I am going through,” she says. “How can I share these feelings with them?”

Physicians such as the specialist who diagnosed Mrs. M’s cancer often must communicate difficult information. Careful planning when delivering bad news (Box 1)^1,2 can set the stage for a healthier emotional and behavioral response.

Chronic illness causes depression in up to 25% of patients.³ At particular risk of developing depressive symptoms are patients with:

• poor physical condition
• poorly controlled pain
• advanced illness
• history of major depressive disorder
• family history of depression and suicide
• certain cancers, such as of the pancreas, lung, head or neck.⁴

Mechanisms of depression in illness. Depression can be the first symptom of some medical illnesses, such as pancreatic or liver cancer. Diseases that directly affect the brain—such as Parkinson’s disease, multiple sclerosis, and systemic lupus erythematosus—can cause depression. Patients disabled by spinal cord injury, stroke, or cancer also are at risk for depression.

Treatment is the same, whether illness-related chemical changes or the patient’s emotional response to disability is causing the depression. When diagnosing depression in medically ill patients, DSM-IV-TR recommends using criteria for major depression and providing treatment, whatever the cause.

Mrs. M has trouble sharing feelings of hopelessness with her family. Her changes in demeanor and isolation from everyday activities are clues to clinical depression and anxiety.

Depression can be difficult to diagnose when medical illness causes depression-like symptoms.⁵ To make the diagnosis, ask patients with chronic illness about depression’s emotional symptoms (hopelessness, withdrawal from others, sadness, ruminating thoughts, frequent crying spells), rather than its physical symptoms of poor eating, disturbed sleep, or low energy that may stem from the medical illness. Patients might not be as hard on themselves if they feel the medical illness—not poor coping on their part—caused their depression.

Box 1 6 steps for delivering bad medical news

Source: Adapted from references 1, 2Workup. Our workup of Mrs. M includes thyroid function tests, CBC, comprehensive metabolic panel, and brain MRI to rule out metastasis. All are negative. In her history, Mrs. M reports a previous episode of major depression 5 years ago that was successfully treated with sertraline for 1 year.

Consistent with her workup and symptoms, we diagnose major depression without psychosis. Cancer patients who report hopelessness are at increased risk of suicide. Because of her family support and religious beliefs, however, we feel she can safely go home and return for follow-up the next week.

Emotional response to illness

Mrs. M starts weekly outpatient appointments at our clinic. Because sertraline has worked for her in the past, it is our first choice to increase her energy, improve her mood, and decrease her hopelessness. Initial dosage is 25 mg/d for the first 3 days, with an increase to 50 mg/d for 1 month, and 100 mg/d thereafter. She reports no side effects.

In some patients, sertraline can cause adverse gastrointestinal effects such as upset stomach or nausea. Other antidepressants such as mirtazapine could improve patients’ sleep and decrease nausea.

Mrs. M also begins cognitive-behavioral therapy (CBT) to help her deal with negative thoughts, and relaxation training to combat her anxiety before chemotherapy. We recommend a local breast cancer support group, and Mrs. M starts going twice a month. She feels relieved that other patients are experiencing feelings similar to hers.

Medication plus CBT has been shown to be the most effective treatment for patients who meet criteria for depression and anxiety disorders. CBT has been shown to help patients manage physical symptoms and reframe negative thoughts associated with many chronic illnesses, including breast cancer, Parkinson’s disease, epilepsy, rheumatoid arthritis, and multiple sclerosis.^6-10

Core emotions. Medically ill patients experience a range of core emotions, which Lazarus¹¹ identified as anger, anxiety, guilt, fright, shame, sadness, happiness, envy, relief, and hope. Identifying the source of these emotions is important to counseling patients effectively.

For example, a patient experiencing fright might fear death, pain, disability, stigma, disfigurement, or other eventualities. Mrs. M has said she can’t stop thinking about dying. By knowing what the patient fears (Table 1),¹² we can more effectively reassure and offer support, even when little else can be done.

Table 1

Common fears of patients reacting to diagnosis of chronic illness

Defensive behaviors. Patient’s behavioral responses may be adaptive or maladaptive; treatment nonadherence is one maladaptive response (Box 2).^13,14 The patient history can suggest how well a person has adapted to past losses and disappointments. Patients may try to protect themselves against emotional and physical pain with psychotic, immature, neurotic, or mature defense mechanisms.¹⁵

Psychotic defenses are characterized by regression until patients lose touch with reality. Delusions and fantasy isolate them from the harshness of a serious medical condition. Antipsychotic medication and patience are often indicated.¹⁶

Immature defenses—as seen in patients with borderline personality disorder—can irritate and alienate the medical team. Physicians may not understand why their best efforts are thwarted or negated. Well-intentioned, caring doctors often try harder when the verbal attacks begin, but soon even the hardiest can wither under the patient’s criticism and threats.

Box 2

Psychiatrists can counsel the medical team to:

• pull back and focus on setting treatment objectives
• encourage the patient to work as a team member to ensure the best possible care
• communicate with the patient and care team to prevent divisions among the staff.

Neurotic defenses are in play when patients blame themselves and suffer internally. Give them ample opportunities to explore their feelings.

Mature defenses are seen in those who show concern for others, may express humor, and can adaptively plan, thus gaining the respect of others. Spirituality and optimism allow them to feel more at peace and less controlled by the illness.

Support these patients by encouraging their coping skills. For example, if spirituality has helped before, it may again strengthen them and their families.

Improving coping skills. By recognizing which patients are struggling, you can provide support to strengthen their coping abilities. Initially, Mrs. M was using neurotic defense mechanisms and internalizing her emotions. With the help of CBT, she begins to rely on more mature defenses. Her improved coping skills allow her to share her feelings during group therapy and with her family.

Encouraging adaptive behavior

Mrs. M is in remission when chemotherapy ends, but she worries that the cancer will come back. “The fear is still there,” she says. “You can’t be called a survivor for 5 years.”

She continues biweekly psychotherapy for the next year, and sertraline, 100 mg/d. She is doing well and has volunteered to help other newly-diagnosed patients at the cancer center.

Personality styles. Kahana and Bibring¹⁷ described 7 personality types that affect how patients cope with illnesses. Based on our experience, we suggest how to observe these styles, identify the emotional pain behind them, and respond in ways that will help each type of patient (Table 2).¹⁷

These personality types are not necessarily personality disorders; rather, they describe pervasive characteristics of coping styles. Some individuals will not match the descriptions of any of these types, and others may fall into more than one. Mrs. M, for example, shows traits of more than one personality style, including avoidant and mild schizoid features.

We helped her by engaging her in psychiatric treatment, helping her better understand her medical situation, and restoring her sense of control in making medical decisions. We discussed psycho-therapy as a two-way street, outlining her responsibilities to practice new CBT skills to use during treatment and in remission.

Table 2

Recommended treatment approaches for 7 patient personalities

Supportive therapy. Encourage patients to seek support from family and friends.¹⁸ Some benefit from meeting other patients with the same needs, fears, and questions.¹⁹ The Internet is a good resource to find local support groups.

Becoming sick or disabled and having to change one’s lifestyle can damage a person’s self esteem. Encourage patients to help others by volunteering, participating in research, or engaging in other activities that provide hope, gratification, and a sense of service.²⁰

Some patients regain control and battle their fears by becoming experts on their diseases. This approach will not help those who become anxious learning about prognosis and side effects, however, and prefer to have limited information about their illnesses. Your knowledge of a patient’s personality type can help you determine whether added information might alleviate or worsen that patient’s stress.

Personal transformation can occur when patients face mortality. Their perceptions about what is important and how to achieve their goals can change dramatically.

Related resources

• National Cancer Institute. Coping with cancer. www.cancer.gov/cancertopics/coping.
• American Psychiatric Association. Patient education site with links to topics such as coping with AIDS/HIV, postpartum depression, alcohol abuse, mental health of the elderly, and common childhood disorders. www.healthyminds.org.
• Groves M, Muskin P. Psychological responses to illness. In: Bourgeois JA, Hales RE, Shahrokh N (eds). Textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publishing; 2005:68-88.

Drug brand names

• Mirtazapine • Remeron
• Sertraline • Zoloft

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

The headline “ECT wipes out 30 years of memories” (Current Psychiatry, August 2006) is unsupported by data presented in the article. I assume the decision to sensationalize the subject was an editorial one, as Dr. Jon Grant’s comments otherwise are suitably cautious, measured, and correct.

The case presented did not state whether unilateral or bilateral electrode placement was used to administer daily electroconvulsive therapy (ECT) for 10 days, but daily bilateral placement is not recommended by any authority or textbook and is not considered standard. My research has shown that daily unilateral ECT administered 5 days per week for a total of 20 treatments does not affect memory adversely.¹

The claim that “the patient suffered severe brain damage and lost all her memories for the past 30 years” also is unsupported. In fact, there is no published evidence that any form of ECT can cause brain damage or permanent memory loss, a subject I have reviewed in considerable detail.²

Richard Abrams, MD
Professor of psychiatry (retired)
Rosalind Franklin University of Medicine and Science
Director of Somatics LLC, manufacturer of ECT equipment
Chicago, IL

References

1. Abrams R. Daily administration of unilateral ECT. Amer J Psychiat 1967;124(3):384-6.

2. Abrams R. Electroconvulsive therapy. 4th ed. New York, NY: Oxford University Press; 2002.

Dr. Grant responds

Dr. Abrams’ letter reflects the ongoing controversy regarding ECT-associated memory loss.

Although Dr. Abrams states that there is no evidence of permanent memory loss associated with ECT, rare cases such as the one presented in the article—where a patient reports losing memories dating back 30 years—call into question ECT’s potential cognitive side effects. Sackeim points to evidence of severe, persistent retrograde amnesia in some ECT cases, which may extend several years prior to treatment.¹

In a published, first-person account, an ECT patient describes memory loss of major life events dating back 8 to 9 years.² Although the memory loss caused significant impairment, the author says she would undergo ECT again.

Further research ultimately may clarify this ongoing controversy. In fact, the first large prospective study of ECT’s cognitive effects has been published recently.³ In a study of 347 patients in 7 facilities, the researchers found that sine wave stimulation resulted in pronounced reaction time slowing, both immediately and 6 months following ECT. Bilateral ECT resulted in more-severe, persistent retrograde amnesia than did right unilateral ECT. Advanced age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits.

Given the ongoing controversy about ECT’s cognitive side effects, clinicians should make patients aware of this ongoing discussion and the evidence on both sides of the debate.

Jon E. Grant, JD, MD, MPH
Associate professor of psychiatry
University of Minnesota Medical Center, Minneapolis

The headline “ECT wipes out 30 years of memories” (Current Psychiatry, August 2006) is unsupported by data presented in the article. I assume the decision to sensationalize the subject was an editorial one, as Dr. Jon Grant’s comments otherwise are suitably cautious, measured, and correct.

The case presented did not state whether unilateral or bilateral electrode placement was used to administer daily electroconvulsive therapy (ECT) for 10 days, but daily bilateral placement is not recommended by any authority or textbook and is not considered standard. My research has shown that daily unilateral ECT administered 5 days per week for a total of 20 treatments does not affect memory adversely.¹

The claim that “the patient suffered severe brain damage and lost all her memories for the past 30 years” also is unsupported. In fact, there is no published evidence that any form of ECT can cause brain damage or permanent memory loss, a subject I have reviewed in considerable detail.²

Richard Abrams, MD
Professor of psychiatry (retired)
Rosalind Franklin University of Medicine and Science
Director of Somatics LLC, manufacturer of ECT equipment
Chicago, IL

References

1. Abrams R. Daily administration of unilateral ECT. Amer J Psychiat 1967;124(3):384-6.

2. Abrams R. Electroconvulsive therapy. 4th ed. New York, NY: Oxford University Press; 2002.

Dr. Grant responds

Dr. Abrams’ letter reflects the ongoing controversy regarding ECT-associated memory loss.

Although Dr. Abrams states that there is no evidence of permanent memory loss associated with ECT, rare cases such as the one presented in the article—where a patient reports losing memories dating back 30 years—call into question ECT’s potential cognitive side effects. Sackeim points to evidence of severe, persistent retrograde amnesia in some ECT cases, which may extend several years prior to treatment.¹

In a published, first-person account, an ECT patient describes memory loss of major life events dating back 8 to 9 years.² Although the memory loss caused significant impairment, the author says she would undergo ECT again.

Further research ultimately may clarify this ongoing controversy. In fact, the first large prospective study of ECT’s cognitive effects has been published recently.³ In a study of 347 patients in 7 facilities, the researchers found that sine wave stimulation resulted in pronounced reaction time slowing, both immediately and 6 months following ECT. Bilateral ECT resulted in more-severe, persistent retrograde amnesia than did right unilateral ECT. Advanced age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits.

Given the ongoing controversy about ECT’s cognitive side effects, clinicians should make patients aware of this ongoing discussion and the evidence on both sides of the debate.

Jon E. Grant, JD, MD, MPH
Associate professor of psychiatry
University of Minnesota Medical Center, Minneapolis

The headline “ECT wipes out 30 years of memories” (Current Psychiatry, August 2006) is unsupported by data presented in the article. I assume the decision to sensationalize the subject was an editorial one, as Dr. Jon Grant’s comments otherwise are suitably cautious, measured, and correct.

The case presented did not state whether unilateral or bilateral electrode placement was used to administer daily electroconvulsive therapy (ECT) for 10 days, but daily bilateral placement is not recommended by any authority or textbook and is not considered standard. My research has shown that daily unilateral ECT administered 5 days per week for a total of 20 treatments does not affect memory adversely.¹

The claim that “the patient suffered severe brain damage and lost all her memories for the past 30 years” also is unsupported. In fact, there is no published evidence that any form of ECT can cause brain damage or permanent memory loss, a subject I have reviewed in considerable detail.²

Richard Abrams, MD
Professor of psychiatry (retired)
Rosalind Franklin University of Medicine and Science
Director of Somatics LLC, manufacturer of ECT equipment
Chicago, IL

References

1. Abrams R. Daily administration of unilateral ECT. Amer J Psychiat 1967;124(3):384-6.

2. Abrams R. Electroconvulsive therapy. 4th ed. New York, NY: Oxford University Press; 2002.

Dr. Grant responds

Dr. Abrams’ letter reflects the ongoing controversy regarding ECT-associated memory loss.

Although Dr. Abrams states that there is no evidence of permanent memory loss associated with ECT, rare cases such as the one presented in the article—where a patient reports losing memories dating back 30 years—call into question ECT’s potential cognitive side effects. Sackeim points to evidence of severe, persistent retrograde amnesia in some ECT cases, which may extend several years prior to treatment.¹

In a published, first-person account, an ECT patient describes memory loss of major life events dating back 8 to 9 years.² Although the memory loss caused significant impairment, the author says she would undergo ECT again.

Further research ultimately may clarify this ongoing controversy. In fact, the first large prospective study of ECT’s cognitive effects has been published recently.³ In a study of 347 patients in 7 facilities, the researchers found that sine wave stimulation resulted in pronounced reaction time slowing, both immediately and 6 months following ECT. Bilateral ECT resulted in more-severe, persistent retrograde amnesia than did right unilateral ECT. Advanced age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits.

Given the ongoing controversy about ECT’s cognitive side effects, clinicians should make patients aware of this ongoing discussion and the evidence on both sides of the debate.

Jon E. Grant, JD, MD, MPH
Associate professor of psychiatry
University of Minnesota Medical Center, Minneapolis

Reference 20 in “Making an IMPACT on late-life depression” (September 2006) should have been Unützer J, Tang L, Oishi S, et al. Reducing suicidal ideation in depressed older primary care patients. J Am Geriatr Soc [serial online]. Sept. 8, 2006. Available at: www.blackwellsynergy.com/toc/jgs/0/0. The article “ECT wipes out 30 years of memories” (Malpractice Verdicts, August 2006) misstated that the case was settled for $18,000. The jury awarded $625,200 to the patient and found the referring psychiatrist solely liable.

Reference 20 in “Making an IMPACT on late-life depression” (September 2006) should have been Unützer J, Tang L, Oishi S, et al. Reducing suicidal ideation in depressed older primary care patients. J Am Geriatr Soc [serial online]. Sept. 8, 2006. Available at: www.blackwellsynergy.com/toc/jgs/0/0. The article “ECT wipes out 30 years of memories” (Malpractice Verdicts, August 2006) misstated that the case was settled for $18,000. The jury awarded $625,200 to the patient and found the referring psychiatrist solely liable.

Reference 20 in “Making an IMPACT on late-life depression” (September 2006) should have been Unützer J, Tang L, Oishi S, et al. Reducing suicidal ideation in depressed older primary care patients. J Am Geriatr Soc [serial online]. Sept. 8, 2006. Available at: www.blackwellsynergy.com/toc/jgs/0/0. The article “ECT wipes out 30 years of memories” (Malpractice Verdicts, August 2006) misstated that the case was settled for $18,000. The jury awarded $625,200 to the patient and found the referring psychiatrist solely liable.

Pharmacotherapy works for psychiatric disorders, and so does psychotherapy. That’s why I provide both to each of my patients and why Current Psychiatry articles address combination therapy (for example, see “Treating psychiatric reactions to medical illness,”). Many studies have concluded that combining pharmacotherapy and psychotherapy produces better outcomes than either treatment alone.

The apparent synergy between verbal therapy and medications is often observed but rarely investigated. Does it occur because two different mechanisms of action work better than one, such as when we combine a dopamine blocker (antipsychotic) with a GABA agonist (mood stabilizer) in a patient with bipolar mania? Or do drug therapy and psychotherapy share a common pathway that is enhanced when they are administered together, such as when we combine two antidepressants to manage a patient with treatment-resistant depression?

What is psychotherapy’s mechanism of action anyway, and do various modalities—cognitive-behavioral, interpersonal, or supportive—have the same psychobiological mechanism of action?

Psychotherapy’s mechanism

Given the limited evidence and lack of clear answers in this area, it is reasonable to use recent advances in neuroscience to speculate on how two ostensibly different treatment modalities improve clinical manifestations—the mood, thought, and behavior alterations—of psychiatric brain disorders.

Emerging discoveries over the past few years suggest the common pathway of psychotherapy and pharmacotherapy may be neuroplasticity—synaptogenesis, dendritic spines, and neurogenesis. In other words, talking to a person or giving that person a psychotropic are both likely to modify that person’s brain structure.

Unlike any other organ, the brain changes continuously in response to external and internal stimuli, such as verbal, visual, tactile, and olfactory perceptions as well as chemical stimuli. Neural tissue also changes in response to experiences—stressful or pleasurable, real or imagined, emotional or cognitive. Psychotherapy represents a targeted, strategic, and tactical approach to stimulate specific feelings, recollections, and insights. These are encoded into the recipient’s neurobiological pathways and ultimately translate into a change in behavior or symptoms.

Every therapeutic encounter produces neuroplasticity, and—as with drug therapy—the cumulative effect of repeated doses of psychotherapy consolidates the improvement. One way to conceptualize this mechanism is that psychotherapy refurbishes the patient’s brain structure at the molecular level, restoring resilience to a brain/mind system that was compromised by genetic factors or environmental stress.

‘Re-Wiring’ the brain

Where does pharmacotherapy fit into this model? Here, too, evidence is emerging that psychotropics may exert their therapeutic effect not only through neurochemical pathways but also by stimulating neurotropic factors and inducing beneficial neuroplastic changes.

Antidepressants, mood stabilizers, and atypical antipsychotics (but not conventional neuroleptics) have been shown to induce synaptogenesis, neurite extension, and neurogenesis. These actions result in “re-wiring” and “re-sculpting” brain regions such as the hippocampus and subventricular zone.

Psychotropics are known to trigger gene expression within hours for some genes and after days or weeks for others (which may explain short-term alleviation of some symptoms but delayed response of others). Psychotropics’ neuroprotective and neuroplastic effects also appear to help “replenish” brain tissue destroyed by the neurotoxic effects of repetitive psychotic, manic, or depressive relapses. Increases in nerve growth factor, brain-derived neurotropic factor, and fibroblast growth factor have been implicated in brain tissue regeneration in serious psychiatric disorders. Animal and human studies support this model, but more research is needed.

Accelerating Neuroplasticity

Using this neuroplasticity model, we can reasonably postulate that the convergence of psychotherapy with pharmacotherapy may accelerate and expedite the clinical improvement that hinges on “therapeutic restructuring” of certain neural pathways. I find it intriguing to think that by repairing brain tissue with two different stimuli—talking and medicating—we can mend the fractured mind of an ailing brain.

As neuroscientists explore more deeply this area of research, we clinicians will continue to use concomitant pharmacotherapy and psychotherapy to help our patients navigate the road to recovery.

Pharmacotherapy works for psychiatric disorders, and so does psychotherapy. That’s why I provide both to each of my patients and why Current Psychiatry articles address combination therapy (for example, see “Treating psychiatric reactions to medical illness,”). Many studies have concluded that combining pharmacotherapy and psychotherapy produces better outcomes than either treatment alone.

The apparent synergy between verbal therapy and medications is often observed but rarely investigated. Does it occur because two different mechanisms of action work better than one, such as when we combine a dopamine blocker (antipsychotic) with a GABA agonist (mood stabilizer) in a patient with bipolar mania? Or do drug therapy and psychotherapy share a common pathway that is enhanced when they are administered together, such as when we combine two antidepressants to manage a patient with treatment-resistant depression?

What is psychotherapy’s mechanism of action anyway, and do various modalities—cognitive-behavioral, interpersonal, or supportive—have the same psychobiological mechanism of action?

Psychotherapy’s mechanism

Given the limited evidence and lack of clear answers in this area, it is reasonable to use recent advances in neuroscience to speculate on how two ostensibly different treatment modalities improve clinical manifestations—the mood, thought, and behavior alterations—of psychiatric brain disorders.

Emerging discoveries over the past few years suggest the common pathway of psychotherapy and pharmacotherapy may be neuroplasticity—synaptogenesis, dendritic spines, and neurogenesis. In other words, talking to a person or giving that person a psychotropic are both likely to modify that person’s brain structure.

Unlike any other organ, the brain changes continuously in response to external and internal stimuli, such as verbal, visual, tactile, and olfactory perceptions as well as chemical stimuli. Neural tissue also changes in response to experiences—stressful or pleasurable, real or imagined, emotional or cognitive. Psychotherapy represents a targeted, strategic, and tactical approach to stimulate specific feelings, recollections, and insights. These are encoded into the recipient’s neurobiological pathways and ultimately translate into a change in behavior or symptoms.

Every therapeutic encounter produces neuroplasticity, and—as with drug therapy—the cumulative effect of repeated doses of psychotherapy consolidates the improvement. One way to conceptualize this mechanism is that psychotherapy refurbishes the patient’s brain structure at the molecular level, restoring resilience to a brain/mind system that was compromised by genetic factors or environmental stress.

‘Re-Wiring’ the brain

Where does pharmacotherapy fit into this model? Here, too, evidence is emerging that psychotropics may exert their therapeutic effect not only through neurochemical pathways but also by stimulating neurotropic factors and inducing beneficial neuroplastic changes.

Antidepressants, mood stabilizers, and atypical antipsychotics (but not conventional neuroleptics) have been shown to induce synaptogenesis, neurite extension, and neurogenesis. These actions result in “re-wiring” and “re-sculpting” brain regions such as the hippocampus and subventricular zone.

Psychotropics are known to trigger gene expression within hours for some genes and after days or weeks for others (which may explain short-term alleviation of some symptoms but delayed response of others). Psychotropics’ neuroprotective and neuroplastic effects also appear to help “replenish” brain tissue destroyed by the neurotoxic effects of repetitive psychotic, manic, or depressive relapses. Increases in nerve growth factor, brain-derived neurotropic factor, and fibroblast growth factor have been implicated in brain tissue regeneration in serious psychiatric disorders. Animal and human studies support this model, but more research is needed.

Accelerating Neuroplasticity

Using this neuroplasticity model, we can reasonably postulate that the convergence of psychotherapy with pharmacotherapy may accelerate and expedite the clinical improvement that hinges on “therapeutic restructuring” of certain neural pathways. I find it intriguing to think that by repairing brain tissue with two different stimuli—talking and medicating—we can mend the fractured mind of an ailing brain.

As neuroscientists explore more deeply this area of research, we clinicians will continue to use concomitant pharmacotherapy and psychotherapy to help our patients navigate the road to recovery.

Pharmacotherapy works for psychiatric disorders, and so does psychotherapy. That’s why I provide both to each of my patients and why Current Psychiatry articles address combination therapy (for example, see “Treating psychiatric reactions to medical illness,”). Many studies have concluded that combining pharmacotherapy and psychotherapy produces better outcomes than either treatment alone.

The apparent synergy between verbal therapy and medications is often observed but rarely investigated. Does it occur because two different mechanisms of action work better than one, such as when we combine a dopamine blocker (antipsychotic) with a GABA agonist (mood stabilizer) in a patient with bipolar mania? Or do drug therapy and psychotherapy share a common pathway that is enhanced when they are administered together, such as when we combine two antidepressants to manage a patient with treatment-resistant depression?

What is psychotherapy’s mechanism of action anyway, and do various modalities—cognitive-behavioral, interpersonal, or supportive—have the same psychobiological mechanism of action?

Psychotherapy’s mechanism

Given the limited evidence and lack of clear answers in this area, it is reasonable to use recent advances in neuroscience to speculate on how two ostensibly different treatment modalities improve clinical manifestations—the mood, thought, and behavior alterations—of psychiatric brain disorders.

Emerging discoveries over the past few years suggest the common pathway of psychotherapy and pharmacotherapy may be neuroplasticity—synaptogenesis, dendritic spines, and neurogenesis. In other words, talking to a person or giving that person a psychotropic are both likely to modify that person’s brain structure.

Unlike any other organ, the brain changes continuously in response to external and internal stimuli, such as verbal, visual, tactile, and olfactory perceptions as well as chemical stimuli. Neural tissue also changes in response to experiences—stressful or pleasurable, real or imagined, emotional or cognitive. Psychotherapy represents a targeted, strategic, and tactical approach to stimulate specific feelings, recollections, and insights. These are encoded into the recipient’s neurobiological pathways and ultimately translate into a change in behavior or symptoms.

Every therapeutic encounter produces neuroplasticity, and—as with drug therapy—the cumulative effect of repeated doses of psychotherapy consolidates the improvement. One way to conceptualize this mechanism is that psychotherapy refurbishes the patient’s brain structure at the molecular level, restoring resilience to a brain/mind system that was compromised by genetic factors or environmental stress.

‘Re-Wiring’ the brain

Where does pharmacotherapy fit into this model? Here, too, evidence is emerging that psychotropics may exert their therapeutic effect not only through neurochemical pathways but also by stimulating neurotropic factors and inducing beneficial neuroplastic changes.

Antidepressants, mood stabilizers, and atypical antipsychotics (but not conventional neuroleptics) have been shown to induce synaptogenesis, neurite extension, and neurogenesis. These actions result in “re-wiring” and “re-sculpting” brain regions such as the hippocampus and subventricular zone.

Psychotropics are known to trigger gene expression within hours for some genes and after days or weeks for others (which may explain short-term alleviation of some symptoms but delayed response of others). Psychotropics’ neuroprotective and neuroplastic effects also appear to help “replenish” brain tissue destroyed by the neurotoxic effects of repetitive psychotic, manic, or depressive relapses. Increases in nerve growth factor, brain-derived neurotropic factor, and fibroblast growth factor have been implicated in brain tissue regeneration in serious psychiatric disorders. Animal and human studies support this model, but more research is needed.

Accelerating Neuroplasticity

Using this neuroplasticity model, we can reasonably postulate that the convergence of psychotherapy with pharmacotherapy may accelerate and expedite the clinical improvement that hinges on “therapeutic restructuring” of certain neural pathways. I find it intriguing to think that by repairing brain tissue with two different stimuli—talking and medicating—we can mend the fractured mind of an ailing brain.

As neuroscientists explore more deeply this area of research, we clinicians will continue to use concomitant pharmacotherapy and psychotherapy to help our patients navigate the road to recovery.

History: a lovelorn life

Ms. F, age 33, presents with one complaint: “I want to know how to maintain a relationship.” Problem is, social situations have made her feel anxious since childhood. She has trouble keeping a boyfriend; she left two intimate, extended relationships at different times.

She says she is too ashamed to invite people over because she cannot keep her apartment neat. She is also sick of her job as a filing clerk and wants a new career.

Ms. F reports no other anxiety symptoms or mood changes but often cannot concentrate. She denies impulsivity or poor judgment but admits that she makes decisions without getting important facts. For example, she enrolled at a community college without knowing what skills her new career would require. About 6 months ago, she left her boyfriend after realizing—18 months into the relationship—that he does not share her interests.

poll here

The authors’ observations

Information on all the above factors is crucial to diagnosing a socialization problem. Outline your differential diagnosis as the interview progresses.

Ask the patient:

How did you fare in school? A childhood history of pervasive inattention or impulsivity in at least two settings (at home and in school, for example) can signal attention-deficit/hyperactivity disorder (ADHD).^{fragile X syndrome). Boys with the fragile X premutation have a higher rate of ADHD symptoms and autism spectrum disorders than do boys without this premutation.3 Ms. F’s test showed two normal alleles, thus ruling out fragile X premutation.}

Table 1

Mental status examination signs that suggest a PDD

Treatment: medication and exploration

Ms. F agrees to an ADOS test. Her total score of 9 (7 in social, 2 in communication, and 0 in stereotyped/repetitive behavior) suggest a moderate PDD. We rule out autism based on the test score and Asperger’s syndrome because of her early language development delays (Table 2).

We start escitalopram, 10 mg/d, to address Ms. F’s anxiety. We see her weekly for medication management and start weekly psychotherapy to explore her two previous relationships and her desire to find a partner.

Ms. F, however, reacts anxiously to the therapist’s exploratory techniques. She has difficulty taking the lead and becomes extremely uncomfortable with silences in the conversation. The therapist tries cognitive-behavioral tactics to engage her, but Ms. F does not respond.

The therapist then conceptualizes her role as “coach” and tries a more-direct, problem-solving approach. She addresses specific challenges, such as an overwhelming class assignment, but Ms. F does not discuss or follow through on the problem.

After 6 months, Ms. F asks to stop psychotherapy because she has made little progress. She also asks to reduce medication checks to monthly, saying that weekly sessions interfere with her schoolwork. She says she would consider resuming psychotherapy.

At this point, Ms. F’s anxiety is significantly improved based on clinical impression. She continues to do well 6 months after stopping psychotherapy, though she is still without a boyfriend.

poll hereTable 2

Autism or Asperger’s? Watch for these distinguishing features

The authors’ observations

The ability to possess a theory of mind—or “mentalize”—helps us understand others’ beliefs, desires, thoughts, intentions, and knowledge. Attributing mental states to self and others helps explain and predict behavior, which is critical to social interaction.

A therapeutic relationship can help teach patients to handle social situations.⁴ In autism or PDD,^5,6 however, theory of mind deficits typically frustrate relationship building.⁴ Because ability to mentalize is critical to psychodynamic psychotherapy,⁷ exploration does not help patients with PDD. By contrast, therapists can be more successful by being active in sessions and giving directions, suggestions, and information.

Which psychotherapy models work? Limited data address psychotherapy for adults with PDD; most studies have followed children.

CBT for persons with autism or PDD is directive, problem-focused, and targets automatic reactions.⁸ Social skills groups and CBT focusing on day-to-day problem solving can help older children and adolescents.⁹ A 20-week social skills intervention employing a CBT approach, paired with psychoeducation for parents, has helped boys ages 8 to 12 with autism, PDD, or Asperger’s syndrome.¹⁰

Other interventions use pictures, cartoons, and other visuals to help patients identify and correct misperceptions and determine how different responses might affect people’s thoughts and feelings.^9,11 Role play allows the patient to practice social interaction but requires make-believe,¹¹ so getting a PDD patient to participate can be challenging.

Medication can help manage comorbid anxiety, obsessive-compulsive, and mood symptoms in PDD. Limited data support using selective serotonin reuptake inhibitors for this purpose.¹²

Related resources

• Ozonoff S, Dawson G, McPartland J. A parent’s guide to Asperger syndrome & high-functioning autism: how to meet the challenges and help your child thrive. New York: Guilford Press; 2002.
  
• MAAP Services. A global information and support network for more advanced persons with autism and Asperger syndrome. www.asperger.org.
  

• Escitalopram • Lexapro
  

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

History: a lovelorn life

Ms. F, age 33, presents with one complaint: “I want to know how to maintain a relationship.” Problem is, social situations have made her feel anxious since childhood. She has trouble keeping a boyfriend; she left two intimate, extended relationships at different times.

She says she is too ashamed to invite people over because she cannot keep her apartment neat. She is also sick of her job as a filing clerk and wants a new career.

Ms. F reports no other anxiety symptoms or mood changes but often cannot concentrate. She denies impulsivity or poor judgment but admits that she makes decisions without getting important facts. For example, she enrolled at a community college without knowing what skills her new career would require. About 6 months ago, she left her boyfriend after realizing—18 months into the relationship—that he does not share her interests.

poll here

The authors’ observations

Information on all the above factors is crucial to diagnosing a socialization problem. Outline your differential diagnosis as the interview progresses.

Ask the patient:

How did you fare in school? A childhood history of pervasive inattention or impulsivity in at least two settings (at home and in school, for example) can signal attention-deficit/hyperactivity disorder (ADHD).^{fragile X syndrome). Boys with the fragile X premutation have a higher rate of ADHD symptoms and autism spectrum disorders than do boys without this premutation.3 Ms. F’s test showed two normal alleles, thus ruling out fragile X premutation.}

Table 1

Mental status examination signs that suggest a PDD

Treatment: medication and exploration

Ms. F agrees to an ADOS test. Her total score of 9 (7 in social, 2 in communication, and 0 in stereotyped/repetitive behavior) suggest a moderate PDD. We rule out autism based on the test score and Asperger’s syndrome because of her early language development delays (Table 2).

We start escitalopram, 10 mg/d, to address Ms. F’s anxiety. We see her weekly for medication management and start weekly psychotherapy to explore her two previous relationships and her desire to find a partner.

Ms. F, however, reacts anxiously to the therapist’s exploratory techniques. She has difficulty taking the lead and becomes extremely uncomfortable with silences in the conversation. The therapist tries cognitive-behavioral tactics to engage her, but Ms. F does not respond.

The therapist then conceptualizes her role as “coach” and tries a more-direct, problem-solving approach. She addresses specific challenges, such as an overwhelming class assignment, but Ms. F does not discuss or follow through on the problem.

After 6 months, Ms. F asks to stop psychotherapy because she has made little progress. She also asks to reduce medication checks to monthly, saying that weekly sessions interfere with her schoolwork. She says she would consider resuming psychotherapy.

At this point, Ms. F’s anxiety is significantly improved based on clinical impression. She continues to do well 6 months after stopping psychotherapy, though she is still without a boyfriend.

poll hereTable 2

Autism or Asperger’s? Watch for these distinguishing features

The authors’ observations

The ability to possess a theory of mind—or “mentalize”—helps us understand others’ beliefs, desires, thoughts, intentions, and knowledge. Attributing mental states to self and others helps explain and predict behavior, which is critical to social interaction.

A therapeutic relationship can help teach patients to handle social situations.⁴ In autism or PDD,^5,6 however, theory of mind deficits typically frustrate relationship building.⁴ Because ability to mentalize is critical to psychodynamic psychotherapy,⁷ exploration does not help patients with PDD. By contrast, therapists can be more successful by being active in sessions and giving directions, suggestions, and information.

Which psychotherapy models work? Limited data address psychotherapy for adults with PDD; most studies have followed children.

CBT for persons with autism or PDD is directive, problem-focused, and targets automatic reactions.⁸ Social skills groups and CBT focusing on day-to-day problem solving can help older children and adolescents.⁹ A 20-week social skills intervention employing a CBT approach, paired with psychoeducation for parents, has helped boys ages 8 to 12 with autism, PDD, or Asperger’s syndrome.¹⁰

Other interventions use pictures, cartoons, and other visuals to help patients identify and correct misperceptions and determine how different responses might affect people’s thoughts and feelings.^9,11 Role play allows the patient to practice social interaction but requires make-believe,¹¹ so getting a PDD patient to participate can be challenging.

Medication can help manage comorbid anxiety, obsessive-compulsive, and mood symptoms in PDD. Limited data support using selective serotonin reuptake inhibitors for this purpose.¹²

Related resources

• Ozonoff S, Dawson G, McPartland J. A parent’s guide to Asperger syndrome & high-functioning autism: how to meet the challenges and help your child thrive. New York: Guilford Press; 2002.
  
• MAAP Services. A global information and support network for more advanced persons with autism and Asperger syndrome. www.asperger.org.
  

• Escitalopram • Lexapro
  

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

History: a lovelorn life

Ms. F, age 33, presents with one complaint: “I want to know how to maintain a relationship.” Problem is, social situations have made her feel anxious since childhood. She has trouble keeping a boyfriend; she left two intimate, extended relationships at different times.

She says she is too ashamed to invite people over because she cannot keep her apartment neat. She is also sick of her job as a filing clerk and wants a new career.

Ms. F reports no other anxiety symptoms or mood changes but often cannot concentrate. She denies impulsivity or poor judgment but admits that she makes decisions without getting important facts. For example, she enrolled at a community college without knowing what skills her new career would require. About 6 months ago, she left her boyfriend after realizing—18 months into the relationship—that he does not share her interests.

poll here

The authors’ observations

Information on all the above factors is crucial to diagnosing a socialization problem. Outline your differential diagnosis as the interview progresses.

Ask the patient:

How did you fare in school? A childhood history of pervasive inattention or impulsivity in at least two settings (at home and in school, for example) can signal attention-deficit/hyperactivity disorder (ADHD).^{fragile X syndrome). Boys with the fragile X premutation have a higher rate of ADHD symptoms and autism spectrum disorders than do boys without this premutation.3 Ms. F’s test showed two normal alleles, thus ruling out fragile X premutation.}

Table 1

Mental status examination signs that suggest a PDD

Treatment: medication and exploration

Ms. F agrees to an ADOS test. Her total score of 9 (7 in social, 2 in communication, and 0 in stereotyped/repetitive behavior) suggest a moderate PDD. We rule out autism based on the test score and Asperger’s syndrome because of her early language development delays (Table 2).

We start escitalopram, 10 mg/d, to address Ms. F’s anxiety. We see her weekly for medication management and start weekly psychotherapy to explore her two previous relationships and her desire to find a partner.

Ms. F, however, reacts anxiously to the therapist’s exploratory techniques. She has difficulty taking the lead and becomes extremely uncomfortable with silences in the conversation. The therapist tries cognitive-behavioral tactics to engage her, but Ms. F does not respond.

The therapist then conceptualizes her role as “coach” and tries a more-direct, problem-solving approach. She addresses specific challenges, such as an overwhelming class assignment, but Ms. F does not discuss or follow through on the problem.

After 6 months, Ms. F asks to stop psychotherapy because she has made little progress. She also asks to reduce medication checks to monthly, saying that weekly sessions interfere with her schoolwork. She says she would consider resuming psychotherapy.

At this point, Ms. F’s anxiety is significantly improved based on clinical impression. She continues to do well 6 months after stopping psychotherapy, though she is still without a boyfriend.

poll hereTable 2

Autism or Asperger’s? Watch for these distinguishing features

The authors’ observations

The ability to possess a theory of mind—or “mentalize”—helps us understand others’ beliefs, desires, thoughts, intentions, and knowledge. Attributing mental states to self and others helps explain and predict behavior, which is critical to social interaction.

A therapeutic relationship can help teach patients to handle social situations.⁴ In autism or PDD,^5,6 however, theory of mind deficits typically frustrate relationship building.⁴ Because ability to mentalize is critical to psychodynamic psychotherapy,⁷ exploration does not help patients with PDD. By contrast, therapists can be more successful by being active in sessions and giving directions, suggestions, and information.

Which psychotherapy models work? Limited data address psychotherapy for adults with PDD; most studies have followed children.

CBT for persons with autism or PDD is directive, problem-focused, and targets automatic reactions.⁸ Social skills groups and CBT focusing on day-to-day problem solving can help older children and adolescents.⁹ A 20-week social skills intervention employing a CBT approach, paired with psychoeducation for parents, has helped boys ages 8 to 12 with autism, PDD, or Asperger’s syndrome.¹⁰

Other interventions use pictures, cartoons, and other visuals to help patients identify and correct misperceptions and determine how different responses might affect people’s thoughts and feelings.^9,11 Role play allows the patient to practice social interaction but requires make-believe,¹¹ so getting a PDD patient to participate can be challenging.

Medication can help manage comorbid anxiety, obsessive-compulsive, and mood symptoms in PDD. Limited data support using selective serotonin reuptake inhibitors for this purpose.¹²

Related resources

• Ozonoff S, Dawson G, McPartland J. A parent’s guide to Asperger syndrome & high-functioning autism: how to meet the challenges and help your child thrive. New York: Guilford Press; 2002.
  
• MAAP Services. A global information and support network for more advanced persons with autism and Asperger syndrome. www.asperger.org.
  

• Escitalopram • Lexapro
  

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Psychotropics^1,2 are used to manage maladaptive and interfering behaviors in 70% of patients with fragile X syndrome (FXS), the leading cause of hereditary mental retardation. Treatment tends to follow a developmental course:

• In children, stimulants and alpha-2 agonists are used for attention-deficit/hyperactivity disorder (ADHD)-like symptoms.
  
• In adolescents and adults, selective serotonin reuptake inhibitors (SSRIs) are used for anxiety/repetitive phenomena and second-generation antipsychotics (SGAs) for irritability.
  

This course—which is often effective—is based primarily on anecdotal descriptions and on rationales borrowed from studies of ADHD, obsessive-compulsive disorder (OCD), and autistic disorder/related pervasive developmental disorders (PDDs).³ Disease-modifying agents to target the underlying brain dysregulation inherent in FXS (Box)^1,4-10 are being investigated. For now, psychotropics can help you manage three common FXS symptom clusters: inattention and hyperactivity, anxiety, and aggression and self-injurious behavior (SIB).

Box

Table 1

Clinical characteristics of patients with fragile X syndrome

Inattention and hyperactivity

Mike, age 6, has fragile X syndrome. He has been attending first grade for 4 months, and his teacher reports he does not sit still, runs throughout the classroom, and cannot focus on class work. Mike’s hyperactivity has been evident for 2 years but did not cause problems until first grade, his parents report.

Psychostimulants are the most frequently prescribed agents for inattention and hyperactivity in FXS, particularly in boys and male adolescents.¹ Among FXS patients prescribed ≥ 1 psychotropic, approximately 70% are taking a stimulant.^1,2

Efficacy. A clinical chart review found a 75% response rate in FXS children and adolescents who were given a stimulant for inattention and/or hyperactivity.¹ This is higher than the 25% to 49% stimulant response rate reported in patients with PDDs.^11,12

A 3-week, placebo-controlled, crossover trial of methylphenidate and dextroamphetamine noted a statistically significant response only to methylphenidate, with a positive response reported in 10 of 15 children (67%).¹³

Side effects. To date, limited information has described the rate of intolerable side effects associated with stimulant use in FXS,¹⁴ but in patients with PDD:

• 154 of 268 (57.5%) patient trials in a retrospective naturalistic study showed significant adverse effects with stimulant use.¹¹
  
• 13 of 72 (18%) subjects in a controlled trial discontinued methylphenidate because of adverse events (most commonly irritability).¹²
  

Antiadrenergics. The alpha-2 agonists clonidine and guanfacine are the second most-used class of agents for inattention and hyperactivity in FXS. As with stimulants, boys and male adolescents are most likely to receive alpha-2 agonists, with administration rates of 10% to 20%.^1,2

Efficacy. In one survey, nearly two-thirds (63%) of parents described clonidine as “very beneficial” to 35 children (mean age 6.6) with FXS.¹⁵ This is similar to a 70% response rate described for these alpha-2 agonists in a chart review.¹ These rates are much higher than the 24% response rate reported with guanfacine in a retrospective chart review of 80 children and adolescents with a PDD.¹⁶ In that review, guanfacine use was associated with reduced hyperactivity, insomnia, and tics, and increased attention.¹⁵

Side effects associated with alpha-2 agonists include lowered blood pressure and sedation.

L-acetylcarnitine—a carnitine derivative required for neuronal use and transport of fatty acids—is being investigated to treat hyperactivity in FXS. Hyperactive symptoms improved significantly with L-acetylcarnitine, as measured by the Conners’ Abbreviated Parent-Teacher Questionnaire, in a 1-year, placebo-controlled trial of 20 boys (mean age 9.2) with FXS.¹⁷

Discussion. Supporting evidence is limited, but clinicians are treating ADHD-like symptoms with stimulants and alpha-2 agonists in many FXS patients. Preliminary data indicate that stimulants may be more effective and better tolerated in individuals with FXS than in those with PDD.

Trying a stimulant or alpha-2 agonist for inattention or hyperactivity symptoms in a child or adolescent with FXS appears clinically appropriate, given the available evidence. Additional data based on placebo-controlled and standardized measures of treatment response are needed to help guide treatment.

We start Mike on methylphenidate, 5 mg in the morning, for inattention and hyperactivity. He tolerates this well, and after 2 weeks we increase the dosage to 5 mg bid. Several weeks into treatment, his teacher comments that he is beginning to stay in his seat and attends to some assigned tasks in the classroom.

Mike continued to tolerate methylphenidate over the next 4 years. We gradually increased the dosage as he grew and when he periodically developed breakthrough interfering symptoms in the classroom.

Anxiety symptoms

In grade school, Mike became increasingly nervous around schoolmates, teachers, and friends. His teachers commented that he repeated phrases when he appeared anxious. Other children in his special education class began to shun him; they found his perseveration odd and sometimes threatening.

Now that Mike is age 10 and in fifth grade, his parents decide that his anxiety, particularly in social settings, is interfering with his life.

Anxiety symptoms—including generalized nervousness and OCD-like obsessions and perseverations—are common psychotropic targets in FXS. Boys may be the FXS patients most often prescribed drugs for inattention and hyperactivity, but they are the least likely to receive antidepressants for anxiety symptoms.^1,2

Efficacy. More than 50% of female patients and men with FXS are prescribed SSRIs for anxiety (Table 2), and the reported response rate of 50% to 60%¹ is similar to that seen with SSRIs in autism and related disorders.¹⁸ In autism, a developmental approach is warranted, as SSRIs tend to be less effective and cause more side effects in children and adolescents than in adults.¹⁸

Adverse effects reported with SSRIs in FXS include behavioral activation, appetite changes, insomnia, and nausea.¹ In a study of fluoxetine for FXS symptoms, 10 of 35 patients (29%) had persistent side effects, most commonly weight loss and weight gain.¹⁹ One patient with pre-existing suicidal ideation worsened.

Watch for emergence or worsening of suicidal thoughts in all children and adolescents receiving antidepressants, whatever their target symptoms.

Mike is taking methylphenidate, 15 mg bid, for comorbid ADHD, and we add fluoxetine, 10 mg/d, for anxiety. This regimen is well-tolerated, so we increase fluoxetine to 20 mg/d at his 4-week follow-up appointment. After about 8 weeks, Mike’s parents report that his anxiety-associated symptoms are less severe.

Mike still appears nervous sometimes, but he uses markedly fewer perseverative phrases. This allows him to interact more meaningfully with peers and contributes to his social development.

Table 2

Target symptoms and treatment options for fragile X syndrome

Aggression and self-injury

Mike, now age 20 and participating daily in a vocational workshop, begins yelling profanities at coworkers. At his group home, he has been hitting staff at least twice a week when redirected.

He is no longer taking stimulants, having been weaned from methylphenidate several years ago, but he continues to take fluoxetine, 40 mg/d.

Fluoxetine¹⁹ and clonidine¹⁵ can decrease irritability in FXS, but atypical antipsychotics are most commonly used for aggression and SIB.^1,2 SGAs are prescribed to 10% to 20% of FXS patients who are taking medication^1,2—particularly to men—and have produced response rates of 60% to 100% when used for aggression and SIB.¹

Risperidone. No published reports have addressed using specific SGAs in FXS. In the PDD literature, most controlled data concerns risperidone.²⁰

The largest randomized, placebo-controlled trial enrolled 101 children ages 5 to 17 with autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior. Among the 49 children taking risperidone, 0.5 to 3.5 mg/d for 8 weeks, 34 (69%) were judged as treatment responders with significantly reduced irritable behavior, compared with 6 of 52 (12%) taking placebo.²¹ Risperidone therapy was associated with average weight gain of 2.7±2.9 kg, compared with 0.8±2.2 kg with placebo.

Besides weight gain, other significant side effects associated with risperidone include sedation and elevated serum prolactin. These effects often are more pronounced in children and adolescents than in adults with PDDs.²⁰

Other antipsychotics. Future use of SGAs in FXS will likely mirror the pattern seen in PDDs, where clinicians are moving towards weight-neutral antipsychotics such as ziprasidone and aripiprazole. In a preliminary report, aripiprazole reduced irritability in 5 youths with PDD.²² Our group is conducting a double-blind, placebo-controlled trial of aripiprazole in autism, targeting aggression, SIB, and irritability.

Discussion. SGAs are used most often in FXS to treat aggression and SIB, based on data from studies on treating similar symptoms in PDDs. Closely monitor patients for sedation, weight gain, and lipid, glucose, and prolactin elevations when using SGAs (Table 3). Be especially vigilant when children gain weight rapidly or show hyperprolactinemia signs while taking these drugs.

After being suspended from the vocational workshop, Mike is treated at a local mental health center for aggressive behaviors. He tolerates an initial dosage of aripiprazole,2.5 mg/d, which is titrated in 2.5-mg increments biweekly to 10 mg/d. At this dosage, he stops hitting staff members and his yelling of profanities is greatly reduced. Over several months, Mike returns to his vocational workshop and maintains residence at his group home.

Table 3

Medication side effects and recommended monitoring

Genetic-related treatments

Studies are needed to investigate the use of stimulants, SSRIs, and antipsychotics in patients with FXS unaccompanied by generalized anxiety disorder, OCD, ADHD, or PDDs. How FXS patients without those comorbidities will respond to drug treatment is unknown. Also, little also is known about possible side effects associated with combining drug treatments in individuals with FXS.

Future drug treatment in FXS will likely focus on agents that target the underlying neurochemical dysregulation associated with the FXS genotype. This approach might reduce interfering behaviors and alter the course of cognitive dysfunction—including mental retardation—associated with FXS.

Past attempts to correct FXS’ neurochemical abnormalities focused on using folic acid. The term “fragile X” describes how the X chromosome of individuals with FXS fractures in a folate-deprived medium. Many controlled trials of folic acid in FXS did not support earlier positive reports, however.⁴

Greater understanding of fragile X mental retardation protein (FMRP) function has led to the metabotropic glutamate receptor (mGluR) theory.⁷ It holds that FMRP underproduction allows exaggerated group 1 mGluR activity and leads to the FXS neurobehavioral phenotype. Researchers now are attempting to reverse the neurochemical impact of insufficient FMRP with two medication classes:

• selective group 1 mGluR receptor antagonists (mGluR5 antagonists, in particular). The mGluR5 receptor antagonist MPEP has shown the ability to rescue normal behaviors in animal models of FXS. MPEP and lithium have reversed behaviors associated with FXS and—at the microscopic level—rescued synaptic plasticity.^23,24 In the drosophila fly model of FXS, lithium reduced activity in the mGluR cascade, thus compensating for lack of FMRP.²³
  
• positive AMPA receptor modulators (ampakines) that promote activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.⁹ Excessive mGluR activity appears to impair AMPA receptors’ ability to promote cortical development, memory, and learning.⁷ Reduced AMPA receptors have been shown in the FXS mouse model,²⁵ and an ampakine is being investigated in a study of men with FXS and autism.¹
  

• FRAXA: The Fragile X Research Foundation. Founded by parents of children with fragile X syndrome to increase funding for research toward effective treatments. www.fraxa.org.
  
• The National Fragile X Foundation. Provides educational and emotional support for fragile X families and promotes public and professional awareness. www.fragilex.org.
  
• Hagerman RJ, Hagerman PJ, eds. Fragile X syndrome: diagnosis, treatment, and research, 3rd ed. Baltimore, MD: The Johns Hopkins University Press; 2002.
  

• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine • Dexedrine
  
• Fluoxetine • Prozac
  
• Guanfacine • Tenex
  
• Lithium • Eskalith, Lithobid
  
• Methylphenidate • Ritalin
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

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

Dr. Stigler receives grant/research support from Bristol-Myers Squibb Co. and Janssen Pharmaceutica.

Dr. Posey receives grant/research support from Forest Pharmaceuticals and Janssen Pharmaceutica and is a consultant to Forest Pharmaceuticals.

Dr. McDougle receives grant/research support from Forest Pharmaceuticals, Janssen Pharmaceutica, Bristol-Myers Squibb Co., and Eli Lilly and Co., and is a consultant to or speaker for Forest Pharmaceuticals, Janssen Pharmaceutica, Bristol-Myers Squibb Co., Eli Lilly and Co., and Pfizer Inc.

Psychotropics^1,2 are used to manage maladaptive and interfering behaviors in 70% of patients with fragile X syndrome (FXS), the leading cause of hereditary mental retardation. Treatment tends to follow a developmental course:

• In children, stimulants and alpha-2 agonists are used for attention-deficit/hyperactivity disorder (ADHD)-like symptoms.
  
• In adolescents and adults, selective serotonin reuptake inhibitors (SSRIs) are used for anxiety/repetitive phenomena and second-generation antipsychotics (SGAs) for irritability.
  

This course—which is often effective—is based primarily on anecdotal descriptions and on rationales borrowed from studies of ADHD, obsessive-compulsive disorder (OCD), and autistic disorder/related pervasive developmental disorders (PDDs).³ Disease-modifying agents to target the underlying brain dysregulation inherent in FXS (Box)^1,4-10 are being investigated. For now, psychotropics can help you manage three common FXS symptom clusters: inattention and hyperactivity, anxiety, and aggression and self-injurious behavior (SIB).

Box

Table 1

Clinical characteristics of patients with fragile X syndrome

Inattention and hyperactivity

Mike, age 6, has fragile X syndrome. He has been attending first grade for 4 months, and his teacher reports he does not sit still, runs throughout the classroom, and cannot focus on class work. Mike’s hyperactivity has been evident for 2 years but did not cause problems until first grade, his parents report.

Psychostimulants are the most frequently prescribed agents for inattention and hyperactivity in FXS, particularly in boys and male adolescents.¹ Among FXS patients prescribed ≥ 1 psychotropic, approximately 70% are taking a stimulant.^1,2

Efficacy. A clinical chart review found a 75% response rate in FXS children and adolescents who were given a stimulant for inattention and/or hyperactivity.¹ This is higher than the 25% to 49% stimulant response rate reported in patients with PDDs.^11,12

A 3-week, placebo-controlled, crossover trial of methylphenidate and dextroamphetamine noted a statistically significant response only to methylphenidate, with a positive response reported in 10 of 15 children (67%).¹³

Side effects. To date, limited information has described the rate of intolerable side effects associated with stimulant use in FXS,¹⁴ but in patients with PDD:

• 154 of 268 (57.5%) patient trials in a retrospective naturalistic study showed significant adverse effects with stimulant use.¹¹
  
• 13 of 72 (18%) subjects in a controlled trial discontinued methylphenidate because of adverse events (most commonly irritability).¹²
  

Antiadrenergics. The alpha-2 agonists clonidine and guanfacine are the second most-used class of agents for inattention and hyperactivity in FXS. As with stimulants, boys and male adolescents are most likely to receive alpha-2 agonists, with administration rates of 10% to 20%.^1,2

Efficacy. In one survey, nearly two-thirds (63%) of parents described clonidine as “very beneficial” to 35 children (mean age 6.6) with FXS.¹⁵ This is similar to a 70% response rate described for these alpha-2 agonists in a chart review.¹ These rates are much higher than the 24% response rate reported with guanfacine in a retrospective chart review of 80 children and adolescents with a PDD.¹⁶ In that review, guanfacine use was associated with reduced hyperactivity, insomnia, and tics, and increased attention.¹⁵

Side effects associated with alpha-2 agonists include lowered blood pressure and sedation.

L-acetylcarnitine—a carnitine derivative required for neuronal use and transport of fatty acids—is being investigated to treat hyperactivity in FXS. Hyperactive symptoms improved significantly with L-acetylcarnitine, as measured by the Conners’ Abbreviated Parent-Teacher Questionnaire, in a 1-year, placebo-controlled trial of 20 boys (mean age 9.2) with FXS.¹⁷

Discussion. Supporting evidence is limited, but clinicians are treating ADHD-like symptoms with stimulants and alpha-2 agonists in many FXS patients. Preliminary data indicate that stimulants may be more effective and better tolerated in individuals with FXS than in those with PDD.

Trying a stimulant or alpha-2 agonist for inattention or hyperactivity symptoms in a child or adolescent with FXS appears clinically appropriate, given the available evidence. Additional data based on placebo-controlled and standardized measures of treatment response are needed to help guide treatment.

We start Mike on methylphenidate, 5 mg in the morning, for inattention and hyperactivity. He tolerates this well, and after 2 weeks we increase the dosage to 5 mg bid. Several weeks into treatment, his teacher comments that he is beginning to stay in his seat and attends to some assigned tasks in the classroom.

Mike continued to tolerate methylphenidate over the next 4 years. We gradually increased the dosage as he grew and when he periodically developed breakthrough interfering symptoms in the classroom.

Anxiety symptoms

In grade school, Mike became increasingly nervous around schoolmates, teachers, and friends. His teachers commented that he repeated phrases when he appeared anxious. Other children in his special education class began to shun him; they found his perseveration odd and sometimes threatening.

Now that Mike is age 10 and in fifth grade, his parents decide that his anxiety, particularly in social settings, is interfering with his life.

Anxiety symptoms—including generalized nervousness and OCD-like obsessions and perseverations—are common psychotropic targets in FXS. Boys may be the FXS patients most often prescribed drugs for inattention and hyperactivity, but they are the least likely to receive antidepressants for anxiety symptoms.^1,2

Efficacy. More than 50% of female patients and men with FXS are prescribed SSRIs for anxiety (Table 2), and the reported response rate of 50% to 60%¹ is similar to that seen with SSRIs in autism and related disorders.¹⁸ In autism, a developmental approach is warranted, as SSRIs tend to be less effective and cause more side effects in children and adolescents than in adults.¹⁸

Adverse effects reported with SSRIs in FXS include behavioral activation, appetite changes, insomnia, and nausea.¹ In a study of fluoxetine for FXS symptoms, 10 of 35 patients (29%) had persistent side effects, most commonly weight loss and weight gain.¹⁹ One patient with pre-existing suicidal ideation worsened.

Watch for emergence or worsening of suicidal thoughts in all children and adolescents receiving antidepressants, whatever their target symptoms.

Mike is taking methylphenidate, 15 mg bid, for comorbid ADHD, and we add fluoxetine, 10 mg/d, for anxiety. This regimen is well-tolerated, so we increase fluoxetine to 20 mg/d at his 4-week follow-up appointment. After about 8 weeks, Mike’s parents report that his anxiety-associated symptoms are less severe.

Mike still appears nervous sometimes, but he uses markedly fewer perseverative phrases. This allows him to interact more meaningfully with peers and contributes to his social development.

Table 2

Target symptoms and treatment options for fragile X syndrome

Aggression and self-injury

Mike, now age 20 and participating daily in a vocational workshop, begins yelling profanities at coworkers. At his group home, he has been hitting staff at least twice a week when redirected.

He is no longer taking stimulants, having been weaned from methylphenidate several years ago, but he continues to take fluoxetine, 40 mg/d.

Fluoxetine¹⁹ and clonidine¹⁵ can decrease irritability in FXS, but atypical antipsychotics are most commonly used for aggression and SIB.^1,2 SGAs are prescribed to 10% to 20% of FXS patients who are taking medication^1,2—particularly to men—and have produced response rates of 60% to 100% when used for aggression and SIB.¹

Risperidone. No published reports have addressed using specific SGAs in FXS. In the PDD literature, most controlled data concerns risperidone.²⁰

The largest randomized, placebo-controlled trial enrolled 101 children ages 5 to 17 with autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior. Among the 49 children taking risperidone, 0.5 to 3.5 mg/d for 8 weeks, 34 (69%) were judged as treatment responders with significantly reduced irritable behavior, compared with 6 of 52 (12%) taking placebo.²¹ Risperidone therapy was associated with average weight gain of 2.7±2.9 kg, compared with 0.8±2.2 kg with placebo.

Besides weight gain, other significant side effects associated with risperidone include sedation and elevated serum prolactin. These effects often are more pronounced in children and adolescents than in adults with PDDs.²⁰

Other antipsychotics. Future use of SGAs in FXS will likely mirror the pattern seen in PDDs, where clinicians are moving towards weight-neutral antipsychotics such as ziprasidone and aripiprazole. In a preliminary report, aripiprazole reduced irritability in 5 youths with PDD.²² Our group is conducting a double-blind, placebo-controlled trial of aripiprazole in autism, targeting aggression, SIB, and irritability.

Discussion. SGAs are used most often in FXS to treat aggression and SIB, based on data from studies on treating similar symptoms in PDDs. Closely monitor patients for sedation, weight gain, and lipid, glucose, and prolactin elevations when using SGAs (Table 3). Be especially vigilant when children gain weight rapidly or show hyperprolactinemia signs while taking these drugs.

After being suspended from the vocational workshop, Mike is treated at a local mental health center for aggressive behaviors. He tolerates an initial dosage of aripiprazole,2.5 mg/d, which is titrated in 2.5-mg increments biweekly to 10 mg/d. At this dosage, he stops hitting staff members and his yelling of profanities is greatly reduced. Over several months, Mike returns to his vocational workshop and maintains residence at his group home.

Table 3

Medication side effects and recommended monitoring

Genetic-related treatments

Studies are needed to investigate the use of stimulants, SSRIs, and antipsychotics in patients with FXS unaccompanied by generalized anxiety disorder, OCD, ADHD, or PDDs. How FXS patients without those comorbidities will respond to drug treatment is unknown. Also, little also is known about possible side effects associated with combining drug treatments in individuals with FXS.

Future drug treatment in FXS will likely focus on agents that target the underlying neurochemical dysregulation associated with the FXS genotype. This approach might reduce interfering behaviors and alter the course of cognitive dysfunction—including mental retardation—associated with FXS.

Past attempts to correct FXS’ neurochemical abnormalities focused on using folic acid. The term “fragile X” describes how the X chromosome of individuals with FXS fractures in a folate-deprived medium. Many controlled trials of folic acid in FXS did not support earlier positive reports, however.⁴

Greater understanding of fragile X mental retardation protein (FMRP) function has led to the metabotropic glutamate receptor (mGluR) theory.⁷ It holds that FMRP underproduction allows exaggerated group 1 mGluR activity and leads to the FXS neurobehavioral phenotype. Researchers now are attempting to reverse the neurochemical impact of insufficient FMRP with two medication classes:

• selective group 1 mGluR receptor antagonists (mGluR5 antagonists, in particular). The mGluR5 receptor antagonist MPEP has shown the ability to rescue normal behaviors in animal models of FXS. MPEP and lithium have reversed behaviors associated with FXS and—at the microscopic level—rescued synaptic plasticity.^23,24 In the drosophila fly model of FXS, lithium reduced activity in the mGluR cascade, thus compensating for lack of FMRP.²³
  
• positive AMPA receptor modulators (ampakines) that promote activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.⁹ Excessive mGluR activity appears to impair AMPA receptors’ ability to promote cortical development, memory, and learning.⁷ Reduced AMPA receptors have been shown in the FXS mouse model,²⁵ and an ampakine is being investigated in a study of men with FXS and autism.¹
  

• FRAXA: The Fragile X Research Foundation. Founded by parents of children with fragile X syndrome to increase funding for research toward effective treatments. www.fraxa.org.
  
• The National Fragile X Foundation. Provides educational and emotional support for fragile X families and promotes public and professional awareness. www.fragilex.org.
  
• Hagerman RJ, Hagerman PJ, eds. Fragile X syndrome: diagnosis, treatment, and research, 3rd ed. Baltimore, MD: The Johns Hopkins University Press; 2002.
  

• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine • Dexedrine
  
• Fluoxetine • Prozac
  
• Guanfacine • Tenex
  
• Lithium • Eskalith, Lithobid
  
• Methylphenidate • Ritalin
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

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

Dr. Stigler receives grant/research support from Bristol-Myers Squibb Co. and Janssen Pharmaceutica.

Dr. Posey receives grant/research support from Forest Pharmaceuticals and Janssen Pharmaceutica and is a consultant to Forest Pharmaceuticals.

Dr. McDougle receives grant/research support from Forest Pharmaceuticals, Janssen Pharmaceutica, Bristol-Myers Squibb Co., and Eli Lilly and Co., and is a consultant to or speaker for Forest Pharmaceuticals, Janssen Pharmaceutica, Bristol-Myers Squibb Co., Eli Lilly and Co., and Pfizer Inc.

Psychotropics^1,2 are used to manage maladaptive and interfering behaviors in 70% of patients with fragile X syndrome (FXS), the leading cause of hereditary mental retardation. Treatment tends to follow a developmental course:

• In children, stimulants and alpha-2 agonists are used for attention-deficit/hyperactivity disorder (ADHD)-like symptoms.
  
• In adolescents and adults, selective serotonin reuptake inhibitors (SSRIs) are used for anxiety/repetitive phenomena and second-generation antipsychotics (SGAs) for irritability.
  

This course—which is often effective—is based primarily on anecdotal descriptions and on rationales borrowed from studies of ADHD, obsessive-compulsive disorder (OCD), and autistic disorder/related pervasive developmental disorders (PDDs).³ Disease-modifying agents to target the underlying brain dysregulation inherent in FXS (Box)^1,4-10 are being investigated. For now, psychotropics can help you manage three common FXS symptom clusters: inattention and hyperactivity, anxiety, and aggression and self-injurious behavior (SIB).

Box

Table 1

Clinical characteristics of patients with fragile X syndrome

Inattention and hyperactivity

Mike, age 6, has fragile X syndrome. He has been attending first grade for 4 months, and his teacher reports he does not sit still, runs throughout the classroom, and cannot focus on class work. Mike’s hyperactivity has been evident for 2 years but did not cause problems until first grade, his parents report.

Psychostimulants are the most frequently prescribed agents for inattention and hyperactivity in FXS, particularly in boys and male adolescents.¹ Among FXS patients prescribed ≥ 1 psychotropic, approximately 70% are taking a stimulant.^1,2

Efficacy. A clinical chart review found a 75% response rate in FXS children and adolescents who were given a stimulant for inattention and/or hyperactivity.¹ This is higher than the 25% to 49% stimulant response rate reported in patients with PDDs.^11,12

A 3-week, placebo-controlled, crossover trial of methylphenidate and dextroamphetamine noted a statistically significant response only to methylphenidate, with a positive response reported in 10 of 15 children (67%).¹³

Side effects. To date, limited information has described the rate of intolerable side effects associated with stimulant use in FXS,¹⁴ but in patients with PDD:

• 154 of 268 (57.5%) patient trials in a retrospective naturalistic study showed significant adverse effects with stimulant use.¹¹
  
• 13 of 72 (18%) subjects in a controlled trial discontinued methylphenidate because of adverse events (most commonly irritability).¹²
  

Antiadrenergics. The alpha-2 agonists clonidine and guanfacine are the second most-used class of agents for inattention and hyperactivity in FXS. As with stimulants, boys and male adolescents are most likely to receive alpha-2 agonists, with administration rates of 10% to 20%.^1,2

Efficacy. In one survey, nearly two-thirds (63%) of parents described clonidine as “very beneficial” to 35 children (mean age 6.6) with FXS.¹⁵ This is similar to a 70% response rate described for these alpha-2 agonists in a chart review.¹ These rates are much higher than the 24% response rate reported with guanfacine in a retrospective chart review of 80 children and adolescents with a PDD.¹⁶ In that review, guanfacine use was associated with reduced hyperactivity, insomnia, and tics, and increased attention.¹⁵

Side effects associated with alpha-2 agonists include lowered blood pressure and sedation.

L-acetylcarnitine—a carnitine derivative required for neuronal use and transport of fatty acids—is being investigated to treat hyperactivity in FXS. Hyperactive symptoms improved significantly with L-acetylcarnitine, as measured by the Conners’ Abbreviated Parent-Teacher Questionnaire, in a 1-year, placebo-controlled trial of 20 boys (mean age 9.2) with FXS.¹⁷

Discussion. Supporting evidence is limited, but clinicians are treating ADHD-like symptoms with stimulants and alpha-2 agonists in many FXS patients. Preliminary data indicate that stimulants may be more effective and better tolerated in individuals with FXS than in those with PDD.

Trying a stimulant or alpha-2 agonist for inattention or hyperactivity symptoms in a child or adolescent with FXS appears clinically appropriate, given the available evidence. Additional data based on placebo-controlled and standardized measures of treatment response are needed to help guide treatment.

We start Mike on methylphenidate, 5 mg in the morning, for inattention and hyperactivity. He tolerates this well, and after 2 weeks we increase the dosage to 5 mg bid. Several weeks into treatment, his teacher comments that he is beginning to stay in his seat and attends to some assigned tasks in the classroom.

Mike continued to tolerate methylphenidate over the next 4 years. We gradually increased the dosage as he grew and when he periodically developed breakthrough interfering symptoms in the classroom.

Anxiety symptoms

In grade school, Mike became increasingly nervous around schoolmates, teachers, and friends. His teachers commented that he repeated phrases when he appeared anxious. Other children in his special education class began to shun him; they found his perseveration odd and sometimes threatening.

Now that Mike is age 10 and in fifth grade, his parents decide that his anxiety, particularly in social settings, is interfering with his life.

Anxiety symptoms—including generalized nervousness and OCD-like obsessions and perseverations—are common psychotropic targets in FXS. Boys may be the FXS patients most often prescribed drugs for inattention and hyperactivity, but they are the least likely to receive antidepressants for anxiety symptoms.^1,2

Efficacy. More than 50% of female patients and men with FXS are prescribed SSRIs for anxiety (Table 2), and the reported response rate of 50% to 60%¹ is similar to that seen with SSRIs in autism and related disorders.¹⁸ In autism, a developmental approach is warranted, as SSRIs tend to be less effective and cause more side effects in children and adolescents than in adults.¹⁸

Adverse effects reported with SSRIs in FXS include behavioral activation, appetite changes, insomnia, and nausea.¹ In a study of fluoxetine for FXS symptoms, 10 of 35 patients (29%) had persistent side effects, most commonly weight loss and weight gain.¹⁹ One patient with pre-existing suicidal ideation worsened.

Watch for emergence or worsening of suicidal thoughts in all children and adolescents receiving antidepressants, whatever their target symptoms.

Mike is taking methylphenidate, 15 mg bid, for comorbid ADHD, and we add fluoxetine, 10 mg/d, for anxiety. This regimen is well-tolerated, so we increase fluoxetine to 20 mg/d at his 4-week follow-up appointment. After about 8 weeks, Mike’s parents report that his anxiety-associated symptoms are less severe.

Mike still appears nervous sometimes, but he uses markedly fewer perseverative phrases. This allows him to interact more meaningfully with peers and contributes to his social development.

Table 2

Target symptoms and treatment options for fragile X syndrome

Aggression and self-injury

Mike, now age 20 and participating daily in a vocational workshop, begins yelling profanities at coworkers. At his group home, he has been hitting staff at least twice a week when redirected.

He is no longer taking stimulants, having been weaned from methylphenidate several years ago, but he continues to take fluoxetine, 40 mg/d.

Fluoxetine¹⁹ and clonidine¹⁵ can decrease irritability in FXS, but atypical antipsychotics are most commonly used for aggression and SIB.^1,2 SGAs are prescribed to 10% to 20% of FXS patients who are taking medication^1,2—particularly to men—and have produced response rates of 60% to 100% when used for aggression and SIB.¹

Risperidone. No published reports have addressed using specific SGAs in FXS. In the PDD literature, most controlled data concerns risperidone.²⁰

The largest randomized, placebo-controlled trial enrolled 101 children ages 5 to 17 with autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior. Among the 49 children taking risperidone, 0.5 to 3.5 mg/d for 8 weeks, 34 (69%) were judged as treatment responders with significantly reduced irritable behavior, compared with 6 of 52 (12%) taking placebo.²¹ Risperidone therapy was associated with average weight gain of 2.7±2.9 kg, compared with 0.8±2.2 kg with placebo.

Besides weight gain, other significant side effects associated with risperidone include sedation and elevated serum prolactin. These effects often are more pronounced in children and adolescents than in adults with PDDs.²⁰

Other antipsychotics. Future use of SGAs in FXS will likely mirror the pattern seen in PDDs, where clinicians are moving towards weight-neutral antipsychotics such as ziprasidone and aripiprazole. In a preliminary report, aripiprazole reduced irritability in 5 youths with PDD.²² Our group is conducting a double-blind, placebo-controlled trial of aripiprazole in autism, targeting aggression, SIB, and irritability.

Discussion. SGAs are used most often in FXS to treat aggression and SIB, based on data from studies on treating similar symptoms in PDDs. Closely monitor patients for sedation, weight gain, and lipid, glucose, and prolactin elevations when using SGAs (Table 3). Be especially vigilant when children gain weight rapidly or show hyperprolactinemia signs while taking these drugs.

After being suspended from the vocational workshop, Mike is treated at a local mental health center for aggressive behaviors. He tolerates an initial dosage of aripiprazole,2.5 mg/d, which is titrated in 2.5-mg increments biweekly to 10 mg/d. At this dosage, he stops hitting staff members and his yelling of profanities is greatly reduced. Over several months, Mike returns to his vocational workshop and maintains residence at his group home.

Table 3

Medication side effects and recommended monitoring

Genetic-related treatments

Studies are needed to investigate the use of stimulants, SSRIs, and antipsychotics in patients with FXS unaccompanied by generalized anxiety disorder, OCD, ADHD, or PDDs. How FXS patients without those comorbidities will respond to drug treatment is unknown. Also, little also is known about possible side effects associated with combining drug treatments in individuals with FXS.

Future drug treatment in FXS will likely focus on agents that target the underlying neurochemical dysregulation associated with the FXS genotype. This approach might reduce interfering behaviors and alter the course of cognitive dysfunction—including mental retardation—associated with FXS.

Past attempts to correct FXS’ neurochemical abnormalities focused on using folic acid. The term “fragile X” describes how the X chromosome of individuals with FXS fractures in a folate-deprived medium. Many controlled trials of folic acid in FXS did not support earlier positive reports, however.⁴

Greater understanding of fragile X mental retardation protein (FMRP) function has led to the metabotropic glutamate receptor (mGluR) theory.⁷ It holds that FMRP underproduction allows exaggerated group 1 mGluR activity and leads to the FXS neurobehavioral phenotype. Researchers now are attempting to reverse the neurochemical impact of insufficient FMRP with two medication classes:

• selective group 1 mGluR receptor antagonists (mGluR5 antagonists, in particular). The mGluR5 receptor antagonist MPEP has shown the ability to rescue normal behaviors in animal models of FXS. MPEP and lithium have reversed behaviors associated with FXS and—at the microscopic level—rescued synaptic plasticity.^23,24 In the drosophila fly model of FXS, lithium reduced activity in the mGluR cascade, thus compensating for lack of FMRP.²³
  
• positive AMPA receptor modulators (ampakines) that promote activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.⁹ Excessive mGluR activity appears to impair AMPA receptors’ ability to promote cortical development, memory, and learning.⁷ Reduced AMPA receptors have been shown in the FXS mouse model,²⁵ and an ampakine is being investigated in a study of men with FXS and autism.¹
  

• FRAXA: The Fragile X Research Foundation. Founded by parents of children with fragile X syndrome to increase funding for research toward effective treatments. www.fraxa.org.
  
• The National Fragile X Foundation. Provides educational and emotional support for fragile X families and promotes public and professional awareness. www.fragilex.org.
  
• Hagerman RJ, Hagerman PJ, eds. Fragile X syndrome: diagnosis, treatment, and research, 3rd ed. Baltimore, MD: The Johns Hopkins University Press; 2002.
  

• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine • Dexedrine
  
• Fluoxetine • Prozac
  
• Guanfacine • Tenex
  
• Lithium • Eskalith, Lithobid
  
• Methylphenidate • Ritalin
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

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

Dr. Stigler receives grant/research support from Bristol-Myers Squibb Co. and Janssen Pharmaceutica.

Dr. Posey receives grant/research support from Forest Pharmaceuticals and Janssen Pharmaceutica and is a consultant to Forest Pharmaceuticals.

Dr. McDougle receives grant/research support from Forest Pharmaceuticals, Janssen Pharmaceutica, Bristol-Myers Squibb Co., and Eli Lilly and Co., and is a consultant to or speaker for Forest Pharmaceuticals, Janssen Pharmaceutica, Bristol-Myers Squibb Co., Eli Lilly and Co., and Pfizer Inc.