Cases That Test Your Skills

CASE: He bares it all

Police have arrested Mr. L, age 62, 3 times in 36 hours after spotting him walking naked in public. With the county jail jammed to capacity, police bring him each time to our hospital’s emergency room.

After his first arrest, Mr. L matter-of-factly tells us, “I want to walk naked and starve myself to death.” His self-harm exhortations amplify with each visit until—at the third presentation—he reports that he has not eaten for at least 2 days.

Mr. L had been living on the streets for nearly 1 month. Before that, he had been in jail for approximately 1 month after attacking a nursing home patient. He has been hospitalized twice in 5 months for severe depression and personality disorder and has engaged in numerous disruptive behavioral episodes and feeble suicide attempts. At this latest presentation, he appears disheveled and lacks judgment and insight into his condition.

We readmit Mr. L to the psychiatric unit to re-evaluate his treatment. He had been on citalopram, 60 mg/d, and aripiprazole, 10 mg/d, but he says he stopped taking the medications because they were not improving his mood.

The authors’ observations

We readmitted Mr. L with working diagnoses of:

• major depressive disorder with psychotic features, based on his suicide threats and complaints of depression
  
• personality disorder not otherwise specified, based on his behavioral episodes, apparent desire to be cared for (Table 1), and refusal to “get better” during 2 recent hospitalizations.
  

Table 1

A troubled life: Mr. L’s history

Period	Mr. L’s difficulties
Childhood	Has no friends in school; his mother—Mr. L’s sole source of emotional support—continues to wash his laundry, buy his food and clothes into his 20s
Adult life	Keeps ‘goofing off’ at work and has trouble staying employed; depends on wife to manage his life
2 years ago	Shows depressive symptoms (amotivation, lack of concentration, increased fatigue, decreased appetite) after shoulder injury Develops irrational fear that household appliances will malfunction Becomes hostile toward his wife of 34 years
5 months ago	Hospitalized after threatening to kill wife; has depressive symptoms and is disruptive during month-long hospitalization
4 months ago	Discharged from hospital to homeless shelter because estranged wife won’t allow him back home; is readmitted after shelter staff find him banging his head on an iron gate; again behaves disruptively
3 months ago	Discharged from second month-long hospitalization to nursing home
2 months ago	Attacks patient at nursing home; police arrest and incarcerate him on disorderly conduct charge
Past month	Released from jail after 1 month and spends weeks on the streets; lands in ER after police repeatedly catch him walking naked in public

HISTORY: His best friends

As a child, Mr. L had no friends. His father was physically present but emotionally distant, so he relied on his mother for emotional support. Throughout his teens and early adulthood, his mother continued to do his laundry, buy his food and clothes, and run his life. When he married in his early 20s, his wife assumed this role.

Mr. L avoided psychiatric care for most of his life but did not socialize outside the house, lacked ambition, and seemed content to depend on his wife. He worked primarily as a janitor or housekeeper but was constantly getting fired and drifted from job to job. His wife told us that when he was supposed to be working, he spent hours staring at the walls and watching TV.

Mr. L’s recent troubles began approximately 2 years ago, when he suffered a shoulder injury. He underwent physical therapy but refused needed surgery because he lacked money and health insurance.

As the shoulder pain intensified, Mr. L quit his job. While out of work, he stopped attending physical therapy sessions when his depressive symptoms began to offset the shoulder pain. He suffered loss of concentration and motivation, increased fatigue with hypersomnia, and decreased appetite. He lost 10 to 12 lb in 1 year.

Mr. L also started having trouble “focusing on reality” and developed obsessive fears of malfunctions around the house, such as the furnace blowing up, the stove catching fire, or the toilet backing up. At one point, he began urinating and defecating in his pants to avoid using the toilet. He began to feel hopeless and several times tried to suffocate himself by placing a plastic bag over his head.

He also grew irritable, angry, and aggressive—mostly toward his wife, who increasingly feared him. He started blaming her for “everything wrong in my life” and began contemplating stabbing her to death or striking her head with a hammer.

 

Five months ago, Mr. L was involuntarily hospitalized for depressive symptoms, suicidality, and continued homicidal thoughts toward his wife. The attending psychiatrist started olanzapine, 5 mg nightly, for psychotic features, and citalopram, 10 mg/d, for depression and anxiety, and ordered one-on-one observation to prevent additional suicide attempts. Mr. L’s shoulder pain had resolved by this time.

Three days later, Mr. L began refusing to eat. The psychiatrist then increased citalopram to 20 mg/d and olanzapine to 5 mg bid and asked a hospital internist to evaluate for malnutrition and a psychologist to gauge cognitive and intellectual function.

During the psychologist’s evaluation, Mr. L showed average global intellectual functioning but delays in visual-motor speed, visual working memory, and alertness to his environment. These findings, however, did not explain the patient’s lower functioning at home or in the hospital.

We ruled out organic causes for Mr. L’s cognitive deficits after receiving normal brain MRI, urinalysis, rapid plasma reagin titer, and thyroid-stimulating hormone test results. We also ruled out malnutrition because vitamin B12 and folate levels were normal but ordered a dietary consult to help Mr. L regain weight.

Staff and family registered Mr. L for Medicare and Medicaid benefits so that he could become more independent, but his behavior soon regressed. He complained that staff and family were ignoring him and started urinating outside the bathroom, eating and smearing his feces, and bothering other patients. Staff directed Mr. L’s wife to ignore his verbal abuse over the phone and encourage him to stay motivated for treatment.

Mr. L’s disruptive behavior stopped after the psychologist tried individual therapy with behavior modification. The psychologist helped him devise a cleanliness plan and encouraged him to express his anger verbally rather than acting out. When Mr. L smeared his feces, he was to scrub the area with soap and water, take a 5-minute cold shower, put on clean clothes, and write and read an apology to hospital staff.

DISCHARGE: Nowhere to go

One month after admission, Mr. L was free of suicidal and homicidal thoughts and other symptoms. Staff prepared him for discharge, but his wife was contemplating divorce and refused to allow him back home. He also declined community outpatient treatment because he wanted his life to return to “normal” and was unaware that he was harming himself and others.

With no other disposition options, we discharged Mr. L to a homeless shelter. Later that day, shelter staff brought him back to the ER after they found him banging his head against an iron gate. We readmitted him to the psychiatric unit, at which point he endorsed suicidal thinking.

READMISSION: ‘Cold’ case

During this second hospitalization, Mr. L was again eating his feces as well as coloring himself with green markers, writing obscenities on the wall, and tearing up other patients’ papers. He repeatedly took 15-minute cold showers and told staff as they urged him out of the shower that he wanted to die by inducing hypothermia. During these episodes, he often called his estranged wife and told her what he was doing.

After the treatment team had Mr. L civilly committed, the attending psychiatrist titrated citalopram to 60 mg/d, discontinued olanzapine, and added aripiprazole to target the patient’s underlying depressive symptoms. Aripiprazole was started at 5 mg nightly and eventually titrated to 10 mg nightly. On 3 occasions during the month-long hospitalization, Mr. L refused to take his medications because he felt he did not belong in the hospital.

The attending psychiatrist diagnosed “dependent, passive-aggressive behaviors” and noted that Mr. L was “not amenable” to psychiatric hospitalization. The treatment team and outpatient community mental health department decided the patient had a personality disorder and that continued hospitalization would prevent him from attaining autonomy.

We then discharged Mr. L to a nursing home. There, he demanded a transfer back to the hospital or to jail because he feared he could not afford nursing home care and believed he could receive more attention elsewhere. His request was rejected after our ER psychiatrist found him medically and mentally fit to stay at the nursing home.

About 1 month later, Mr. L tried to smother a female patient by holding a pillow over her face but stopped when she began to struggle. After he told the nurses what he had done, staff immediately called police, who arrested Mr. L and transferred him to the county jail.

Because police and nursing home staff viewed the incident as a cry for help rather than a cold-blooded attack, police charged Mr. L with disorderly conduct. One month later, police dropped the charge and released him to the streets.

 

The authors’ observations

Mr. L triggered hateful reactions among several treatment team members, many of whom felt vindicated by his arrest. Clinicians might react this way if they feel a patient is wasting their time, manipulating them, not recognizing their narcissistic need for the patient to change, or ignoring their treatment plans.¹

Acknowledging the staff’s—and your own—reaction to a difficult patient is critical. Not doing so can lead to treatment decisions based on emotions rather than evidence. In a busy clinical setting, it’s easy to lose sight of this.

The following strategies can help you manage hateful countertransference, cope with a patient’s offensive behaviors, and make appropriate decisions:

• Allow staff members to discuss their feelings. Encourage them to acknowledge and discuss their feelings during team meetings or daily treatment discussions. This helped members of our team recognize that their identification with Mr. L’s self-rejection fueled their desire to “reject” him by discharging him to police or the homeless shelter.
  
• Joke about the patient’s behavior when appropriate. Humor is a mature and potentially healing defense mechanism. When not treating Mr. L, for example, we joked among ourselves about publishing a case report titled, “The case of the poop-eater.” Never joke about the patient in the therapeutic milieu, where it can be disruptive.
  
• See the behavior as a defense mechanism. Viewing patients’ reactions as defense mechanisms—rather than effects of a psychiatric disorder—can help you better understand the patient’s underlying pathophysiology.
  

READMISSION: More bad behavior

After his 3 arrests for public nudity, we readmit Mr. L, restart citalopram at 20 mg/d, and titrate it back to 60 mg/d to target his depression. We also switch back to olanzapine, 10 mg nightly, because the patient has seen little clinical benefit from aripiprazole and feels that olanzapine had improved his sleep.

In the psychiatric ward, Mr. L is once again disturbing patients, smearing and eating feces, and making half-hearted suicide attempts. Upset that staff is “ignoring” him, he enters other patients’ rooms without invitation and urinates in places other than the bathroom.

The authors’ observations

After 3 hospital admissions, Mr. L’s diagnosis remained unclear (Table 2). At his first admission, his symptoms suggested major depression with psychotic features. With his subsequent behaviors in the inpatient psychiatric unit—including primitive suicide attempts and smearing and eating feces—Mr. L showed a strong desire to be cared for. This and his past dependence on his wife and mother suggested a severe dependent personality disorder.

At his first discharge, Mr. L was diagnosed with a personality disorder with significant passive-aggressive traits. His lifelong dysphoria and lack of ambition also suggested dysthymia.

With discharge from this latest hospitalization pending, we searched for options. We considered Mr. L’s ongoing suicidality, persistent acting out, and aggression. Treatment team members discussed his use of “primitive defenses”² stemming from his limited coping skills in the face of severe depression.

Table 2

Mr. L’s differential diagnosis

Possible diagnosis	Mr. L’s symptoms
Major depression	Diminished motivation, concentration, and appetite Increased fatigue, hypersomnia Suicidal thinking
Personality disorder	Primitive, dependent behaviors Abnormal dependence on wife, mother
Depression with psychotic features	Depressive symptoms with obsessive suicidal/homicidal thoughts, fears of household malfunctions

TREATMENT: A different course

One week after admission, Mr. L’s inpatient psychiatrist recommends electroconvulsive therapy (ECT) to target the patient’s presumed severe depressive episodes and disruptive behaviors. The psychiatrist is experienced in performing ECT, which in clinical trials³ has shown efficacy in treatment-refractory major depression.

After giving informed consent, Mr. L receives 8 bilateral ECT treatments in 3 weeks. Also, the hospital psychologist performs behavioral modification similar to the previous cleanliness plan and again encourages Mr. L to express his anger and anxiety verbally.

By the second week of ECT, Mr. L’s disruptive behaviors have ceased. By the end of week 3, his mood and motivation have improved to the point where he shows interest in becoming independent. He says he wants to show his estranged wife he can care for himself and eventually reunite with her.

As Mr. L continues to improve, we discharge him to outpatient community mental health services and continue citalopram, 60 mg/d, and olanzapine, 5 mg nightly.

Nearly 2 years later, Mr. L is living independently. He has been regularly seeing his psychiatrist at the community mental health center and is maintained on citalopram and olanzapine. He continues trying to make amends with his wife but is still out of work and receives Social Security disability benefits.

The authors’ observations

Mr. L was fortunate that his inpatient psychiatrist could re-evaluate the diagnosis after identifying the staff’s significantly hateful countertransference. This allowed staff to offer ECT, which—despite its documented efficacy for major depression—is not widely available in the United States.

 

If no ECT providers were available, we would have considered medication change and long-term treatment in a state mental hospital until Mr. L showed he could care for himself.

Related resources

• Nagera H. Countertransference (PowerPoint presentation). Tampa, FL: The Carter Jenkins Center; 2003. www.thecjc.org/ppoint/ppoint/ct.ppt.
  
• MayoClinic.com video: Electroconvulsive therapy (ECT): One woman’s journey. Click on “Video” at top, then scroll to title.
  

Drug brand names

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Citalopram • Celexa
  

Disclosure

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

CASE: He bares it all

Police have arrested Mr. L, age 62, 3 times in 36 hours after spotting him walking naked in public. With the county jail jammed to capacity, police bring him each time to our hospital’s emergency room.

After his first arrest, Mr. L matter-of-factly tells us, “I want to walk naked and starve myself to death.” His self-harm exhortations amplify with each visit until—at the third presentation—he reports that he has not eaten for at least 2 days.

Mr. L had been living on the streets for nearly 1 month. Before that, he had been in jail for approximately 1 month after attacking a nursing home patient. He has been hospitalized twice in 5 months for severe depression and personality disorder and has engaged in numerous disruptive behavioral episodes and feeble suicide attempts. At this latest presentation, he appears disheveled and lacks judgment and insight into his condition.

We readmit Mr. L to the psychiatric unit to re-evaluate his treatment. He had been on citalopram, 60 mg/d, and aripiprazole, 10 mg/d, but he says he stopped taking the medications because they were not improving his mood.

The authors’ observations

We readmitted Mr. L with working diagnoses of:

• major depressive disorder with psychotic features, based on his suicide threats and complaints of depression
  
• personality disorder not otherwise specified, based on his behavioral episodes, apparent desire to be cared for (Table 1), and refusal to “get better” during 2 recent hospitalizations.
  

Table 1

A troubled life: Mr. L’s history

Period	Mr. L’s difficulties
Childhood	Has no friends in school; his mother—Mr. L’s sole source of emotional support—continues to wash his laundry, buy his food and clothes into his 20s
Adult life	Keeps ‘goofing off’ at work and has trouble staying employed; depends on wife to manage his life
2 years ago	Shows depressive symptoms (amotivation, lack of concentration, increased fatigue, decreased appetite) after shoulder injury Develops irrational fear that household appliances will malfunction Becomes hostile toward his wife of 34 years
5 months ago	Hospitalized after threatening to kill wife; has depressive symptoms and is disruptive during month-long hospitalization
4 months ago	Discharged from hospital to homeless shelter because estranged wife won’t allow him back home; is readmitted after shelter staff find him banging his head on an iron gate; again behaves disruptively
3 months ago	Discharged from second month-long hospitalization to nursing home
2 months ago	Attacks patient at nursing home; police arrest and incarcerate him on disorderly conduct charge
Past month	Released from jail after 1 month and spends weeks on the streets; lands in ER after police repeatedly catch him walking naked in public

HISTORY: His best friends

As a child, Mr. L had no friends. His father was physically present but emotionally distant, so he relied on his mother for emotional support. Throughout his teens and early adulthood, his mother continued to do his laundry, buy his food and clothes, and run his life. When he married in his early 20s, his wife assumed this role.

Mr. L avoided psychiatric care for most of his life but did not socialize outside the house, lacked ambition, and seemed content to depend on his wife. He worked primarily as a janitor or housekeeper but was constantly getting fired and drifted from job to job. His wife told us that when he was supposed to be working, he spent hours staring at the walls and watching TV.

Mr. L’s recent troubles began approximately 2 years ago, when he suffered a shoulder injury. He underwent physical therapy but refused needed surgery because he lacked money and health insurance.

As the shoulder pain intensified, Mr. L quit his job. While out of work, he stopped attending physical therapy sessions when his depressive symptoms began to offset the shoulder pain. He suffered loss of concentration and motivation, increased fatigue with hypersomnia, and decreased appetite. He lost 10 to 12 lb in 1 year.

Mr. L also started having trouble “focusing on reality” and developed obsessive fears of malfunctions around the house, such as the furnace blowing up, the stove catching fire, or the toilet backing up. At one point, he began urinating and defecating in his pants to avoid using the toilet. He began to feel hopeless and several times tried to suffocate himself by placing a plastic bag over his head.

He also grew irritable, angry, and aggressive—mostly toward his wife, who increasingly feared him. He started blaming her for “everything wrong in my life” and began contemplating stabbing her to death or striking her head with a hammer.

 

Five months ago, Mr. L was involuntarily hospitalized for depressive symptoms, suicidality, and continued homicidal thoughts toward his wife. The attending psychiatrist started olanzapine, 5 mg nightly, for psychotic features, and citalopram, 10 mg/d, for depression and anxiety, and ordered one-on-one observation to prevent additional suicide attempts. Mr. L’s shoulder pain had resolved by this time.

Three days later, Mr. L began refusing to eat. The psychiatrist then increased citalopram to 20 mg/d and olanzapine to 5 mg bid and asked a hospital internist to evaluate for malnutrition and a psychologist to gauge cognitive and intellectual function.

During the psychologist’s evaluation, Mr. L showed average global intellectual functioning but delays in visual-motor speed, visual working memory, and alertness to his environment. These findings, however, did not explain the patient’s lower functioning at home or in the hospital.

We ruled out organic causes for Mr. L’s cognitive deficits after receiving normal brain MRI, urinalysis, rapid plasma reagin titer, and thyroid-stimulating hormone test results. We also ruled out malnutrition because vitamin B12 and folate levels were normal but ordered a dietary consult to help Mr. L regain weight.

Staff and family registered Mr. L for Medicare and Medicaid benefits so that he could become more independent, but his behavior soon regressed. He complained that staff and family were ignoring him and started urinating outside the bathroom, eating and smearing his feces, and bothering other patients. Staff directed Mr. L’s wife to ignore his verbal abuse over the phone and encourage him to stay motivated for treatment.

Mr. L’s disruptive behavior stopped after the psychologist tried individual therapy with behavior modification. The psychologist helped him devise a cleanliness plan and encouraged him to express his anger verbally rather than acting out. When Mr. L smeared his feces, he was to scrub the area with soap and water, take a 5-minute cold shower, put on clean clothes, and write and read an apology to hospital staff.

DISCHARGE: Nowhere to go

One month after admission, Mr. L was free of suicidal and homicidal thoughts and other symptoms. Staff prepared him for discharge, but his wife was contemplating divorce and refused to allow him back home. He also declined community outpatient treatment because he wanted his life to return to “normal” and was unaware that he was harming himself and others.

With no other disposition options, we discharged Mr. L to a homeless shelter. Later that day, shelter staff brought him back to the ER after they found him banging his head against an iron gate. We readmitted him to the psychiatric unit, at which point he endorsed suicidal thinking.

READMISSION: ‘Cold’ case

During this second hospitalization, Mr. L was again eating his feces as well as coloring himself with green markers, writing obscenities on the wall, and tearing up other patients’ papers. He repeatedly took 15-minute cold showers and told staff as they urged him out of the shower that he wanted to die by inducing hypothermia. During these episodes, he often called his estranged wife and told her what he was doing.

After the treatment team had Mr. L civilly committed, the attending psychiatrist titrated citalopram to 60 mg/d, discontinued olanzapine, and added aripiprazole to target the patient’s underlying depressive symptoms. Aripiprazole was started at 5 mg nightly and eventually titrated to 10 mg nightly. On 3 occasions during the month-long hospitalization, Mr. L refused to take his medications because he felt he did not belong in the hospital.

The attending psychiatrist diagnosed “dependent, passive-aggressive behaviors” and noted that Mr. L was “not amenable” to psychiatric hospitalization. The treatment team and outpatient community mental health department decided the patient had a personality disorder and that continued hospitalization would prevent him from attaining autonomy.

We then discharged Mr. L to a nursing home. There, he demanded a transfer back to the hospital or to jail because he feared he could not afford nursing home care and believed he could receive more attention elsewhere. His request was rejected after our ER psychiatrist found him medically and mentally fit to stay at the nursing home.

About 1 month later, Mr. L tried to smother a female patient by holding a pillow over her face but stopped when she began to struggle. After he told the nurses what he had done, staff immediately called police, who arrested Mr. L and transferred him to the county jail.

Because police and nursing home staff viewed the incident as a cry for help rather than a cold-blooded attack, police charged Mr. L with disorderly conduct. One month later, police dropped the charge and released him to the streets.

 

The authors’ observations

Mr. L triggered hateful reactions among several treatment team members, many of whom felt vindicated by his arrest. Clinicians might react this way if they feel a patient is wasting their time, manipulating them, not recognizing their narcissistic need for the patient to change, or ignoring their treatment plans.¹

Acknowledging the staff’s—and your own—reaction to a difficult patient is critical. Not doing so can lead to treatment decisions based on emotions rather than evidence. In a busy clinical setting, it’s easy to lose sight of this.

The following strategies can help you manage hateful countertransference, cope with a patient’s offensive behaviors, and make appropriate decisions:

• Allow staff members to discuss their feelings. Encourage them to acknowledge and discuss their feelings during team meetings or daily treatment discussions. This helped members of our team recognize that their identification with Mr. L’s self-rejection fueled their desire to “reject” him by discharging him to police or the homeless shelter.
  
• Joke about the patient’s behavior when appropriate. Humor is a mature and potentially healing defense mechanism. When not treating Mr. L, for example, we joked among ourselves about publishing a case report titled, “The case of the poop-eater.” Never joke about the patient in the therapeutic milieu, where it can be disruptive.
  
• See the behavior as a defense mechanism. Viewing patients’ reactions as defense mechanisms—rather than effects of a psychiatric disorder—can help you better understand the patient’s underlying pathophysiology.
  

READMISSION: More bad behavior

After his 3 arrests for public nudity, we readmit Mr. L, restart citalopram at 20 mg/d, and titrate it back to 60 mg/d to target his depression. We also switch back to olanzapine, 10 mg nightly, because the patient has seen little clinical benefit from aripiprazole and feels that olanzapine had improved his sleep.

In the psychiatric ward, Mr. L is once again disturbing patients, smearing and eating feces, and making half-hearted suicide attempts. Upset that staff is “ignoring” him, he enters other patients’ rooms without invitation and urinates in places other than the bathroom.

The authors’ observations

After 3 hospital admissions, Mr. L’s diagnosis remained unclear (Table 2). At his first admission, his symptoms suggested major depression with psychotic features. With his subsequent behaviors in the inpatient psychiatric unit—including primitive suicide attempts and smearing and eating feces—Mr. L showed a strong desire to be cared for. This and his past dependence on his wife and mother suggested a severe dependent personality disorder.

At his first discharge, Mr. L was diagnosed with a personality disorder with significant passive-aggressive traits. His lifelong dysphoria and lack of ambition also suggested dysthymia.

With discharge from this latest hospitalization pending, we searched for options. We considered Mr. L’s ongoing suicidality, persistent acting out, and aggression. Treatment team members discussed his use of “primitive defenses”² stemming from his limited coping skills in the face of severe depression.

Table 2

Mr. L’s differential diagnosis

Possible diagnosis	Mr. L’s symptoms
Major depression	Diminished motivation, concentration, and appetite Increased fatigue, hypersomnia Suicidal thinking
Personality disorder	Primitive, dependent behaviors Abnormal dependence on wife, mother
Depression with psychotic features	Depressive symptoms with obsessive suicidal/homicidal thoughts, fears of household malfunctions

TREATMENT: A different course

One week after admission, Mr. L’s inpatient psychiatrist recommends electroconvulsive therapy (ECT) to target the patient’s presumed severe depressive episodes and disruptive behaviors. The psychiatrist is experienced in performing ECT, which in clinical trials³ has shown efficacy in treatment-refractory major depression.

After giving informed consent, Mr. L receives 8 bilateral ECT treatments in 3 weeks. Also, the hospital psychologist performs behavioral modification similar to the previous cleanliness plan and again encourages Mr. L to express his anger and anxiety verbally.

By the second week of ECT, Mr. L’s disruptive behaviors have ceased. By the end of week 3, his mood and motivation have improved to the point where he shows interest in becoming independent. He says he wants to show his estranged wife he can care for himself and eventually reunite with her.

As Mr. L continues to improve, we discharge him to outpatient community mental health services and continue citalopram, 60 mg/d, and olanzapine, 5 mg nightly.

Nearly 2 years later, Mr. L is living independently. He has been regularly seeing his psychiatrist at the community mental health center and is maintained on citalopram and olanzapine. He continues trying to make amends with his wife but is still out of work and receives Social Security disability benefits.

The authors’ observations

Mr. L was fortunate that his inpatient psychiatrist could re-evaluate the diagnosis after identifying the staff’s significantly hateful countertransference. This allowed staff to offer ECT, which—despite its documented efficacy for major depression—is not widely available in the United States.

 

If no ECT providers were available, we would have considered medication change and long-term treatment in a state mental hospital until Mr. L showed he could care for himself.

Related resources

• Nagera H. Countertransference (PowerPoint presentation). Tampa, FL: The Carter Jenkins Center; 2003. www.thecjc.org/ppoint/ppoint/ct.ppt.
  
• MayoClinic.com video: Electroconvulsive therapy (ECT): One woman’s journey. Click on “Video” at top, then scroll to title.
  

Drug brand names

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Citalopram • Celexa
  

Disclosure

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

CASE: He bares it all

Police have arrested Mr. L, age 62, 3 times in 36 hours after spotting him walking naked in public. With the county jail jammed to capacity, police bring him each time to our hospital’s emergency room.

After his first arrest, Mr. L matter-of-factly tells us, “I want to walk naked and starve myself to death.” His self-harm exhortations amplify with each visit until—at the third presentation—he reports that he has not eaten for at least 2 days.

Mr. L had been living on the streets for nearly 1 month. Before that, he had been in jail for approximately 1 month after attacking a nursing home patient. He has been hospitalized twice in 5 months for severe depression and personality disorder and has engaged in numerous disruptive behavioral episodes and feeble suicide attempts. At this latest presentation, he appears disheveled and lacks judgment and insight into his condition.

We readmit Mr. L to the psychiatric unit to re-evaluate his treatment. He had been on citalopram, 60 mg/d, and aripiprazole, 10 mg/d, but he says he stopped taking the medications because they were not improving his mood.

The authors’ observations

We readmitted Mr. L with working diagnoses of:

• major depressive disorder with psychotic features, based on his suicide threats and complaints of depression
  
• personality disorder not otherwise specified, based on his behavioral episodes, apparent desire to be cared for (Table 1), and refusal to “get better” during 2 recent hospitalizations.
  

Table 1

A troubled life: Mr. L’s history

Period	Mr. L’s difficulties
Childhood	Has no friends in school; his mother—Mr. L’s sole source of emotional support—continues to wash his laundry, buy his food and clothes into his 20s
Adult life	Keeps ‘goofing off’ at work and has trouble staying employed; depends on wife to manage his life
2 years ago	Shows depressive symptoms (amotivation, lack of concentration, increased fatigue, decreased appetite) after shoulder injury Develops irrational fear that household appliances will malfunction Becomes hostile toward his wife of 34 years
5 months ago	Hospitalized after threatening to kill wife; has depressive symptoms and is disruptive during month-long hospitalization
4 months ago	Discharged from hospital to homeless shelter because estranged wife won’t allow him back home; is readmitted after shelter staff find him banging his head on an iron gate; again behaves disruptively
3 months ago	Discharged from second month-long hospitalization to nursing home
2 months ago	Attacks patient at nursing home; police arrest and incarcerate him on disorderly conduct charge
Past month	Released from jail after 1 month and spends weeks on the streets; lands in ER after police repeatedly catch him walking naked in public

HISTORY: His best friends

As a child, Mr. L had no friends. His father was physically present but emotionally distant, so he relied on his mother for emotional support. Throughout his teens and early adulthood, his mother continued to do his laundry, buy his food and clothes, and run his life. When he married in his early 20s, his wife assumed this role.

Mr. L avoided psychiatric care for most of his life but did not socialize outside the house, lacked ambition, and seemed content to depend on his wife. He worked primarily as a janitor or housekeeper but was constantly getting fired and drifted from job to job. His wife told us that when he was supposed to be working, he spent hours staring at the walls and watching TV.

Mr. L’s recent troubles began approximately 2 years ago, when he suffered a shoulder injury. He underwent physical therapy but refused needed surgery because he lacked money and health insurance.

As the shoulder pain intensified, Mr. L quit his job. While out of work, he stopped attending physical therapy sessions when his depressive symptoms began to offset the shoulder pain. He suffered loss of concentration and motivation, increased fatigue with hypersomnia, and decreased appetite. He lost 10 to 12 lb in 1 year.

Mr. L also started having trouble “focusing on reality” and developed obsessive fears of malfunctions around the house, such as the furnace blowing up, the stove catching fire, or the toilet backing up. At one point, he began urinating and defecating in his pants to avoid using the toilet. He began to feel hopeless and several times tried to suffocate himself by placing a plastic bag over his head.

He also grew irritable, angry, and aggressive—mostly toward his wife, who increasingly feared him. He started blaming her for “everything wrong in my life” and began contemplating stabbing her to death or striking her head with a hammer.

 

Five months ago, Mr. L was involuntarily hospitalized for depressive symptoms, suicidality, and continued homicidal thoughts toward his wife. The attending psychiatrist started olanzapine, 5 mg nightly, for psychotic features, and citalopram, 10 mg/d, for depression and anxiety, and ordered one-on-one observation to prevent additional suicide attempts. Mr. L’s shoulder pain had resolved by this time.

Three days later, Mr. L began refusing to eat. The psychiatrist then increased citalopram to 20 mg/d and olanzapine to 5 mg bid and asked a hospital internist to evaluate for malnutrition and a psychologist to gauge cognitive and intellectual function.

During the psychologist’s evaluation, Mr. L showed average global intellectual functioning but delays in visual-motor speed, visual working memory, and alertness to his environment. These findings, however, did not explain the patient’s lower functioning at home or in the hospital.

We ruled out organic causes for Mr. L’s cognitive deficits after receiving normal brain MRI, urinalysis, rapid plasma reagin titer, and thyroid-stimulating hormone test results. We also ruled out malnutrition because vitamin B12 and folate levels were normal but ordered a dietary consult to help Mr. L regain weight.

Staff and family registered Mr. L for Medicare and Medicaid benefits so that he could become more independent, but his behavior soon regressed. He complained that staff and family were ignoring him and started urinating outside the bathroom, eating and smearing his feces, and bothering other patients. Staff directed Mr. L’s wife to ignore his verbal abuse over the phone and encourage him to stay motivated for treatment.

Mr. L’s disruptive behavior stopped after the psychologist tried individual therapy with behavior modification. The psychologist helped him devise a cleanliness plan and encouraged him to express his anger verbally rather than acting out. When Mr. L smeared his feces, he was to scrub the area with soap and water, take a 5-minute cold shower, put on clean clothes, and write and read an apology to hospital staff.

DISCHARGE: Nowhere to go

One month after admission, Mr. L was free of suicidal and homicidal thoughts and other symptoms. Staff prepared him for discharge, but his wife was contemplating divorce and refused to allow him back home. He also declined community outpatient treatment because he wanted his life to return to “normal” and was unaware that he was harming himself and others.

With no other disposition options, we discharged Mr. L to a homeless shelter. Later that day, shelter staff brought him back to the ER after they found him banging his head against an iron gate. We readmitted him to the psychiatric unit, at which point he endorsed suicidal thinking.

READMISSION: ‘Cold’ case

During this second hospitalization, Mr. L was again eating his feces as well as coloring himself with green markers, writing obscenities on the wall, and tearing up other patients’ papers. He repeatedly took 15-minute cold showers and told staff as they urged him out of the shower that he wanted to die by inducing hypothermia. During these episodes, he often called his estranged wife and told her what he was doing.

After the treatment team had Mr. L civilly committed, the attending psychiatrist titrated citalopram to 60 mg/d, discontinued olanzapine, and added aripiprazole to target the patient’s underlying depressive symptoms. Aripiprazole was started at 5 mg nightly and eventually titrated to 10 mg nightly. On 3 occasions during the month-long hospitalization, Mr. L refused to take his medications because he felt he did not belong in the hospital.

The attending psychiatrist diagnosed “dependent, passive-aggressive behaviors” and noted that Mr. L was “not amenable” to psychiatric hospitalization. The treatment team and outpatient community mental health department decided the patient had a personality disorder and that continued hospitalization would prevent him from attaining autonomy.

We then discharged Mr. L to a nursing home. There, he demanded a transfer back to the hospital or to jail because he feared he could not afford nursing home care and believed he could receive more attention elsewhere. His request was rejected after our ER psychiatrist found him medically and mentally fit to stay at the nursing home.

About 1 month later, Mr. L tried to smother a female patient by holding a pillow over her face but stopped when she began to struggle. After he told the nurses what he had done, staff immediately called police, who arrested Mr. L and transferred him to the county jail.

Because police and nursing home staff viewed the incident as a cry for help rather than a cold-blooded attack, police charged Mr. L with disorderly conduct. One month later, police dropped the charge and released him to the streets.

 

The authors’ observations

Mr. L triggered hateful reactions among several treatment team members, many of whom felt vindicated by his arrest. Clinicians might react this way if they feel a patient is wasting their time, manipulating them, not recognizing their narcissistic need for the patient to change, or ignoring their treatment plans.¹

Acknowledging the staff’s—and your own—reaction to a difficult patient is critical. Not doing so can lead to treatment decisions based on emotions rather than evidence. In a busy clinical setting, it’s easy to lose sight of this.

The following strategies can help you manage hateful countertransference, cope with a patient’s offensive behaviors, and make appropriate decisions:

• Allow staff members to discuss their feelings. Encourage them to acknowledge and discuss their feelings during team meetings or daily treatment discussions. This helped members of our team recognize that their identification with Mr. L’s self-rejection fueled their desire to “reject” him by discharging him to police or the homeless shelter.
  
• Joke about the patient’s behavior when appropriate. Humor is a mature and potentially healing defense mechanism. When not treating Mr. L, for example, we joked among ourselves about publishing a case report titled, “The case of the poop-eater.” Never joke about the patient in the therapeutic milieu, where it can be disruptive.
  
• See the behavior as a defense mechanism. Viewing patients’ reactions as defense mechanisms—rather than effects of a psychiatric disorder—can help you better understand the patient’s underlying pathophysiology.
  

READMISSION: More bad behavior

After his 3 arrests for public nudity, we readmit Mr. L, restart citalopram at 20 mg/d, and titrate it back to 60 mg/d to target his depression. We also switch back to olanzapine, 10 mg nightly, because the patient has seen little clinical benefit from aripiprazole and feels that olanzapine had improved his sleep.

In the psychiatric ward, Mr. L is once again disturbing patients, smearing and eating feces, and making half-hearted suicide attempts. Upset that staff is “ignoring” him, he enters other patients’ rooms without invitation and urinates in places other than the bathroom.

The authors’ observations

After 3 hospital admissions, Mr. L’s diagnosis remained unclear (Table 2). At his first admission, his symptoms suggested major depression with psychotic features. With his subsequent behaviors in the inpatient psychiatric unit—including primitive suicide attempts and smearing and eating feces—Mr. L showed a strong desire to be cared for. This and his past dependence on his wife and mother suggested a severe dependent personality disorder.

At his first discharge, Mr. L was diagnosed with a personality disorder with significant passive-aggressive traits. His lifelong dysphoria and lack of ambition also suggested dysthymia.

With discharge from this latest hospitalization pending, we searched for options. We considered Mr. L’s ongoing suicidality, persistent acting out, and aggression. Treatment team members discussed his use of “primitive defenses”² stemming from his limited coping skills in the face of severe depression.

Table 2

Mr. L’s differential diagnosis

Possible diagnosis	Mr. L’s symptoms
Major depression	Diminished motivation, concentration, and appetite Increased fatigue, hypersomnia Suicidal thinking
Personality disorder	Primitive, dependent behaviors Abnormal dependence on wife, mother
Depression with psychotic features	Depressive symptoms with obsessive suicidal/homicidal thoughts, fears of household malfunctions

TREATMENT: A different course

One week after admission, Mr. L’s inpatient psychiatrist recommends electroconvulsive therapy (ECT) to target the patient’s presumed severe depressive episodes and disruptive behaviors. The psychiatrist is experienced in performing ECT, which in clinical trials³ has shown efficacy in treatment-refractory major depression.

After giving informed consent, Mr. L receives 8 bilateral ECT treatments in 3 weeks. Also, the hospital psychologist performs behavioral modification similar to the previous cleanliness plan and again encourages Mr. L to express his anger and anxiety verbally.

By the second week of ECT, Mr. L’s disruptive behaviors have ceased. By the end of week 3, his mood and motivation have improved to the point where he shows interest in becoming independent. He says he wants to show his estranged wife he can care for himself and eventually reunite with her.

As Mr. L continues to improve, we discharge him to outpatient community mental health services and continue citalopram, 60 mg/d, and olanzapine, 5 mg nightly.

Nearly 2 years later, Mr. L is living independently. He has been regularly seeing his psychiatrist at the community mental health center and is maintained on citalopram and olanzapine. He continues trying to make amends with his wife but is still out of work and receives Social Security disability benefits.

The authors’ observations

Mr. L was fortunate that his inpatient psychiatrist could re-evaluate the diagnosis after identifying the staff’s significantly hateful countertransference. This allowed staff to offer ECT, which—despite its documented efficacy for major depression—is not widely available in the United States.

 

If no ECT providers were available, we would have considered medication change and long-term treatment in a state mental hospital until Mr. L showed he could care for himself.

Related resources

• Nagera H. Countertransference (PowerPoint presentation). Tampa, FL: The Carter Jenkins Center; 2003. www.thecjc.org/ppoint/ppoint/ct.ppt.
  
• MayoClinic.com video: Electroconvulsive therapy (ECT): One woman’s journey. Click on “Video” at top, then scroll to title.
  

Drug brand names

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Citalopram • Celexa
  

Disclosure

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

CASE: A ‘purification’

Mr. B, age 61, is in the ICU after shooting himself in the abdomen. The trauma team asks our psychiatry consultation/liaison service to determine if he needs special observation to prevent further self-harm.

Two days ago, Mr. B stood in the parking lot of a nearby hospital, aimed his rifle toward the left upper part of his abdomen, and fired. Bleeding profusely, he dragged himself to the hospital’s emergency room. ER staff stabilized him hemodynamically, then transferred him to our hospital’s regional trauma center, where surgeons performed an emergency laparotomy and found 2 sigmoid colon perforations, with feces floating outside the bowel.

After a partial colectomy and colostomy, Mr. B received broad-spectrum antibiotics, narcotic pain medication, and bowel rest in the ICU. When the trauma team called us, the patient’s condition was stable and he had awakened enough to communicate, although he still needed frequent monitoring.

We visit Mr. B in the ICU and ask him why he shot himself. He denies he was attempting suicide but adds that for months he has been feeling depressed, stressed, and guilty about “all the bad things I’ve done in my life.” Shooting himself helped him forget these negative thoughts.

A devout Roman Catholic, Mr. B has been researching flagellation and other forms of physical penance and considers the shooting a purification. He says he shot himself in the abdomen 2 previous times and felt better for months or years after each shooting.

Four years ago, Mr. B donated his left kidney to an unknown recipient. He does not equate the kidney donation with the shootings but says he felt happy while recuperating. He was later disappointed, however, because the procedure did not help him attract the “attention” he had hoped for.

Mr. B says he had been considering the latest shooting for at least 8 months and had carefully planned it. After studying anatomy textbooks, he figured he could fire into the left upper portion of his abdomen without striking a vital organ.

For several evenings, Mr. B aimed his rifle toward his abdomen but could not bring himself to pull the trigger. On the night of the shooting, he said, he “accidentally” fired at a more damaging angle than he had planned.

Cognitive examination results are mostly normal, although Mr. B has trouble interpreting similarities and proverbs. He appears pale but well-nourished, well-groomed, and serene. He speaks softly, often closing his eyes or staring into the distance. He says he feels “relieved” and “happy” after the shooting but did not anticipate such a severe injury. He denies suicidal thoughts and—because of his current euphoric mood—he hopes he never “needs” to shoot himself again.

The authors’ observations

We first considered delusional disorder and major depressive disorder with psychotic features. Mr. B’s belief that shooting himself would solve his problems seemed delusional, although he did not appear psychotic otherwise. Confusingly, Mr. B’s pre-admission symptoms seemed to suggest major depressive disorder, but he was happy in the ICU.

We explored other diagnoses, such as an odd form of OCD and a personality disorder (especially cluster A, given his strange beliefs), though at this point we had too little information for either diagnosis.

We also wondered if Mr. B’s behavior was normal given his strong belief in Catholic penance. Although some sects of the Catholic Church practice self-flagellation and other forms of self-punishment,^1-3 we found no evidence that the church condones or encourages self-shooting. Moreover, Mr. B admitted during questioning that a Catholic clergy member told him shooting oneself is not an appropriate penance.

The authors’ observations

Mr. B was recovering from major abdominal surgery, was taking nothing orally, and claimed to feel fine psychologically. Because he was not grossly psychotic and did not endorse anxiety or depression, we decided against medication but recommended a chaplain consult and planned to visit Mr. B daily to gather more history.

We considered Mr. B a low suicide risk—especially while hospitalized—after he said his “need” to shoot himself had dissipated. He also endorsed no suicidal thoughts or other depressive symptoms, and the nursing staff viewed him as pleasant and compliant. We noted this evidence in the chart and continued to reassess him daily.

HISTORY: Dreams, nightmares

Over the next week, Mr. B shares his life story. He says his parents divorced when he was age 5, and around that time he spent approximately 2 weeks in the hospital after being hit by a truck. He considers those 2 weeks a bright spot in an otherwise turbulent childhood because his parents did not fight and he was showered with gifts and attention.

 

Soon after, Mr. B lived with his mother. When he was 9, he heard his divorced parents arguing during a family gathering and prayed for his own death.

Throughout his childhood, Mr. B dreamed of becoming a priest and a war hero. In his early teens, he attended a church youth program where he and other youths were taught that masturbation is a mortal sin. Through high school, Mr. B’s inability to stop masturbating shook his faith and discouraged him from pursuing the priesthood.

In high school, Mr. B did not use alcohol or drugs and excelled academically but had few friends. After graduating, he enlisted in the U.S. Army and hoped to serve in Vietnam, but basic training became too stressful. The relentless harangues from drill instructors reminded him of his parents’ frequent shouting matches during his childhood.

Approximately 2 weeks into basic training, Mr. B shot himself in the abdomen and injured his liver. He underwent laparotomy and cholecystectomy and was discharged from the military. His anxiety dissipated as he recovered, though he later regretted not serving in Vietnam.

Mr. B married at age 44 and was divorced 13 years later. Throughout the marriage, he says, he verbally abused his wife and was emotionally unsupportive. After the divorce, he felt remorse over having mistreated her. His guilt disappeared after he donated his left kidney to an unknown recipient, but the guilt soon returned and drove him to shoot himself a second time in 2005.

Mr. B worked as a special education teacher for 20 years before retiring 4 years ago and has since been pursuing a similar position because he misses going to work. His inability to find a permanent job has led to anxiety, insomnia, increased guilt, and decreased appetite. He says these feelings fueled his desire to shoot himself a third time.

Since his divorce, Mr. B has lived alone and has no family or friends nearby. He feels isolated and is hurt that his family has not acknowledged the cards and notes he sent to them but adds that he did not include his return address on the mailings.

FOLLOW-UP: No relief

After 1 week in the ICU, Mr. B is transferred to the surgical ward. His condition is fair and he continues to receive IV antibiotics; analgesics as needed; omeprazole, 20 mg/d, to prevent a stress ulcer; bowel care medications; and ostomy care and education. We continue to visit him in the surgical ward almost daily. He seems to enjoy our visits, during which he openly discusses his past.

Eleven days after admission, Mr. B says shooting himself has not relieved his negative feelings, and his impending discharge makes him feel anxious with some suicidal thoughts. The surgical team delays discharge after Mr. B develops ileus with nausea and vomiting. The trauma team’s attending physician prescribes an antiemetic, and ileus resolves after 4 days. Mr. B then is discharged in stable condition after he denies intention to harm himself.

Box 1

The authors’ observations

At first we viewed Mr. B’s idea of shooting himself to solve his problems as a delusion (Box 1), but less than 2 weeks later he denied that his self-injury offered any benefit. Because his original belief was transient, we ruled out delusional disorder and major depression with psychotic features.

Some of Mr. B’s symptoms suggested OCD, including thought-related anxiety that is relieved after performing an action—in his case shooting himself. Whereas obsessions and/or compulsions occur daily in OCD, Mr. B would perform the action and then feel fine for months to years before his anxiety resurfaced. Also, he did not consider his thoughts wrong or obtrusive.

 

Box 2

Although Mr. B experienced some depressive symptoms and anxiety just before discharge, we were hesitant to diagnose major depression because his symptoms appeared tied to situational factors. He also did not fit a particular personality disorder, although he showed characteristics of:

• cluster A (odd ideas, solitary lifestyle)
  
• cluster B (self-harm, narcissistic tendencies)
  
• and cluster C (avoiding his relatives, dependence on others to meet his needs).
  

We could have diagnosed personality disorder, not otherwise specified, but we were unsure whether personality explained his pathology or if his personality characteristics warranted diagnosis.

Mr. B’s intentional production of physical symptoms strongly suggested malingering, but we instead diagnosed factitious disorder because he was clearly motivated to play the sick role despite lack of a secondary gain (Box 2). The patient admitted causing the gunshot wound and clearly connected his subsequent emotional relief with both his positive childhood experience in the hospital and his satisfaction after donating a kidney.

Researchers have tried to distinguish between factitious disorder and other types of self-harm. Claes and Vandereycken⁴ would consider Mr. B’s behavior “self-mutilation” rather than factitious. Turner calls DSM-IV-TR criteria for factitious disorder nebulous and says that lying about symptoms or their origin should be a necessary criterion.⁵ If so, then Mr. B’s condition might fit no DSM diagnosis.⁶

The authors’ observations

Although Mr. B’s diagnosis remained elusive, he needed a treatment plan before discharge to prevent another shooting and save his life.

We first considered psychotropics. Because Mr. B’s beliefs did not appear delusional, an antipsychotic would not be a useful first-line treatment. Nor would a benzodiazepine help Mr. B at this point, especially since we did not diagnose primary anxiety.

Although we did not diagnose a major depressive or anxiety-spectrum disorder, we felt an SSRI such as citalopram could help. According to some investigators, SSRIs might benefit patients with over-valued ideas that are not as persistent as delusions.^7,8

Additionally, we felt supportive therapy could help Mr. B establish a therapeutic relationship with a provider to whom he could turn during future crises. Should Mr. B contemplate self-harm, the therapist could suggest medications, hospitalization, or other interventions. We also recommended pastoral counseling to increase his support within his faith.

OUTCOME Another shot?

Before discharge, we start citalopram, 10 mg/d, and schedule a follow-up appointment within 2 weeks. We also suggest that Mr. B:

• move into an apartment near his outpatient doctors
  
• get involved with the local Catholic community to build his support network.
  

When we contact Mr. B 2 months later, he says he discontinued citalopram because he felt no benefit from it. At his initial appointment with a psychiatrist, he denied depressive symptoms and was not scheduled for ongoing therapy. He has not spoken with clergy or other local church members because “I know they would say God has forgiven me.”

Mr. B calls his recent hospitalization upsetting because “I did not get the attention I wanted.” He endorses no immediate plan to shoot himself but voices concern that when his physical problems resolve, he might shoot Himself in the liver—as he had done 40 years ago—to bring himself full circle. “There’s still something attractive about this,” he says.

The authors’ observations

Patients with factitious illness commonly refuse mental health treatment.⁹

We feel Mr. B needs frequent ongoing appointments in a medical clinic where doctors can provide sufficient attention to counter his persistent self-harm urges. Regular appointments with a primary care physician—regardless of whether Mr. B is medically ill—could help him feel supported.

Related resources

• Feldman MD, Eisendrath SJ, eds. The spectrum of factitious disorders. Washington, DC: American Psychiatric Press; 1996.
  
• Sutton J, Martinson D. Self-injury Web site: What self-injury is.www.palace.net/~llama/psych/fwhat.html.
  

Drug brand names

• Citalopram • Celexa
  
• Omeprazole • Prilosec
  

Disclosure

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

CASE: A ‘purification’

Mr. B, age 61, is in the ICU after shooting himself in the abdomen. The trauma team asks our psychiatry consultation/liaison service to determine if he needs special observation to prevent further self-harm.

Two days ago, Mr. B stood in the parking lot of a nearby hospital, aimed his rifle toward the left upper part of his abdomen, and fired. Bleeding profusely, he dragged himself to the hospital’s emergency room. ER staff stabilized him hemodynamically, then transferred him to our hospital’s regional trauma center, where surgeons performed an emergency laparotomy and found 2 sigmoid colon perforations, with feces floating outside the bowel.

After a partial colectomy and colostomy, Mr. B received broad-spectrum antibiotics, narcotic pain medication, and bowel rest in the ICU. When the trauma team called us, the patient’s condition was stable and he had awakened enough to communicate, although he still needed frequent monitoring.

We visit Mr. B in the ICU and ask him why he shot himself. He denies he was attempting suicide but adds that for months he has been feeling depressed, stressed, and guilty about “all the bad things I’ve done in my life.” Shooting himself helped him forget these negative thoughts.

A devout Roman Catholic, Mr. B has been researching flagellation and other forms of physical penance and considers the shooting a purification. He says he shot himself in the abdomen 2 previous times and felt better for months or years after each shooting.

Four years ago, Mr. B donated his left kidney to an unknown recipient. He does not equate the kidney donation with the shootings but says he felt happy while recuperating. He was later disappointed, however, because the procedure did not help him attract the “attention” he had hoped for.

Mr. B says he had been considering the latest shooting for at least 8 months and had carefully planned it. After studying anatomy textbooks, he figured he could fire into the left upper portion of his abdomen without striking a vital organ.

For several evenings, Mr. B aimed his rifle toward his abdomen but could not bring himself to pull the trigger. On the night of the shooting, he said, he “accidentally” fired at a more damaging angle than he had planned.

Cognitive examination results are mostly normal, although Mr. B has trouble interpreting similarities and proverbs. He appears pale but well-nourished, well-groomed, and serene. He speaks softly, often closing his eyes or staring into the distance. He says he feels “relieved” and “happy” after the shooting but did not anticipate such a severe injury. He denies suicidal thoughts and—because of his current euphoric mood—he hopes he never “needs” to shoot himself again.

The authors’ observations

We first considered delusional disorder and major depressive disorder with psychotic features. Mr. B’s belief that shooting himself would solve his problems seemed delusional, although he did not appear psychotic otherwise. Confusingly, Mr. B’s pre-admission symptoms seemed to suggest major depressive disorder, but he was happy in the ICU.

We explored other diagnoses, such as an odd form of OCD and a personality disorder (especially cluster A, given his strange beliefs), though at this point we had too little information for either diagnosis.

We also wondered if Mr. B’s behavior was normal given his strong belief in Catholic penance. Although some sects of the Catholic Church practice self-flagellation and other forms of self-punishment,^1-3 we found no evidence that the church condones or encourages self-shooting. Moreover, Mr. B admitted during questioning that a Catholic clergy member told him shooting oneself is not an appropriate penance.

The authors’ observations

Mr. B was recovering from major abdominal surgery, was taking nothing orally, and claimed to feel fine psychologically. Because he was not grossly psychotic and did not endorse anxiety or depression, we decided against medication but recommended a chaplain consult and planned to visit Mr. B daily to gather more history.

We considered Mr. B a low suicide risk—especially while hospitalized—after he said his “need” to shoot himself had dissipated. He also endorsed no suicidal thoughts or other depressive symptoms, and the nursing staff viewed him as pleasant and compliant. We noted this evidence in the chart and continued to reassess him daily.

HISTORY: Dreams, nightmares

Over the next week, Mr. B shares his life story. He says his parents divorced when he was age 5, and around that time he spent approximately 2 weeks in the hospital after being hit by a truck. He considers those 2 weeks a bright spot in an otherwise turbulent childhood because his parents did not fight and he was showered with gifts and attention.

 

Soon after, Mr. B lived with his mother. When he was 9, he heard his divorced parents arguing during a family gathering and prayed for his own death.

Throughout his childhood, Mr. B dreamed of becoming a priest and a war hero. In his early teens, he attended a church youth program where he and other youths were taught that masturbation is a mortal sin. Through high school, Mr. B’s inability to stop masturbating shook his faith and discouraged him from pursuing the priesthood.

In high school, Mr. B did not use alcohol or drugs and excelled academically but had few friends. After graduating, he enlisted in the U.S. Army and hoped to serve in Vietnam, but basic training became too stressful. The relentless harangues from drill instructors reminded him of his parents’ frequent shouting matches during his childhood.

Approximately 2 weeks into basic training, Mr. B shot himself in the abdomen and injured his liver. He underwent laparotomy and cholecystectomy and was discharged from the military. His anxiety dissipated as he recovered, though he later regretted not serving in Vietnam.

Mr. B married at age 44 and was divorced 13 years later. Throughout the marriage, he says, he verbally abused his wife and was emotionally unsupportive. After the divorce, he felt remorse over having mistreated her. His guilt disappeared after he donated his left kidney to an unknown recipient, but the guilt soon returned and drove him to shoot himself a second time in 2005.

Mr. B worked as a special education teacher for 20 years before retiring 4 years ago and has since been pursuing a similar position because he misses going to work. His inability to find a permanent job has led to anxiety, insomnia, increased guilt, and decreased appetite. He says these feelings fueled his desire to shoot himself a third time.

Since his divorce, Mr. B has lived alone and has no family or friends nearby. He feels isolated and is hurt that his family has not acknowledged the cards and notes he sent to them but adds that he did not include his return address on the mailings.

FOLLOW-UP: No relief

After 1 week in the ICU, Mr. B is transferred to the surgical ward. His condition is fair and he continues to receive IV antibiotics; analgesics as needed; omeprazole, 20 mg/d, to prevent a stress ulcer; bowel care medications; and ostomy care and education. We continue to visit him in the surgical ward almost daily. He seems to enjoy our visits, during which he openly discusses his past.

Eleven days after admission, Mr. B says shooting himself has not relieved his negative feelings, and his impending discharge makes him feel anxious with some suicidal thoughts. The surgical team delays discharge after Mr. B develops ileus with nausea and vomiting. The trauma team’s attending physician prescribes an antiemetic, and ileus resolves after 4 days. Mr. B then is discharged in stable condition after he denies intention to harm himself.

Box 1

The authors’ observations

At first we viewed Mr. B’s idea of shooting himself to solve his problems as a delusion (Box 1), but less than 2 weeks later he denied that his self-injury offered any benefit. Because his original belief was transient, we ruled out delusional disorder and major depression with psychotic features.

Some of Mr. B’s symptoms suggested OCD, including thought-related anxiety that is relieved after performing an action—in his case shooting himself. Whereas obsessions and/or compulsions occur daily in OCD, Mr. B would perform the action and then feel fine for months to years before his anxiety resurfaced. Also, he did not consider his thoughts wrong or obtrusive.

 

Box 2

Although Mr. B experienced some depressive symptoms and anxiety just before discharge, we were hesitant to diagnose major depression because his symptoms appeared tied to situational factors. He also did not fit a particular personality disorder, although he showed characteristics of:

• cluster A (odd ideas, solitary lifestyle)
  
• cluster B (self-harm, narcissistic tendencies)
  
• and cluster C (avoiding his relatives, dependence on others to meet his needs).
  

We could have diagnosed personality disorder, not otherwise specified, but we were unsure whether personality explained his pathology or if his personality characteristics warranted diagnosis.

Mr. B’s intentional production of physical symptoms strongly suggested malingering, but we instead diagnosed factitious disorder because he was clearly motivated to play the sick role despite lack of a secondary gain (Box 2). The patient admitted causing the gunshot wound and clearly connected his subsequent emotional relief with both his positive childhood experience in the hospital and his satisfaction after donating a kidney.

Researchers have tried to distinguish between factitious disorder and other types of self-harm. Claes and Vandereycken⁴ would consider Mr. B’s behavior “self-mutilation” rather than factitious. Turner calls DSM-IV-TR criteria for factitious disorder nebulous and says that lying about symptoms or their origin should be a necessary criterion.⁵ If so, then Mr. B’s condition might fit no DSM diagnosis.⁶

The authors’ observations

Although Mr. B’s diagnosis remained elusive, he needed a treatment plan before discharge to prevent another shooting and save his life.

We first considered psychotropics. Because Mr. B’s beliefs did not appear delusional, an antipsychotic would not be a useful first-line treatment. Nor would a benzodiazepine help Mr. B at this point, especially since we did not diagnose primary anxiety.

Although we did not diagnose a major depressive or anxiety-spectrum disorder, we felt an SSRI such as citalopram could help. According to some investigators, SSRIs might benefit patients with over-valued ideas that are not as persistent as delusions.^7,8

Additionally, we felt supportive therapy could help Mr. B establish a therapeutic relationship with a provider to whom he could turn during future crises. Should Mr. B contemplate self-harm, the therapist could suggest medications, hospitalization, or other interventions. We also recommended pastoral counseling to increase his support within his faith.

OUTCOME Another shot?

Before discharge, we start citalopram, 10 mg/d, and schedule a follow-up appointment within 2 weeks. We also suggest that Mr. B:

• move into an apartment near his outpatient doctors
  
• get involved with the local Catholic community to build his support network.
  

When we contact Mr. B 2 months later, he says he discontinued citalopram because he felt no benefit from it. At his initial appointment with a psychiatrist, he denied depressive symptoms and was not scheduled for ongoing therapy. He has not spoken with clergy or other local church members because “I know they would say God has forgiven me.”

Mr. B calls his recent hospitalization upsetting because “I did not get the attention I wanted.” He endorses no immediate plan to shoot himself but voices concern that when his physical problems resolve, he might shoot Himself in the liver—as he had done 40 years ago—to bring himself full circle. “There’s still something attractive about this,” he says.

The authors’ observations

Patients with factitious illness commonly refuse mental health treatment.⁹

We feel Mr. B needs frequent ongoing appointments in a medical clinic where doctors can provide sufficient attention to counter his persistent self-harm urges. Regular appointments with a primary care physician—regardless of whether Mr. B is medically ill—could help him feel supported.

Related resources

• Feldman MD, Eisendrath SJ, eds. The spectrum of factitious disorders. Washington, DC: American Psychiatric Press; 1996.
  
• Sutton J, Martinson D. Self-injury Web site: What self-injury is.www.palace.net/~llama/psych/fwhat.html.
  

Drug brand names

• Citalopram • Celexa
  
• Omeprazole • Prilosec
  

Disclosure

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

CASE: A ‘purification’

Mr. B, age 61, is in the ICU after shooting himself in the abdomen. The trauma team asks our psychiatry consultation/liaison service to determine if he needs special observation to prevent further self-harm.

Two days ago, Mr. B stood in the parking lot of a nearby hospital, aimed his rifle toward the left upper part of his abdomen, and fired. Bleeding profusely, he dragged himself to the hospital’s emergency room. ER staff stabilized him hemodynamically, then transferred him to our hospital’s regional trauma center, where surgeons performed an emergency laparotomy and found 2 sigmoid colon perforations, with feces floating outside the bowel.

After a partial colectomy and colostomy, Mr. B received broad-spectrum antibiotics, narcotic pain medication, and bowel rest in the ICU. When the trauma team called us, the patient’s condition was stable and he had awakened enough to communicate, although he still needed frequent monitoring.

We visit Mr. B in the ICU and ask him why he shot himself. He denies he was attempting suicide but adds that for months he has been feeling depressed, stressed, and guilty about “all the bad things I’ve done in my life.” Shooting himself helped him forget these negative thoughts.

A devout Roman Catholic, Mr. B has been researching flagellation and other forms of physical penance and considers the shooting a purification. He says he shot himself in the abdomen 2 previous times and felt better for months or years after each shooting.

Four years ago, Mr. B donated his left kidney to an unknown recipient. He does not equate the kidney donation with the shootings but says he felt happy while recuperating. He was later disappointed, however, because the procedure did not help him attract the “attention” he had hoped for.

Mr. B says he had been considering the latest shooting for at least 8 months and had carefully planned it. After studying anatomy textbooks, he figured he could fire into the left upper portion of his abdomen without striking a vital organ.

For several evenings, Mr. B aimed his rifle toward his abdomen but could not bring himself to pull the trigger. On the night of the shooting, he said, he “accidentally” fired at a more damaging angle than he had planned.

Cognitive examination results are mostly normal, although Mr. B has trouble interpreting similarities and proverbs. He appears pale but well-nourished, well-groomed, and serene. He speaks softly, often closing his eyes or staring into the distance. He says he feels “relieved” and “happy” after the shooting but did not anticipate such a severe injury. He denies suicidal thoughts and—because of his current euphoric mood—he hopes he never “needs” to shoot himself again.

The authors’ observations

We first considered delusional disorder and major depressive disorder with psychotic features. Mr. B’s belief that shooting himself would solve his problems seemed delusional, although he did not appear psychotic otherwise. Confusingly, Mr. B’s pre-admission symptoms seemed to suggest major depressive disorder, but he was happy in the ICU.

We explored other diagnoses, such as an odd form of OCD and a personality disorder (especially cluster A, given his strange beliefs), though at this point we had too little information for either diagnosis.

We also wondered if Mr. B’s behavior was normal given his strong belief in Catholic penance. Although some sects of the Catholic Church practice self-flagellation and other forms of self-punishment,^1-3 we found no evidence that the church condones or encourages self-shooting. Moreover, Mr. B admitted during questioning that a Catholic clergy member told him shooting oneself is not an appropriate penance.

The authors’ observations

Mr. B was recovering from major abdominal surgery, was taking nothing orally, and claimed to feel fine psychologically. Because he was not grossly psychotic and did not endorse anxiety or depression, we decided against medication but recommended a chaplain consult and planned to visit Mr. B daily to gather more history.

We considered Mr. B a low suicide risk—especially while hospitalized—after he said his “need” to shoot himself had dissipated. He also endorsed no suicidal thoughts or other depressive symptoms, and the nursing staff viewed him as pleasant and compliant. We noted this evidence in the chart and continued to reassess him daily.

HISTORY: Dreams, nightmares

Over the next week, Mr. B shares his life story. He says his parents divorced when he was age 5, and around that time he spent approximately 2 weeks in the hospital after being hit by a truck. He considers those 2 weeks a bright spot in an otherwise turbulent childhood because his parents did not fight and he was showered with gifts and attention.

 

Soon after, Mr. B lived with his mother. When he was 9, he heard his divorced parents arguing during a family gathering and prayed for his own death.

Throughout his childhood, Mr. B dreamed of becoming a priest and a war hero. In his early teens, he attended a church youth program where he and other youths were taught that masturbation is a mortal sin. Through high school, Mr. B’s inability to stop masturbating shook his faith and discouraged him from pursuing the priesthood.

In high school, Mr. B did not use alcohol or drugs and excelled academically but had few friends. After graduating, he enlisted in the U.S. Army and hoped to serve in Vietnam, but basic training became too stressful. The relentless harangues from drill instructors reminded him of his parents’ frequent shouting matches during his childhood.

Approximately 2 weeks into basic training, Mr. B shot himself in the abdomen and injured his liver. He underwent laparotomy and cholecystectomy and was discharged from the military. His anxiety dissipated as he recovered, though he later regretted not serving in Vietnam.

Mr. B married at age 44 and was divorced 13 years later. Throughout the marriage, he says, he verbally abused his wife and was emotionally unsupportive. After the divorce, he felt remorse over having mistreated her. His guilt disappeared after he donated his left kidney to an unknown recipient, but the guilt soon returned and drove him to shoot himself a second time in 2005.

Mr. B worked as a special education teacher for 20 years before retiring 4 years ago and has since been pursuing a similar position because he misses going to work. His inability to find a permanent job has led to anxiety, insomnia, increased guilt, and decreased appetite. He says these feelings fueled his desire to shoot himself a third time.

Since his divorce, Mr. B has lived alone and has no family or friends nearby. He feels isolated and is hurt that his family has not acknowledged the cards and notes he sent to them but adds that he did not include his return address on the mailings.

FOLLOW-UP: No relief

After 1 week in the ICU, Mr. B is transferred to the surgical ward. His condition is fair and he continues to receive IV antibiotics; analgesics as needed; omeprazole, 20 mg/d, to prevent a stress ulcer; bowel care medications; and ostomy care and education. We continue to visit him in the surgical ward almost daily. He seems to enjoy our visits, during which he openly discusses his past.

Eleven days after admission, Mr. B says shooting himself has not relieved his negative feelings, and his impending discharge makes him feel anxious with some suicidal thoughts. The surgical team delays discharge after Mr. B develops ileus with nausea and vomiting. The trauma team’s attending physician prescribes an antiemetic, and ileus resolves after 4 days. Mr. B then is discharged in stable condition after he denies intention to harm himself.

Box 1

The authors’ observations

At first we viewed Mr. B’s idea of shooting himself to solve his problems as a delusion (Box 1), but less than 2 weeks later he denied that his self-injury offered any benefit. Because his original belief was transient, we ruled out delusional disorder and major depression with psychotic features.

Some of Mr. B’s symptoms suggested OCD, including thought-related anxiety that is relieved after performing an action—in his case shooting himself. Whereas obsessions and/or compulsions occur daily in OCD, Mr. B would perform the action and then feel fine for months to years before his anxiety resurfaced. Also, he did not consider his thoughts wrong or obtrusive.

 

Box 2

Although Mr. B experienced some depressive symptoms and anxiety just before discharge, we were hesitant to diagnose major depression because his symptoms appeared tied to situational factors. He also did not fit a particular personality disorder, although he showed characteristics of:

• cluster A (odd ideas, solitary lifestyle)
  
• cluster B (self-harm, narcissistic tendencies)
  
• and cluster C (avoiding his relatives, dependence on others to meet his needs).
  

We could have diagnosed personality disorder, not otherwise specified, but we were unsure whether personality explained his pathology or if his personality characteristics warranted diagnosis.

Mr. B’s intentional production of physical symptoms strongly suggested malingering, but we instead diagnosed factitious disorder because he was clearly motivated to play the sick role despite lack of a secondary gain (Box 2). The patient admitted causing the gunshot wound and clearly connected his subsequent emotional relief with both his positive childhood experience in the hospital and his satisfaction after donating a kidney.

Researchers have tried to distinguish between factitious disorder and other types of self-harm. Claes and Vandereycken⁴ would consider Mr. B’s behavior “self-mutilation” rather than factitious. Turner calls DSM-IV-TR criteria for factitious disorder nebulous and says that lying about symptoms or their origin should be a necessary criterion.⁵ If so, then Mr. B’s condition might fit no DSM diagnosis.⁶

The authors’ observations

Although Mr. B’s diagnosis remained elusive, he needed a treatment plan before discharge to prevent another shooting and save his life.

We first considered psychotropics. Because Mr. B’s beliefs did not appear delusional, an antipsychotic would not be a useful first-line treatment. Nor would a benzodiazepine help Mr. B at this point, especially since we did not diagnose primary anxiety.

Although we did not diagnose a major depressive or anxiety-spectrum disorder, we felt an SSRI such as citalopram could help. According to some investigators, SSRIs might benefit patients with over-valued ideas that are not as persistent as delusions.^7,8

Additionally, we felt supportive therapy could help Mr. B establish a therapeutic relationship with a provider to whom he could turn during future crises. Should Mr. B contemplate self-harm, the therapist could suggest medications, hospitalization, or other interventions. We also recommended pastoral counseling to increase his support within his faith.

OUTCOME Another shot?

Before discharge, we start citalopram, 10 mg/d, and schedule a follow-up appointment within 2 weeks. We also suggest that Mr. B:

• move into an apartment near his outpatient doctors
  
• get involved with the local Catholic community to build his support network.
  

When we contact Mr. B 2 months later, he says he discontinued citalopram because he felt no benefit from it. At his initial appointment with a psychiatrist, he denied depressive symptoms and was not scheduled for ongoing therapy. He has not spoken with clergy or other local church members because “I know they would say God has forgiven me.”

Mr. B calls his recent hospitalization upsetting because “I did not get the attention I wanted.” He endorses no immediate plan to shoot himself but voices concern that when his physical problems resolve, he might shoot Himself in the liver—as he had done 40 years ago—to bring himself full circle. “There’s still something attractive about this,” he says.

The authors’ observations

Patients with factitious illness commonly refuse mental health treatment.⁹

We feel Mr. B needs frequent ongoing appointments in a medical clinic where doctors can provide sufficient attention to counter his persistent self-harm urges. Regular appointments with a primary care physician—regardless of whether Mr. B is medically ill—could help him feel supported.

Related resources

• Feldman MD, Eisendrath SJ, eds. The spectrum of factitious disorders. Washington, DC: American Psychiatric Press; 1996.
  
• Sutton J, Martinson D. Self-injury Web site: What self-injury is.www.palace.net/~llama/psych/fwhat.html.
  

Drug brand names

• Citalopram • Celexa
  
• Omeprazole • Prilosec
  

Disclosure

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

CASE: The man from Betelgeuse

Mr. F, age 33, has been hospitalized repeatedly for psychotic episodes after abuse of dextromethorphan in cold medications.

Approximately 1 week before presenting to us, Mr. F stormed out of his house after his father, with whom he lived, confronted him about spending his allowance on cold medications. He spent the week living on the streets, abusing dextromethorphan whenever he could get it.

One night, Mr. F approached a police officer at an accident scene and exclaimed, “Dude, I’m from the planet Betelgeuse.” He appeared disorganized as police questioned him, and officers transported him to the county hospital’s psychiatric emergency service.

At presentation, Mr. F is at times silly, irritable, and sleepy, and chants incantations during the intake interview. Alternately, he hears Jesus Christ and aliens from Betelgeuse telling him “everything is going to be cool” and voices of aliens threatening to abduct him.

We admit Mr. F to the inpatient psychiatric unit, start risperidone at 2 mg nightly, and titrate it to 6 mg nightly over 3 days, after which he is significantly more organized with reduced auditory hallucinations. At discharge 6 days later, he still occasionally hears Jesus but has partial insight into his obsession with aliens and no paranoid delusions. We continue risperidone, 6 mg nightly, and refer him to an outpatient mental health program. He visits the clinic once but avoids the attending psychiatrist.

Five days later, Mr. F begins hallucinating at home and his father brings him back to the emergency psychiatry unit. At presentation, the patient claims to be an agent of Satan and waves his arms wildly while performing “black magic.” He believes he is damned and that previous messages he thought came from Jesus and extraterrestrials were instead from the devil.

Mr. F’s father reports that over the weekend his son ingested 6 boxes of cold medicine—each with 16 tablets containing 30 mg of dextromethorphan. Peeling skin on the lower part of Mr. F’s forehead, the bridge of his nose, and under his eyes suggests chronic cold tablet abuse. We re-admit the patient after extended urine drug screen shows traces of chlorpheniramine.

The authors’ observations

Routine urine drug screens based on radio-immunoassay detect many substances, but an extended or comprehensive urine drug screen based on gas chromatography-mass spectrometry is needed to detect dextromethorphan.¹ Tertiary hospitals and reference laboratories usually offer these tests.

An extended urine screen will not detect dextromethorphan 24 hours after use because the agent has a 3- to 11-hour half-life. The test can, however, detect other active cold preparation compounds with longer half-lives, such as chlorpheniramine.

If extended urine screening is not available, clinical findings discussed later in this article can confirm recent cold medication abuse. Blood testing can reveal dextromethorphan levels, but a 3- to 6-mL sample may be needed.

HISTORY: ‘Sick’ at 16

Mr. F began abusing dextromethorphan at age 16, when friends would “turn him on” to 8-ounce bottles of cough syrup every other week. He later tried marijuana, cocaine, phencyclidine, methamphetamine, morphine, and LSD. Soon after graduating from high school, he stopped using substances and remained clean for several years.

At age 25, Mr. F suffered his first psychotic break, after which a psychiatrist diagnosed schizophrenia. Initial symptom control with antipsychotics helped him finish college.

Mr. F worked as a restaurant manager for about 4 months but found the job stressful and constantly argued with staff. He resumed abusing cough syrup to relieve his stress but soon became hooked on its dissociative and hallucinogenic effects. One night he ingested enough cough syrup to remain “high” until the next morning. He was hallucinating when he reported to work that day and was fired.

Since then, Mr. F’s cold medication abuse has escalated from biweekly to almost daily at presentation. He switched to tablets because the syrup induced cold symptoms and he finds the “buzz” from the tablets easier to control.

He typically dresses in black (in keeping with his satanic obsessions) and wears a long black overcoat with several pockets, that allows him to carry boxes of cold capsules, books, and other items.

Mr. F’s father has repeatedly tried to stop his son’s cold tablet abuse by cutting off his allowance. Dextromethorphan-containing cold medications are inexpensive, however—a box of 16 30-mg tablets costs as little as $1.50. Also, Mr. F often would get money for cold capsules by going to malls and participating in market research surveys.

 

In the past year, Mr. F was hospitalized 6 times after dextromethorphan-induced psychotic decompensations. He has been unemployed for more than 5 years, has not been in a serious romantic relationship since college, and depends on his father for financial support. He is not abusing other substances.

The authors’ observations

As many as 80% of patients with schizophrenia also have a substance abuse disorder.² Access to psychoactive substances, kindling associated with schizophrenia, and attempts to stop hallucinations with alcohol or illicit drugs may explain this high prevalence.² Also, genetic or phenotypic vulnerability in schizophrenia might alter the mesolimbic dopamine system that moderates reward.

Compared with patients with schizophrenia who are substance-free, comorbid substance abuse in schizophrenia increases:

• severity of psychotic symptoms
  
• likelihood of emergency service use
  
• risk of suicide, illness, injury, hospitalization, or incarceration.³
  

Box 1

Whereas alcohol, marijuana, and cocaine abuse are common in schizophrenia,² to our knowledge only 2 other cases of comorbid dextromethorphan dependence and schizophrenia have been reported.^4,5

Mr. F responded well to risperidone when he wasn’t abusing cold tablets. After his last hospitalization, we referred him to a comprehensive outpatient program that could have addressed his cold medicine abuse and reintegrated him into the workplace. He avoided seeing the clinic psychiatrist, however, after promising his case manager that he would stop abusing dextromethorphan.

TREATMENT: Back to Betelgeuse

Upon re-admission, we restart risperidone, 6 mg nightly. Mr. F shows extreme somnolence caused by massive cold capsule use and is minimally cooperative with the psychiatrist’s follow-up interview. Over 36 hours, he awakens only for meals and medication and to use the bathroom. Once the somnolence passes, he cannot fall asleep at night.

Six days after admission, Mr. F is organized and hears voices mostly from Jesus with some demonic delusions. Extended urine drug screen taken 3 days after admission shows traces of chlorpheniramine but no dextromethorphan.

By day 7, Mr. F is nearly free of delusions and is discharged the next day. We continue risperidone, 6 mg nightly, to prevent the “voices,” and add diphenhydramine, 50 mg nightly, to regulate his sleep. We arrange follow-up care at an outpatient clinic, but Mr. F again avoids the clinic psychiatrist.

The authors’ observations

Mr. F’s “robo” binge triggered a profound and prolonged psychotic decompensation.

Dextrorphan—a pharmacologically active metabolite of dextromethorphan— might have disrupted cortical and sub-cortical glutamatergic neurotransmission,⁶ leading to florid psychosis and delayed recovery. Induction of the cytochrome P-450 2D6 isoenzyme, which metabolizes dextromethorphan, also could have prolonged Mr. F’s psychosis (Box 1).^7-11

RELAPSE: Return visits

Three weeks after discharge, Mr. F fights with police officers after they find him hallucinating in the streets. Police charge him with disorderly conduct and resisting arrest and bring him back to the psychiatric ER. We again resolve his auditory hallucinations with risperidone, 6 mg nightly. After 8 days we discharge him to police, who then transport him to jail and later release him on bail.

Six months later, Mr. F is hospitalized twice in 2 months after dextromethorphan-induced decompensations. He recovers quickly both times but lacks insight into his mental illness and his “robo” problem.

The authors’ observations

Dextromethorphan, known by many street names (Box 2), is contained in more than 100 OTC preparations, and is sold on the Internet in powder form.

Abuse of dextromethorphan-containing preparations is rising among teenagers and young adults. Nonmedical “robo” use led to 5,581 ER visits in the United States in 2004,¹² and California reported a 10-fold rise in dextromethorphan abuse among teenagers from 1999 to 2004.

 

¹³ Numerous factors explain this increase:

• Most people do not know that dextromethorphan-laced medications are dangerous if misused.
  
• These preparations can be purchased at many stores or snatched from the medicine chest.
  
• Several Web sites describe how to “safely” abuse dextromethorphan.¹³
  

Further, some pediatricians, family physicians, emergency physicians, and psychiatrists do not suspect “robo” abuse, in part because ordinary urine drug screens do not detect dextromethorphan.

medical consequences

Many dextromethorphan-laced preparations contain other active compounds—such as pseudoephedrine, acetaminophen, chlorpheniramine, guaifenesin, or bromide—that can cause serious adverse effects at above-normal doses. Abuse of medications containing both chlorpheniramine and dextromethorphan leads to hallucinogenic euphoria and dissociation, followed by hours of intense somnolence.

Dextromethorphan can cause serotonin syndrome when taken with serotonergic drugs such as amphetamines, cocaine, monoamine oxidase inhibitors, or selective serotonin reuptake inhibitors. Symptoms include tachycardia, hypertension, diaphoresis, mydriasis, myoclonus, agitation, and seizures.

Box 2

The authors’ observations

Physical and psychiatric symptoms, patient history, and collateral information together can confirm dextromethorphan abuse in patients who present with mainly visual and tactile hallucinations. The signs are easy to miss in patients with schizophrenia because schizophrenia is believed to be causing the psychosis.

Psychiatric/physical symptoms. Psychiatric symptoms of “robo” intoxication include euphoria, altered time perception, disorientation, and tactile, visual and auditory hallucinations.⁷ Physical symptoms include excitation, nystagmus, tachycardia, hypertension, hyperthermia, vomiting, urinary retention, drowsiness, and rash. Extreme dextromethorphan withdrawal can cause dysphoria, insomnia, vomiting, diaphoresis, abdominal pain, and diarrhea.⁷

Psychiatric symptoms of intoxication with dextromethorphan or phencyclidine are similar, but phencyclidine-intoxicated patients typically present with fluctuating behavior and motor symptoms including tremor, dystonic reactions, and catalepsy.

Also watch for dermatitis on the forehead, nose, or cheeks, which can result from chronic abuse of preparations containing dextromethorphan plus bromide or chlorpheniramine.

Patient history. Has the patient abused dextromethorphan before? If so, how often? When was he last treated for decompensation after cold medication abuse?

Also check for abuse of other substances, and ask teenage patients if their friends use cold preparations recreationally.

Collateral information. Ask family members to search the patient’s room for supplies of cold medicine and for empty boxes and capsule cards, check the medicine chest regularly to see if cold medications are missing, and check the patient’s jacket or coat pockets for cold tablets or cough syrup.

Treating ‘robo’ abuse

Convincing the patient and family that dextromethorphan abuse can cause severe harm is critical to promoting a positive outcome. Referral to a substance abuse rehabilitation program or 12-step group can help.

Related resources

• U.S. Department of Justice, National Drug Intelligence Center. Intelligence bulletin: DXM (dextromethorphan). www.usdoj.gov/ndic/pubs11/11563/index.htm.
  
• Partnership for a Drug-Free America. Resource for parents. www.drugfree.org/Parent. Click on “Cough Medicine Abuse” under “Special Drug Reports.”
  
• U.S. Food and Drug Administraton. FDA warns against abuse of dextromethorphan (DXM). www.fda.gov, enter “dextromethorphan” in search field.
  

Drug brand names

• Risperidone • Risperdal
  

Disclosure

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

CASE: The man from Betelgeuse

Mr. F, age 33, has been hospitalized repeatedly for psychotic episodes after abuse of dextromethorphan in cold medications.

Approximately 1 week before presenting to us, Mr. F stormed out of his house after his father, with whom he lived, confronted him about spending his allowance on cold medications. He spent the week living on the streets, abusing dextromethorphan whenever he could get it.

One night, Mr. F approached a police officer at an accident scene and exclaimed, “Dude, I’m from the planet Betelgeuse.” He appeared disorganized as police questioned him, and officers transported him to the county hospital’s psychiatric emergency service.

At presentation, Mr. F is at times silly, irritable, and sleepy, and chants incantations during the intake interview. Alternately, he hears Jesus Christ and aliens from Betelgeuse telling him “everything is going to be cool” and voices of aliens threatening to abduct him.

We admit Mr. F to the inpatient psychiatric unit, start risperidone at 2 mg nightly, and titrate it to 6 mg nightly over 3 days, after which he is significantly more organized with reduced auditory hallucinations. At discharge 6 days later, he still occasionally hears Jesus but has partial insight into his obsession with aliens and no paranoid delusions. We continue risperidone, 6 mg nightly, and refer him to an outpatient mental health program. He visits the clinic once but avoids the attending psychiatrist.

Five days later, Mr. F begins hallucinating at home and his father brings him back to the emergency psychiatry unit. At presentation, the patient claims to be an agent of Satan and waves his arms wildly while performing “black magic.” He believes he is damned and that previous messages he thought came from Jesus and extraterrestrials were instead from the devil.

Mr. F’s father reports that over the weekend his son ingested 6 boxes of cold medicine—each with 16 tablets containing 30 mg of dextromethorphan. Peeling skin on the lower part of Mr. F’s forehead, the bridge of his nose, and under his eyes suggests chronic cold tablet abuse. We re-admit the patient after extended urine drug screen shows traces of chlorpheniramine.

The authors’ observations

Routine urine drug screens based on radio-immunoassay detect many substances, but an extended or comprehensive urine drug screen based on gas chromatography-mass spectrometry is needed to detect dextromethorphan.¹ Tertiary hospitals and reference laboratories usually offer these tests.

An extended urine screen will not detect dextromethorphan 24 hours after use because the agent has a 3- to 11-hour half-life. The test can, however, detect other active cold preparation compounds with longer half-lives, such as chlorpheniramine.

If extended urine screening is not available, clinical findings discussed later in this article can confirm recent cold medication abuse. Blood testing can reveal dextromethorphan levels, but a 3- to 6-mL sample may be needed.

HISTORY: ‘Sick’ at 16

Mr. F began abusing dextromethorphan at age 16, when friends would “turn him on” to 8-ounce bottles of cough syrup every other week. He later tried marijuana, cocaine, phencyclidine, methamphetamine, morphine, and LSD. Soon after graduating from high school, he stopped using substances and remained clean for several years.

At age 25, Mr. F suffered his first psychotic break, after which a psychiatrist diagnosed schizophrenia. Initial symptom control with antipsychotics helped him finish college.

Mr. F worked as a restaurant manager for about 4 months but found the job stressful and constantly argued with staff. He resumed abusing cough syrup to relieve his stress but soon became hooked on its dissociative and hallucinogenic effects. One night he ingested enough cough syrup to remain “high” until the next morning. He was hallucinating when he reported to work that day and was fired.

Since then, Mr. F’s cold medication abuse has escalated from biweekly to almost daily at presentation. He switched to tablets because the syrup induced cold symptoms and he finds the “buzz” from the tablets easier to control.

He typically dresses in black (in keeping with his satanic obsessions) and wears a long black overcoat with several pockets, that allows him to carry boxes of cold capsules, books, and other items.

Mr. F’s father has repeatedly tried to stop his son’s cold tablet abuse by cutting off his allowance. Dextromethorphan-containing cold medications are inexpensive, however—a box of 16 30-mg tablets costs as little as $1.50. Also, Mr. F often would get money for cold capsules by going to malls and participating in market research surveys.

 

In the past year, Mr. F was hospitalized 6 times after dextromethorphan-induced psychotic decompensations. He has been unemployed for more than 5 years, has not been in a serious romantic relationship since college, and depends on his father for financial support. He is not abusing other substances.

The authors’ observations

As many as 80% of patients with schizophrenia also have a substance abuse disorder.² Access to psychoactive substances, kindling associated with schizophrenia, and attempts to stop hallucinations with alcohol or illicit drugs may explain this high prevalence.² Also, genetic or phenotypic vulnerability in schizophrenia might alter the mesolimbic dopamine system that moderates reward.

Compared with patients with schizophrenia who are substance-free, comorbid substance abuse in schizophrenia increases:

• severity of psychotic symptoms
  
• likelihood of emergency service use
  
• risk of suicide, illness, injury, hospitalization, or incarceration.³
  

Box 1

Whereas alcohol, marijuana, and cocaine abuse are common in schizophrenia,² to our knowledge only 2 other cases of comorbid dextromethorphan dependence and schizophrenia have been reported.^4,5

Mr. F responded well to risperidone when he wasn’t abusing cold tablets. After his last hospitalization, we referred him to a comprehensive outpatient program that could have addressed his cold medicine abuse and reintegrated him into the workplace. He avoided seeing the clinic psychiatrist, however, after promising his case manager that he would stop abusing dextromethorphan.

TREATMENT: Back to Betelgeuse

Upon re-admission, we restart risperidone, 6 mg nightly. Mr. F shows extreme somnolence caused by massive cold capsule use and is minimally cooperative with the psychiatrist’s follow-up interview. Over 36 hours, he awakens only for meals and medication and to use the bathroom. Once the somnolence passes, he cannot fall asleep at night.

Six days after admission, Mr. F is organized and hears voices mostly from Jesus with some demonic delusions. Extended urine drug screen taken 3 days after admission shows traces of chlorpheniramine but no dextromethorphan.

By day 7, Mr. F is nearly free of delusions and is discharged the next day. We continue risperidone, 6 mg nightly, to prevent the “voices,” and add diphenhydramine, 50 mg nightly, to regulate his sleep. We arrange follow-up care at an outpatient clinic, but Mr. F again avoids the clinic psychiatrist.

The authors’ observations

Mr. F’s “robo” binge triggered a profound and prolonged psychotic decompensation.

Dextrorphan—a pharmacologically active metabolite of dextromethorphan— might have disrupted cortical and sub-cortical glutamatergic neurotransmission,⁶ leading to florid psychosis and delayed recovery. Induction of the cytochrome P-450 2D6 isoenzyme, which metabolizes dextromethorphan, also could have prolonged Mr. F’s psychosis (Box 1).^7-11

RELAPSE: Return visits

Three weeks after discharge, Mr. F fights with police officers after they find him hallucinating in the streets. Police charge him with disorderly conduct and resisting arrest and bring him back to the psychiatric ER. We again resolve his auditory hallucinations with risperidone, 6 mg nightly. After 8 days we discharge him to police, who then transport him to jail and later release him on bail.

Six months later, Mr. F is hospitalized twice in 2 months after dextromethorphan-induced decompensations. He recovers quickly both times but lacks insight into his mental illness and his “robo” problem.

The authors’ observations

Dextromethorphan, known by many street names (Box 2), is contained in more than 100 OTC preparations, and is sold on the Internet in powder form.

Abuse of dextromethorphan-containing preparations is rising among teenagers and young adults. Nonmedical “robo” use led to 5,581 ER visits in the United States in 2004,¹² and California reported a 10-fold rise in dextromethorphan abuse among teenagers from 1999 to 2004.

 

¹³ Numerous factors explain this increase:

• Most people do not know that dextromethorphan-laced medications are dangerous if misused.
  
• These preparations can be purchased at many stores or snatched from the medicine chest.
  
• Several Web sites describe how to “safely” abuse dextromethorphan.¹³
  

Further, some pediatricians, family physicians, emergency physicians, and psychiatrists do not suspect “robo” abuse, in part because ordinary urine drug screens do not detect dextromethorphan.

medical consequences

Many dextromethorphan-laced preparations contain other active compounds—such as pseudoephedrine, acetaminophen, chlorpheniramine, guaifenesin, or bromide—that can cause serious adverse effects at above-normal doses. Abuse of medications containing both chlorpheniramine and dextromethorphan leads to hallucinogenic euphoria and dissociation, followed by hours of intense somnolence.

Dextromethorphan can cause serotonin syndrome when taken with serotonergic drugs such as amphetamines, cocaine, monoamine oxidase inhibitors, or selective serotonin reuptake inhibitors. Symptoms include tachycardia, hypertension, diaphoresis, mydriasis, myoclonus, agitation, and seizures.

Box 2

The authors’ observations

Physical and psychiatric symptoms, patient history, and collateral information together can confirm dextromethorphan abuse in patients who present with mainly visual and tactile hallucinations. The signs are easy to miss in patients with schizophrenia because schizophrenia is believed to be causing the psychosis.

Psychiatric/physical symptoms. Psychiatric symptoms of “robo” intoxication include euphoria, altered time perception, disorientation, and tactile, visual and auditory hallucinations.⁷ Physical symptoms include excitation, nystagmus, tachycardia, hypertension, hyperthermia, vomiting, urinary retention, drowsiness, and rash. Extreme dextromethorphan withdrawal can cause dysphoria, insomnia, vomiting, diaphoresis, abdominal pain, and diarrhea.⁷

Psychiatric symptoms of intoxication with dextromethorphan or phencyclidine are similar, but phencyclidine-intoxicated patients typically present with fluctuating behavior and motor symptoms including tremor, dystonic reactions, and catalepsy.

Also watch for dermatitis on the forehead, nose, or cheeks, which can result from chronic abuse of preparations containing dextromethorphan plus bromide or chlorpheniramine.

Patient history. Has the patient abused dextromethorphan before? If so, how often? When was he last treated for decompensation after cold medication abuse?

Also check for abuse of other substances, and ask teenage patients if their friends use cold preparations recreationally.

Collateral information. Ask family members to search the patient’s room for supplies of cold medicine and for empty boxes and capsule cards, check the medicine chest regularly to see if cold medications are missing, and check the patient’s jacket or coat pockets for cold tablets or cough syrup.

Treating ‘robo’ abuse

Convincing the patient and family that dextromethorphan abuse can cause severe harm is critical to promoting a positive outcome. Referral to a substance abuse rehabilitation program or 12-step group can help.

Related resources

• U.S. Department of Justice, National Drug Intelligence Center. Intelligence bulletin: DXM (dextromethorphan). www.usdoj.gov/ndic/pubs11/11563/index.htm.
  
• Partnership for a Drug-Free America. Resource for parents. www.drugfree.org/Parent. Click on “Cough Medicine Abuse” under “Special Drug Reports.”
  
• U.S. Food and Drug Administraton. FDA warns against abuse of dextromethorphan (DXM). www.fda.gov, enter “dextromethorphan” in search field.
  

Drug brand names

• Risperidone • Risperdal
  

Disclosure

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

CASE: The man from Betelgeuse

Mr. F, age 33, has been hospitalized repeatedly for psychotic episodes after abuse of dextromethorphan in cold medications.

Approximately 1 week before presenting to us, Mr. F stormed out of his house after his father, with whom he lived, confronted him about spending his allowance on cold medications. He spent the week living on the streets, abusing dextromethorphan whenever he could get it.

One night, Mr. F approached a police officer at an accident scene and exclaimed, “Dude, I’m from the planet Betelgeuse.” He appeared disorganized as police questioned him, and officers transported him to the county hospital’s psychiatric emergency service.

At presentation, Mr. F is at times silly, irritable, and sleepy, and chants incantations during the intake interview. Alternately, he hears Jesus Christ and aliens from Betelgeuse telling him “everything is going to be cool” and voices of aliens threatening to abduct him.

We admit Mr. F to the inpatient psychiatric unit, start risperidone at 2 mg nightly, and titrate it to 6 mg nightly over 3 days, after which he is significantly more organized with reduced auditory hallucinations. At discharge 6 days later, he still occasionally hears Jesus but has partial insight into his obsession with aliens and no paranoid delusions. We continue risperidone, 6 mg nightly, and refer him to an outpatient mental health program. He visits the clinic once but avoids the attending psychiatrist.

Five days later, Mr. F begins hallucinating at home and his father brings him back to the emergency psychiatry unit. At presentation, the patient claims to be an agent of Satan and waves his arms wildly while performing “black magic.” He believes he is damned and that previous messages he thought came from Jesus and extraterrestrials were instead from the devil.

Mr. F’s father reports that over the weekend his son ingested 6 boxes of cold medicine—each with 16 tablets containing 30 mg of dextromethorphan. Peeling skin on the lower part of Mr. F’s forehead, the bridge of his nose, and under his eyes suggests chronic cold tablet abuse. We re-admit the patient after extended urine drug screen shows traces of chlorpheniramine.

The authors’ observations

Routine urine drug screens based on radio-immunoassay detect many substances, but an extended or comprehensive urine drug screen based on gas chromatography-mass spectrometry is needed to detect dextromethorphan.¹ Tertiary hospitals and reference laboratories usually offer these tests.

An extended urine screen will not detect dextromethorphan 24 hours after use because the agent has a 3- to 11-hour half-life. The test can, however, detect other active cold preparation compounds with longer half-lives, such as chlorpheniramine.

If extended urine screening is not available, clinical findings discussed later in this article can confirm recent cold medication abuse. Blood testing can reveal dextromethorphan levels, but a 3- to 6-mL sample may be needed.

HISTORY: ‘Sick’ at 16

Mr. F began abusing dextromethorphan at age 16, when friends would “turn him on” to 8-ounce bottles of cough syrup every other week. He later tried marijuana, cocaine, phencyclidine, methamphetamine, morphine, and LSD. Soon after graduating from high school, he stopped using substances and remained clean for several years.

At age 25, Mr. F suffered his first psychotic break, after which a psychiatrist diagnosed schizophrenia. Initial symptom control with antipsychotics helped him finish college.

Mr. F worked as a restaurant manager for about 4 months but found the job stressful and constantly argued with staff. He resumed abusing cough syrup to relieve his stress but soon became hooked on its dissociative and hallucinogenic effects. One night he ingested enough cough syrup to remain “high” until the next morning. He was hallucinating when he reported to work that day and was fired.

Since then, Mr. F’s cold medication abuse has escalated from biweekly to almost daily at presentation. He switched to tablets because the syrup induced cold symptoms and he finds the “buzz” from the tablets easier to control.

He typically dresses in black (in keeping with his satanic obsessions) and wears a long black overcoat with several pockets, that allows him to carry boxes of cold capsules, books, and other items.

Mr. F’s father has repeatedly tried to stop his son’s cold tablet abuse by cutting off his allowance. Dextromethorphan-containing cold medications are inexpensive, however—a box of 16 30-mg tablets costs as little as $1.50. Also, Mr. F often would get money for cold capsules by going to malls and participating in market research surveys.

 

In the past year, Mr. F was hospitalized 6 times after dextromethorphan-induced psychotic decompensations. He has been unemployed for more than 5 years, has not been in a serious romantic relationship since college, and depends on his father for financial support. He is not abusing other substances.

The authors’ observations

As many as 80% of patients with schizophrenia also have a substance abuse disorder.² Access to psychoactive substances, kindling associated with schizophrenia, and attempts to stop hallucinations with alcohol or illicit drugs may explain this high prevalence.² Also, genetic or phenotypic vulnerability in schizophrenia might alter the mesolimbic dopamine system that moderates reward.

Compared with patients with schizophrenia who are substance-free, comorbid substance abuse in schizophrenia increases:

• severity of psychotic symptoms
  
• likelihood of emergency service use
  
• risk of suicide, illness, injury, hospitalization, or incarceration.³
  

Box 1

Whereas alcohol, marijuana, and cocaine abuse are common in schizophrenia,² to our knowledge only 2 other cases of comorbid dextromethorphan dependence and schizophrenia have been reported.^4,5

Mr. F responded well to risperidone when he wasn’t abusing cold tablets. After his last hospitalization, we referred him to a comprehensive outpatient program that could have addressed his cold medicine abuse and reintegrated him into the workplace. He avoided seeing the clinic psychiatrist, however, after promising his case manager that he would stop abusing dextromethorphan.

TREATMENT: Back to Betelgeuse

Upon re-admission, we restart risperidone, 6 mg nightly. Mr. F shows extreme somnolence caused by massive cold capsule use and is minimally cooperative with the psychiatrist’s follow-up interview. Over 36 hours, he awakens only for meals and medication and to use the bathroom. Once the somnolence passes, he cannot fall asleep at night.

Six days after admission, Mr. F is organized and hears voices mostly from Jesus with some demonic delusions. Extended urine drug screen taken 3 days after admission shows traces of chlorpheniramine but no dextromethorphan.

By day 7, Mr. F is nearly free of delusions and is discharged the next day. We continue risperidone, 6 mg nightly, to prevent the “voices,” and add diphenhydramine, 50 mg nightly, to regulate his sleep. We arrange follow-up care at an outpatient clinic, but Mr. F again avoids the clinic psychiatrist.

The authors’ observations

Mr. F’s “robo” binge triggered a profound and prolonged psychotic decompensation.

Dextrorphan—a pharmacologically active metabolite of dextromethorphan— might have disrupted cortical and sub-cortical glutamatergic neurotransmission,⁶ leading to florid psychosis and delayed recovery. Induction of the cytochrome P-450 2D6 isoenzyme, which metabolizes dextromethorphan, also could have prolonged Mr. F’s psychosis (Box 1).^7-11

RELAPSE: Return visits

Three weeks after discharge, Mr. F fights with police officers after they find him hallucinating in the streets. Police charge him with disorderly conduct and resisting arrest and bring him back to the psychiatric ER. We again resolve his auditory hallucinations with risperidone, 6 mg nightly. After 8 days we discharge him to police, who then transport him to jail and later release him on bail.

Six months later, Mr. F is hospitalized twice in 2 months after dextromethorphan-induced decompensations. He recovers quickly both times but lacks insight into his mental illness and his “robo” problem.

The authors’ observations

Dextromethorphan, known by many street names (Box 2), is contained in more than 100 OTC preparations, and is sold on the Internet in powder form.

Abuse of dextromethorphan-containing preparations is rising among teenagers and young adults. Nonmedical “robo” use led to 5,581 ER visits in the United States in 2004,¹² and California reported a 10-fold rise in dextromethorphan abuse among teenagers from 1999 to 2004.

 

¹³ Numerous factors explain this increase:

• Most people do not know that dextromethorphan-laced medications are dangerous if misused.
  
• These preparations can be purchased at many stores or snatched from the medicine chest.
  
• Several Web sites describe how to “safely” abuse dextromethorphan.¹³
  

Further, some pediatricians, family physicians, emergency physicians, and psychiatrists do not suspect “robo” abuse, in part because ordinary urine drug screens do not detect dextromethorphan.

medical consequences

Many dextromethorphan-laced preparations contain other active compounds—such as pseudoephedrine, acetaminophen, chlorpheniramine, guaifenesin, or bromide—that can cause serious adverse effects at above-normal doses. Abuse of medications containing both chlorpheniramine and dextromethorphan leads to hallucinogenic euphoria and dissociation, followed by hours of intense somnolence.

Dextromethorphan can cause serotonin syndrome when taken with serotonergic drugs such as amphetamines, cocaine, monoamine oxidase inhibitors, or selective serotonin reuptake inhibitors. Symptoms include tachycardia, hypertension, diaphoresis, mydriasis, myoclonus, agitation, and seizures.

Box 2

The authors’ observations

Physical and psychiatric symptoms, patient history, and collateral information together can confirm dextromethorphan abuse in patients who present with mainly visual and tactile hallucinations. The signs are easy to miss in patients with schizophrenia because schizophrenia is believed to be causing the psychosis.

Psychiatric/physical symptoms. Psychiatric symptoms of “robo” intoxication include euphoria, altered time perception, disorientation, and tactile, visual and auditory hallucinations.⁷ Physical symptoms include excitation, nystagmus, tachycardia, hypertension, hyperthermia, vomiting, urinary retention, drowsiness, and rash. Extreme dextromethorphan withdrawal can cause dysphoria, insomnia, vomiting, diaphoresis, abdominal pain, and diarrhea.⁷

Psychiatric symptoms of intoxication with dextromethorphan or phencyclidine are similar, but phencyclidine-intoxicated patients typically present with fluctuating behavior and motor symptoms including tremor, dystonic reactions, and catalepsy.

Also watch for dermatitis on the forehead, nose, or cheeks, which can result from chronic abuse of preparations containing dextromethorphan plus bromide or chlorpheniramine.

Patient history. Has the patient abused dextromethorphan before? If so, how often? When was he last treated for decompensation after cold medication abuse?

Also check for abuse of other substances, and ask teenage patients if their friends use cold preparations recreationally.

Collateral information. Ask family members to search the patient’s room for supplies of cold medicine and for empty boxes and capsule cards, check the medicine chest regularly to see if cold medications are missing, and check the patient’s jacket or coat pockets for cold tablets or cough syrup.

Treating ‘robo’ abuse

Convincing the patient and family that dextromethorphan abuse can cause severe harm is critical to promoting a positive outcome. Referral to a substance abuse rehabilitation program or 12-step group can help.

Related resources

• U.S. Department of Justice, National Drug Intelligence Center. Intelligence bulletin: DXM (dextromethorphan). www.usdoj.gov/ndic/pubs11/11563/index.htm.
  
• Partnership for a Drug-Free America. Resource for parents. www.drugfree.org/Parent. Click on “Cough Medicine Abuse” under “Special Drug Reports.”
  
• U.S. Food and Drug Administraton. FDA warns against abuse of dextromethorphan (DXM). www.fda.gov, enter “dextromethorphan” in search field.
  

Drug brand names

• Risperidone • Risperdal
  

Disclosure

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

HISTORY: ‘Unusual behavior’

Ms. L, age 44, has severe cerebral palsy and has used a wheelchair since childhood. Her mother, who had been her primary caretaker, died 12 years ago, and her stepsister has been caring for her since.

Ms. L’s primary care physician reports that the patient has been “acting out” lately and asks us to evaluate her “unusual behavior.” Six months ago, the physician prescribed escitalopram, 30 mg/d, to treat depressive symptoms stemming from her chronic neurologic disorder.

We interview Ms. L and her stepsister together. The patient says she has been depressed, irritable, and moody, and her stepsister confirms this. The patient shows no signs of distress during the interview, and her answers appear short and guarded.

The stepsister says she typically spends her day turning Ms. L to prevent bedsores, feeding and bathing her, replacing her urinary catheter and emptying her urinary bag, and helping her to the bathroom. At day’s end, the stepsister has little time to spend with her husband or for other activities. She says at times she resents tending to Ms. L’s constant needs and feels “stressed out.”

We diagnose Ms. L with a mood disorder caused by a general medical condition. We continue escitalopram, 30 mg/d, and add oxcarbazepine, 150 mg bid, to treat her irritability and lability.

FOLLOW-UP: ‘She’s abusing me’

At Ms. L’s follow-up visit 2 weeks later, we ask her stepsister to leave the examination room and interview the patient alone to gauge her emotional condition and insight.

Seconds later, Ms. L starts crying hysterically, then reports that for 12 years her stepsister has been beating her, usually after she requests something. Yesterday, she says, her stepsister started punching her after she asked to be taken to the park.

Ms. L says the abuse is escalating and now occurs daily. She says she is covered with bruises from the last beating, although no bruises are visible at first glance. Afraid to go home with her stepsister, she pleads for help.

At this point, I would:

1. call the primary care physician for collateral information
   
2. examine Ms. L for bruises
   
3. get the stepsister’s side of the story
   
4. contact state protective services
   
5. all of the above
   

The authors’ observations

Is Ms. L being physically abused, or is a psychiatric condition driving her to fabricate these allegations?

We saw nothing suspicious during the first interview with the stepsister, although she acknowledged difficulty coping with Ms. L’s constant requests (Box 1).¹ Caring for a severely disabled person day in and day out can be trying for both the caregiver and her family, and the stepsister could be taking her frustrations out on Ms. L.

Until proven otherwise, we must assume Ms. L is being harmed and seek more information. We also must watch for signs of a delusional or factitious disorder or malingering—any of which would suggest the allegations are false.

Box 1

HISTORY: A second opinion

We ask Ms. L if we can discuss the allegations with her and her stepsister, but she fears retaliation and insists that we not speak to the caretaker.

We then call Ms. L’s primary care physician, who has been managing her care for several years. He says the patient has begged him numerous times for protection from her stepsister, but adds he has found no evidence of abuse. He notes that he has witnessed tension between the 2 women during office visits and cannot dismiss the possibility of abuse.

The attending psychiatrist performs a brief physical exam with the resident looking on but finds no bruises, excoriations, or unusual scarring on her arms and legs. Because our outpatient clinic lacks an examination room, we do not perform a whole-body exam.

We then notify state protective services. There, an agent tells us that in the past year, Ms. L has made 4 allegations of caretaker abuse, none of which were substantiated after extensive investigation. The agent says her office will assign a case worker but considers the case a low priority.

 

When we inform Ms. L of our findings, she frantically insists that her caretaker is beating her once a week and that the abuse has gone undetected. We become skeptical, recalling that Ms. L earlier said the beatings were daily.

Ms. L says she is afraid to go home and wonders where she can stay. Having no friends or other family members nearby, she requests hospitalization.

At this point, I would:

1. discharge Ms. L to a safe house with close follow-up
   
2. hospitalize her for safety and diagnostic clarification
   
3. discharge her to her stepsister with close follow-up
   

The authors’ observations

Ms. L’s allegations pose a medical, ethical, and legal challenge. Physical examination and input from a protective services officer suggest Ms. L is fabricating the allegations. On the other hand, if the accusations are true, sending Ms. L home with her stepsister would endanger her.

We could hospitalize the patient and substantiate the allegations later, but we cannot justify taxing limited hospital resources when the need is questionable. We cannot send her to a safe house because of her severe physical disability, nor can we discuss the allegations with her stepsister because Ms. L instructed us not to.

Box 2

DISPOSITION: Going home

After meeting with hospital officials and clinic staff, we decide that Ms. L does not meet admission criteria. We discharge her to her stepsister and see the patient again the next day.

The authors’ observations

Legal duty. Our legal duty to protect a suspected abuse victim depends on the jurisdiction in which treatment is delivered.

Texas law, for example, requires health care providers to report suspected abuse of a “vulnerable adult.”² Failure to do so is considered a misdemeanor. If the report is made in good faith, the physician is immune from civil and criminal liability, even if the allegations are proven false.²

Many states do not require physicians to report suspected abuse, but this complicates the decision process. If the suspicion is correct, not reporting it might constitute malpractice or negligence and could provoke future lawsuits or complaints to the state medical board. Worse, the abuse may escalate and cause irreparable harm to the patient. Conversely, reporting unfounded suspicions of abuse can destroy the doctor-patient relationship, prompt the caregiver to retaliate against the patient, or inspire patients or caregivers to sue the physician.

If you suspect patient abuse and your state mandates reporting, contact the state protective services agency at once (seeRelated Resources,). Base your report on a thorough history and physical, psychiatric evaluation, and—when available—collateral information.

If your state does not mandate reporting, obtain the patient’s consent to file a complaint with state protective services. By providing informed consent, the patient gives permission to disclose protected health information, and confidentiality is not breached.

Be careful when obtaining informed consent, especially when the patient is ambivalent about reporting because of:

• fear of retaliation from the abuser
  
• fear of the social stigma associated with abuse
  
• or the patient’s false belief that she deserves the abuse.
  

The level of suspicion needed to justify reporting suspected abuse cannot be quantified and depends on the allegation’s severity and your clinical judgment. Also, what constitutes a “vulnerable adult” varies from state to state. Knowing your state’s laws and consulting with legal counsel are critical in difficult cases.

Ethical responsibility. Even if our legal responsibility is minimal, we should go further to do what is best for the patient.

Texas, for example, does not require physicians to hospitalize or find a safe environment for a suspected abuse victim.² But if you see evidence of abuse, notify authorities and offer the patient information about local safe houses, support groups, and social services—even if not mandated by law. If resources are available, consider hospitalizing the patient and work with his or her social worker, therapist, or clergy to orchestrate outpatient services.

While treating a suspected abuse victim, consider consulting the caretaker if the patient agrees to the caretaker’s involvement. Caretakers can help you gather collateral information, plan treatment, and assist with psychoeducation. Also steer “stressed-out” caretakers toward a support group or online resource (Box 2).

Whether or not abuse has occurred, empathizing with the caretaker about the difficulty of caring for the patient could diminish the caretaker’s stress and reduce the risk of abuse.

 

FOLLOW-UP: Truth or delusion?

At her appointment the next day, Ms. L says things are fine at home and does not bring up the abuse allegations. We then see her every 3 days for 2 weeks, weekly for 4 weeks, and every 3 weeks thereafter as the apparent risk of abuse diminishes. At each visit, she says her caretaker is not beating her but occasionally complains that she is verbally abusive.

Three weeks after her first follow-up, Ms. L enters the examination room agitated and frightened; she says another patient in the waiting room has just tried to strangle her for no apparent reason. Upon questioning, office staff say they saw no attack and note that the accused patient is a feeble woman with no history of violence; we doubt she assaulted Ms. L.

Ms. L suffers from:

1. repeated physical abuse
   
2. delusional disorder
   
3. factitious disorder
   
4. malingering
   

The authors’ observations

Although Ms. L clearly was not assaulted in the waiting room, this complaint is key to understanding her case. Although whether she is being abused at home remains unclear, evidence increasingly suggests that she suffers from delusions.

Delusions are beliefs that are fixed, false, and not ordinarily accepted by others in a patient’s culture or subculture.³ Delusional disorder is characterized by nonbizarre delusions lasting >1 month (>3 months according to ICD-10 criteria)⁴ with relatively preserved functioning and without prominent hallucinations. DSM-IV-TR defines bizarre delusions as “clearly implausible, not understandable, and not derived from ordinary life experience.”^4,5

Ms. L most likely has a paranoid or persecutory type delusional disorder in which she is convinced she is being harmed. Her delusional thoughts might yield mood symptoms such as anger and irritability, and she might become assaultive. Often, such patients are extraordinarily determined to succeed against “the conspirators” and frequently appeal to the legal system or law enforcement.³

Differentiating between a patient’s delusions and reality can be difficult, leading clinicians to seek collateral information from family, past medical records, or providers to establish a diagnosis. The delusions might become less circumscribed over time, or additional information might clear the clinical picture.

Ms. L’s psychological makeup might help us rule out other diagnoses. Her request for hospitalization, for example, could suggest factitious illness, but she is disabled enough to play the sick role without manufacturing symptoms. Also, she seeks hospitalization because she has no family or friends to turn to. We rule out malingering because Ms. L has nothing to gain by accusing a stranger of choking her in the waiting room.

Treating delusional disorder

Pharmacotherapy and psychotherapy typically are used together to treat delusional disorder.

Pharmacotherapy. Antipsychotics such as olanzapine, 5 to 10 mg nightly, or risperidone, 1 to 2 mg nightly, can decrease the delusional thoughts’ intensity and frequency, allowing patients to function more appropriately.³ If 2 or more antipsychotic trials do not control delusional thoughts, consider starting clozapine at 300 mg/d and titrating to 900 mg/d.

Add an antidepressant if delusional thinking causes depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, 10 to 20 mg/d, or fluoxetine, 20 to 40 mg/d, are a good starting point. Consider other antidepressant types if SSRIs do not work.

Adjunctive benzodiazepines such as clonazepam, 1 to 2 mg/d, or lorazepam, 1 to 2 mg bid as needed, can help manage acute anxiety or agitation stemming from delusions.

Psychotherapy. Supportive therapy can alleviate anxiety and depression that often result from delusional thinking. Cognitive-behavioral therapy can teach patients to stop acting on their delusions.

Once rapport is established, consider challenging delusional beliefs by having the patient list evidence supporting or refuting the delusions. Be careful not to confront delusional thinking too quickly or aggressively, as this approach often does not change the patient’s beliefs and weakens the therapeutic alliance.³

TREATMENT: Fewer complaints

We still see Ms. L every 3 weeks for supportive psychotherapy and medication management. We continue oxcarbazepine, 150 mg bid, and escitalopram, 30 mg/d, and add risperidone, 1 mg at bedtime, to target her delusional thinking, lability, and irritability.

Over 6 months, Ms. L’s complaints of abuse become less emphatic. She endorses the abuse less frequently—every 3 to 4 visits—and only if the clinician specifically asks about it. Most often, she denies abuse is occurring but says it happened previously. At each visit, we document her statements and explain in her chart why we have not notified adult protective services or police.

Related resources

• National Adult Protective Services Association. Links to adult protection agencies nationwide. www.apsnetwork.org.
  
• National Center on Elder Abuse. www.elderabusecenter.org.
  

 

Drug brand names

• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Oxcarbazepine • Trileptal
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  

Disclosure

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

HISTORY: ‘Unusual behavior’

Ms. L, age 44, has severe cerebral palsy and has used a wheelchair since childhood. Her mother, who had been her primary caretaker, died 12 years ago, and her stepsister has been caring for her since.

Ms. L’s primary care physician reports that the patient has been “acting out” lately and asks us to evaluate her “unusual behavior.” Six months ago, the physician prescribed escitalopram, 30 mg/d, to treat depressive symptoms stemming from her chronic neurologic disorder.

We interview Ms. L and her stepsister together. The patient says she has been depressed, irritable, and moody, and her stepsister confirms this. The patient shows no signs of distress during the interview, and her answers appear short and guarded.

The stepsister says she typically spends her day turning Ms. L to prevent bedsores, feeding and bathing her, replacing her urinary catheter and emptying her urinary bag, and helping her to the bathroom. At day’s end, the stepsister has little time to spend with her husband or for other activities. She says at times she resents tending to Ms. L’s constant needs and feels “stressed out.”

We diagnose Ms. L with a mood disorder caused by a general medical condition. We continue escitalopram, 30 mg/d, and add oxcarbazepine, 150 mg bid, to treat her irritability and lability.

FOLLOW-UP: ‘She’s abusing me’

At Ms. L’s follow-up visit 2 weeks later, we ask her stepsister to leave the examination room and interview the patient alone to gauge her emotional condition and insight.

Seconds later, Ms. L starts crying hysterically, then reports that for 12 years her stepsister has been beating her, usually after she requests something. Yesterday, she says, her stepsister started punching her after she asked to be taken to the park.

Ms. L says the abuse is escalating and now occurs daily. She says she is covered with bruises from the last beating, although no bruises are visible at first glance. Afraid to go home with her stepsister, she pleads for help.

At this point, I would:

1. call the primary care physician for collateral information
   
2. examine Ms. L for bruises
   
3. get the stepsister’s side of the story
   
4. contact state protective services
   
5. all of the above
   

The authors’ observations

Is Ms. L being physically abused, or is a psychiatric condition driving her to fabricate these allegations?

We saw nothing suspicious during the first interview with the stepsister, although she acknowledged difficulty coping with Ms. L’s constant requests (Box 1).¹ Caring for a severely disabled person day in and day out can be trying for both the caregiver and her family, and the stepsister could be taking her frustrations out on Ms. L.

Until proven otherwise, we must assume Ms. L is being harmed and seek more information. We also must watch for signs of a delusional or factitious disorder or malingering—any of which would suggest the allegations are false.

Box 1

HISTORY: A second opinion

We ask Ms. L if we can discuss the allegations with her and her stepsister, but she fears retaliation and insists that we not speak to the caretaker.

We then call Ms. L’s primary care physician, who has been managing her care for several years. He says the patient has begged him numerous times for protection from her stepsister, but adds he has found no evidence of abuse. He notes that he has witnessed tension between the 2 women during office visits and cannot dismiss the possibility of abuse.

The attending psychiatrist performs a brief physical exam with the resident looking on but finds no bruises, excoriations, or unusual scarring on her arms and legs. Because our outpatient clinic lacks an examination room, we do not perform a whole-body exam.

We then notify state protective services. There, an agent tells us that in the past year, Ms. L has made 4 allegations of caretaker abuse, none of which were substantiated after extensive investigation. The agent says her office will assign a case worker but considers the case a low priority.

 

When we inform Ms. L of our findings, she frantically insists that her caretaker is beating her once a week and that the abuse has gone undetected. We become skeptical, recalling that Ms. L earlier said the beatings were daily.

Ms. L says she is afraid to go home and wonders where she can stay. Having no friends or other family members nearby, she requests hospitalization.

At this point, I would:

1. discharge Ms. L to a safe house with close follow-up
   
2. hospitalize her for safety and diagnostic clarification
   
3. discharge her to her stepsister with close follow-up
   

The authors’ observations

Ms. L’s allegations pose a medical, ethical, and legal challenge. Physical examination and input from a protective services officer suggest Ms. L is fabricating the allegations. On the other hand, if the accusations are true, sending Ms. L home with her stepsister would endanger her.

We could hospitalize the patient and substantiate the allegations later, but we cannot justify taxing limited hospital resources when the need is questionable. We cannot send her to a safe house because of her severe physical disability, nor can we discuss the allegations with her stepsister because Ms. L instructed us not to.

Box 2

DISPOSITION: Going home

After meeting with hospital officials and clinic staff, we decide that Ms. L does not meet admission criteria. We discharge her to her stepsister and see the patient again the next day.

The authors’ observations

Legal duty. Our legal duty to protect a suspected abuse victim depends on the jurisdiction in which treatment is delivered.

Texas law, for example, requires health care providers to report suspected abuse of a “vulnerable adult.”² Failure to do so is considered a misdemeanor. If the report is made in good faith, the physician is immune from civil and criminal liability, even if the allegations are proven false.²

Many states do not require physicians to report suspected abuse, but this complicates the decision process. If the suspicion is correct, not reporting it might constitute malpractice or negligence and could provoke future lawsuits or complaints to the state medical board. Worse, the abuse may escalate and cause irreparable harm to the patient. Conversely, reporting unfounded suspicions of abuse can destroy the doctor-patient relationship, prompt the caregiver to retaliate against the patient, or inspire patients or caregivers to sue the physician.

If you suspect patient abuse and your state mandates reporting, contact the state protective services agency at once (seeRelated Resources,). Base your report on a thorough history and physical, psychiatric evaluation, and—when available—collateral information.

If your state does not mandate reporting, obtain the patient’s consent to file a complaint with state protective services. By providing informed consent, the patient gives permission to disclose protected health information, and confidentiality is not breached.

Be careful when obtaining informed consent, especially when the patient is ambivalent about reporting because of:

• fear of retaliation from the abuser
  
• fear of the social stigma associated with abuse
  
• or the patient’s false belief that she deserves the abuse.
  

The level of suspicion needed to justify reporting suspected abuse cannot be quantified and depends on the allegation’s severity and your clinical judgment. Also, what constitutes a “vulnerable adult” varies from state to state. Knowing your state’s laws and consulting with legal counsel are critical in difficult cases.

Ethical responsibility. Even if our legal responsibility is minimal, we should go further to do what is best for the patient.

Texas, for example, does not require physicians to hospitalize or find a safe environment for a suspected abuse victim.² But if you see evidence of abuse, notify authorities and offer the patient information about local safe houses, support groups, and social services—even if not mandated by law. If resources are available, consider hospitalizing the patient and work with his or her social worker, therapist, or clergy to orchestrate outpatient services.

While treating a suspected abuse victim, consider consulting the caretaker if the patient agrees to the caretaker’s involvement. Caretakers can help you gather collateral information, plan treatment, and assist with psychoeducation. Also steer “stressed-out” caretakers toward a support group or online resource (Box 2).

Whether or not abuse has occurred, empathizing with the caretaker about the difficulty of caring for the patient could diminish the caretaker’s stress and reduce the risk of abuse.

 

FOLLOW-UP: Truth or delusion?

At her appointment the next day, Ms. L says things are fine at home and does not bring up the abuse allegations. We then see her every 3 days for 2 weeks, weekly for 4 weeks, and every 3 weeks thereafter as the apparent risk of abuse diminishes. At each visit, she says her caretaker is not beating her but occasionally complains that she is verbally abusive.

Three weeks after her first follow-up, Ms. L enters the examination room agitated and frightened; she says another patient in the waiting room has just tried to strangle her for no apparent reason. Upon questioning, office staff say they saw no attack and note that the accused patient is a feeble woman with no history of violence; we doubt she assaulted Ms. L.

Ms. L suffers from:

1. repeated physical abuse
   
2. delusional disorder
   
3. factitious disorder
   
4. malingering
   

The authors’ observations

Although Ms. L clearly was not assaulted in the waiting room, this complaint is key to understanding her case. Although whether she is being abused at home remains unclear, evidence increasingly suggests that she suffers from delusions.

Delusions are beliefs that are fixed, false, and not ordinarily accepted by others in a patient’s culture or subculture.³ Delusional disorder is characterized by nonbizarre delusions lasting >1 month (>3 months according to ICD-10 criteria)⁴ with relatively preserved functioning and without prominent hallucinations. DSM-IV-TR defines bizarre delusions as “clearly implausible, not understandable, and not derived from ordinary life experience.”^4,5

Ms. L most likely has a paranoid or persecutory type delusional disorder in which she is convinced she is being harmed. Her delusional thoughts might yield mood symptoms such as anger and irritability, and she might become assaultive. Often, such patients are extraordinarily determined to succeed against “the conspirators” and frequently appeal to the legal system or law enforcement.³

Differentiating between a patient’s delusions and reality can be difficult, leading clinicians to seek collateral information from family, past medical records, or providers to establish a diagnosis. The delusions might become less circumscribed over time, or additional information might clear the clinical picture.

Ms. L’s psychological makeup might help us rule out other diagnoses. Her request for hospitalization, for example, could suggest factitious illness, but she is disabled enough to play the sick role without manufacturing symptoms. Also, she seeks hospitalization because she has no family or friends to turn to. We rule out malingering because Ms. L has nothing to gain by accusing a stranger of choking her in the waiting room.

Treating delusional disorder

Pharmacotherapy and psychotherapy typically are used together to treat delusional disorder.

Pharmacotherapy. Antipsychotics such as olanzapine, 5 to 10 mg nightly, or risperidone, 1 to 2 mg nightly, can decrease the delusional thoughts’ intensity and frequency, allowing patients to function more appropriately.³ If 2 or more antipsychotic trials do not control delusional thoughts, consider starting clozapine at 300 mg/d and titrating to 900 mg/d.

Add an antidepressant if delusional thinking causes depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, 10 to 20 mg/d, or fluoxetine, 20 to 40 mg/d, are a good starting point. Consider other antidepressant types if SSRIs do not work.

Adjunctive benzodiazepines such as clonazepam, 1 to 2 mg/d, or lorazepam, 1 to 2 mg bid as needed, can help manage acute anxiety or agitation stemming from delusions.

Psychotherapy. Supportive therapy can alleviate anxiety and depression that often result from delusional thinking. Cognitive-behavioral therapy can teach patients to stop acting on their delusions.

Once rapport is established, consider challenging delusional beliefs by having the patient list evidence supporting or refuting the delusions. Be careful not to confront delusional thinking too quickly or aggressively, as this approach often does not change the patient’s beliefs and weakens the therapeutic alliance.³

TREATMENT: Fewer complaints

We still see Ms. L every 3 weeks for supportive psychotherapy and medication management. We continue oxcarbazepine, 150 mg bid, and escitalopram, 30 mg/d, and add risperidone, 1 mg at bedtime, to target her delusional thinking, lability, and irritability.

Over 6 months, Ms. L’s complaints of abuse become less emphatic. She endorses the abuse less frequently—every 3 to 4 visits—and only if the clinician specifically asks about it. Most often, she denies abuse is occurring but says it happened previously. At each visit, we document her statements and explain in her chart why we have not notified adult protective services or police.

Related resources

• National Adult Protective Services Association. Links to adult protection agencies nationwide. www.apsnetwork.org.
  
• National Center on Elder Abuse. www.elderabusecenter.org.
  

 

Drug brand names

• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Oxcarbazepine • Trileptal
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  

Disclosure

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

HISTORY: ‘Unusual behavior’

Ms. L, age 44, has severe cerebral palsy and has used a wheelchair since childhood. Her mother, who had been her primary caretaker, died 12 years ago, and her stepsister has been caring for her since.

Ms. L’s primary care physician reports that the patient has been “acting out” lately and asks us to evaluate her “unusual behavior.” Six months ago, the physician prescribed escitalopram, 30 mg/d, to treat depressive symptoms stemming from her chronic neurologic disorder.

We interview Ms. L and her stepsister together. The patient says she has been depressed, irritable, and moody, and her stepsister confirms this. The patient shows no signs of distress during the interview, and her answers appear short and guarded.

The stepsister says she typically spends her day turning Ms. L to prevent bedsores, feeding and bathing her, replacing her urinary catheter and emptying her urinary bag, and helping her to the bathroom. At day’s end, the stepsister has little time to spend with her husband or for other activities. She says at times she resents tending to Ms. L’s constant needs and feels “stressed out.”

We diagnose Ms. L with a mood disorder caused by a general medical condition. We continue escitalopram, 30 mg/d, and add oxcarbazepine, 150 mg bid, to treat her irritability and lability.

FOLLOW-UP: ‘She’s abusing me’

At Ms. L’s follow-up visit 2 weeks later, we ask her stepsister to leave the examination room and interview the patient alone to gauge her emotional condition and insight.

Seconds later, Ms. L starts crying hysterically, then reports that for 12 years her stepsister has been beating her, usually after she requests something. Yesterday, she says, her stepsister started punching her after she asked to be taken to the park.

Ms. L says the abuse is escalating and now occurs daily. She says she is covered with bruises from the last beating, although no bruises are visible at first glance. Afraid to go home with her stepsister, she pleads for help.

At this point, I would:

1. call the primary care physician for collateral information
   
2. examine Ms. L for bruises
   
3. get the stepsister’s side of the story
   
4. contact state protective services
   
5. all of the above
   

The authors’ observations

Is Ms. L being physically abused, or is a psychiatric condition driving her to fabricate these allegations?

We saw nothing suspicious during the first interview with the stepsister, although she acknowledged difficulty coping with Ms. L’s constant requests (Box 1).¹ Caring for a severely disabled person day in and day out can be trying for both the caregiver and her family, and the stepsister could be taking her frustrations out on Ms. L.

Until proven otherwise, we must assume Ms. L is being harmed and seek more information. We also must watch for signs of a delusional or factitious disorder or malingering—any of which would suggest the allegations are false.

Box 1

HISTORY: A second opinion

We ask Ms. L if we can discuss the allegations with her and her stepsister, but she fears retaliation and insists that we not speak to the caretaker.

We then call Ms. L’s primary care physician, who has been managing her care for several years. He says the patient has begged him numerous times for protection from her stepsister, but adds he has found no evidence of abuse. He notes that he has witnessed tension between the 2 women during office visits and cannot dismiss the possibility of abuse.

The attending psychiatrist performs a brief physical exam with the resident looking on but finds no bruises, excoriations, or unusual scarring on her arms and legs. Because our outpatient clinic lacks an examination room, we do not perform a whole-body exam.

We then notify state protective services. There, an agent tells us that in the past year, Ms. L has made 4 allegations of caretaker abuse, none of which were substantiated after extensive investigation. The agent says her office will assign a case worker but considers the case a low priority.

 

When we inform Ms. L of our findings, she frantically insists that her caretaker is beating her once a week and that the abuse has gone undetected. We become skeptical, recalling that Ms. L earlier said the beatings were daily.

Ms. L says she is afraid to go home and wonders where she can stay. Having no friends or other family members nearby, she requests hospitalization.

At this point, I would:

1. discharge Ms. L to a safe house with close follow-up
   
2. hospitalize her for safety and diagnostic clarification
   
3. discharge her to her stepsister with close follow-up
   

The authors’ observations

Ms. L’s allegations pose a medical, ethical, and legal challenge. Physical examination and input from a protective services officer suggest Ms. L is fabricating the allegations. On the other hand, if the accusations are true, sending Ms. L home with her stepsister would endanger her.

We could hospitalize the patient and substantiate the allegations later, but we cannot justify taxing limited hospital resources when the need is questionable. We cannot send her to a safe house because of her severe physical disability, nor can we discuss the allegations with her stepsister because Ms. L instructed us not to.

Box 2

DISPOSITION: Going home

After meeting with hospital officials and clinic staff, we decide that Ms. L does not meet admission criteria. We discharge her to her stepsister and see the patient again the next day.

The authors’ observations

Legal duty. Our legal duty to protect a suspected abuse victim depends on the jurisdiction in which treatment is delivered.

Texas law, for example, requires health care providers to report suspected abuse of a “vulnerable adult.”² Failure to do so is considered a misdemeanor. If the report is made in good faith, the physician is immune from civil and criminal liability, even if the allegations are proven false.²

Many states do not require physicians to report suspected abuse, but this complicates the decision process. If the suspicion is correct, not reporting it might constitute malpractice or negligence and could provoke future lawsuits or complaints to the state medical board. Worse, the abuse may escalate and cause irreparable harm to the patient. Conversely, reporting unfounded suspicions of abuse can destroy the doctor-patient relationship, prompt the caregiver to retaliate against the patient, or inspire patients or caregivers to sue the physician.

If you suspect patient abuse and your state mandates reporting, contact the state protective services agency at once (seeRelated Resources,). Base your report on a thorough history and physical, psychiatric evaluation, and—when available—collateral information.

If your state does not mandate reporting, obtain the patient’s consent to file a complaint with state protective services. By providing informed consent, the patient gives permission to disclose protected health information, and confidentiality is not breached.

Be careful when obtaining informed consent, especially when the patient is ambivalent about reporting because of:

• fear of retaliation from the abuser
  
• fear of the social stigma associated with abuse
  
• or the patient’s false belief that she deserves the abuse.
  

The level of suspicion needed to justify reporting suspected abuse cannot be quantified and depends on the allegation’s severity and your clinical judgment. Also, what constitutes a “vulnerable adult” varies from state to state. Knowing your state’s laws and consulting with legal counsel are critical in difficult cases.

Ethical responsibility. Even if our legal responsibility is minimal, we should go further to do what is best for the patient.

Texas, for example, does not require physicians to hospitalize or find a safe environment for a suspected abuse victim.² But if you see evidence of abuse, notify authorities and offer the patient information about local safe houses, support groups, and social services—even if not mandated by law. If resources are available, consider hospitalizing the patient and work with his or her social worker, therapist, or clergy to orchestrate outpatient services.

While treating a suspected abuse victim, consider consulting the caretaker if the patient agrees to the caretaker’s involvement. Caretakers can help you gather collateral information, plan treatment, and assist with psychoeducation. Also steer “stressed-out” caretakers toward a support group or online resource (Box 2).

Whether or not abuse has occurred, empathizing with the caretaker about the difficulty of caring for the patient could diminish the caretaker’s stress and reduce the risk of abuse.

 

FOLLOW-UP: Truth or delusion?

At her appointment the next day, Ms. L says things are fine at home and does not bring up the abuse allegations. We then see her every 3 days for 2 weeks, weekly for 4 weeks, and every 3 weeks thereafter as the apparent risk of abuse diminishes. At each visit, she says her caretaker is not beating her but occasionally complains that she is verbally abusive.

Three weeks after her first follow-up, Ms. L enters the examination room agitated and frightened; she says another patient in the waiting room has just tried to strangle her for no apparent reason. Upon questioning, office staff say they saw no attack and note that the accused patient is a feeble woman with no history of violence; we doubt she assaulted Ms. L.

Ms. L suffers from:

1. repeated physical abuse
   
2. delusional disorder
   
3. factitious disorder
   
4. malingering
   

The authors’ observations

Although Ms. L clearly was not assaulted in the waiting room, this complaint is key to understanding her case. Although whether she is being abused at home remains unclear, evidence increasingly suggests that she suffers from delusions.

Delusions are beliefs that are fixed, false, and not ordinarily accepted by others in a patient’s culture or subculture.³ Delusional disorder is characterized by nonbizarre delusions lasting >1 month (>3 months according to ICD-10 criteria)⁴ with relatively preserved functioning and without prominent hallucinations. DSM-IV-TR defines bizarre delusions as “clearly implausible, not understandable, and not derived from ordinary life experience.”^4,5

Ms. L most likely has a paranoid or persecutory type delusional disorder in which she is convinced she is being harmed. Her delusional thoughts might yield mood symptoms such as anger and irritability, and she might become assaultive. Often, such patients are extraordinarily determined to succeed against “the conspirators” and frequently appeal to the legal system or law enforcement.³

Differentiating between a patient’s delusions and reality can be difficult, leading clinicians to seek collateral information from family, past medical records, or providers to establish a diagnosis. The delusions might become less circumscribed over time, or additional information might clear the clinical picture.

Ms. L’s psychological makeup might help us rule out other diagnoses. Her request for hospitalization, for example, could suggest factitious illness, but she is disabled enough to play the sick role without manufacturing symptoms. Also, she seeks hospitalization because she has no family or friends to turn to. We rule out malingering because Ms. L has nothing to gain by accusing a stranger of choking her in the waiting room.

Treating delusional disorder

Pharmacotherapy and psychotherapy typically are used together to treat delusional disorder.

Pharmacotherapy. Antipsychotics such as olanzapine, 5 to 10 mg nightly, or risperidone, 1 to 2 mg nightly, can decrease the delusional thoughts’ intensity and frequency, allowing patients to function more appropriately.³ If 2 or more antipsychotic trials do not control delusional thoughts, consider starting clozapine at 300 mg/d and titrating to 900 mg/d.

Add an antidepressant if delusional thinking causes depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, 10 to 20 mg/d, or fluoxetine, 20 to 40 mg/d, are a good starting point. Consider other antidepressant types if SSRIs do not work.

Adjunctive benzodiazepines such as clonazepam, 1 to 2 mg/d, or lorazepam, 1 to 2 mg bid as needed, can help manage acute anxiety or agitation stemming from delusions.

Psychotherapy. Supportive therapy can alleviate anxiety and depression that often result from delusional thinking. Cognitive-behavioral therapy can teach patients to stop acting on their delusions.

Once rapport is established, consider challenging delusional beliefs by having the patient list evidence supporting or refuting the delusions. Be careful not to confront delusional thinking too quickly or aggressively, as this approach often does not change the patient’s beliefs and weakens the therapeutic alliance.³

TREATMENT: Fewer complaints

We still see Ms. L every 3 weeks for supportive psychotherapy and medication management. We continue oxcarbazepine, 150 mg bid, and escitalopram, 30 mg/d, and add risperidone, 1 mg at bedtime, to target her delusional thinking, lability, and irritability.

Over 6 months, Ms. L’s complaints of abuse become less emphatic. She endorses the abuse less frequently—every 3 to 4 visits—and only if the clinician specifically asks about it. Most often, she denies abuse is occurring but says it happened previously. At each visit, we document her statements and explain in her chart why we have not notified adult protective services or police.

Related resources

• National Adult Protective Services Association. Links to adult protection agencies nationwide. www.apsnetwork.org.
  
• National Center on Elder Abuse. www.elderabusecenter.org.
  

 

Drug brand names

• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Oxcarbazepine • Trileptal
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  

Disclosure

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

HISTORY: Depressed and sick

Mr. T, age 53, was diagnosed last year with hepatitis C and for 20 years has battled recurrent major depression with euthymia between episodes. His hepatologist asks us to evaluate his recent depressed mood and erratic behavior.

Less than 2 months ago, the hepatologist prescribed ribavirin, 1,000 mg bid, and peginterferon alfa-2B, 10 million IU/1.0 mL weekly, for hepatitis C. Soon afterward, Mr. T became irritable, especially toward his wife. He now refuses to leave his house most days because of overwhelming sadness and hopelessness. Once an avid motorcycle enthusiast, Mr. T has stopped riding and complains of fatigue, “fuzzy” thinking, and diminished concentration, but he denies suicidal thoughts or intent. He weighs 232 lb but has lost 15 lb in the last 6 weeks.

Five weeks ago, the hepatologist added bupropion XL, 150 mg/d, for Mr. T’s depressive symptoms, but the patient complained that the antidepressant “amped me up” and “made my mind race.” After 3 weeks, the hepatologist switched to escitalopram, 10 mg/d, but Mr. T’s agitation continued.

Several days after starting escitalopram, Mr. T experienced what he calls a “pink cloud” period—intensely pleasurable episodes that he says began in late childhood, usually last about 4 days, and occur 6 times annually. During these episodes, his thoughts race, his speech is mildly pressured, and he sleeps 5 hours or less nightly. While euphoric, he drives his motorcycle at 100 mph, starts several projects at once, and is distractible.

Once the “pink clouds” clear, Mr. T feels fatigued and “let down” as he does now. He says he has never reported these euphoric periods because he usually enjoys them.

Mr. T also has longstanding anxiety. Most days he is “on edge” and restless, feels muscle tension in his neck, and has trouble falling and staying sleep. After changing jobs last year, he began having panic attacks triggered by excessive worry. He denies anticipatory fear or avoidance, so we rule out panic disorder.

Additionally, Mr. T has been engaging in weekly binge-eating episodes during which he consumes nearly 50 large-sized cookies and 2 to 3 2-ounce bags of potato chips in 2 hours. He is wracked with guilt after bingeing and often feels embarrassed about being overweight (body mass index, 31 kg/m²). He does not purge but moderately restricts his diet between binges. He says he started bingeing at age 20, and at one point was bingeing 3 times a week.

Mr. T also complains that ribavirin and peginterferon are causing headaches, fatigue, and myalgias. He also takes hydrochlorothiazide, 25 mg/d, for hypertension, and is allergic to sulfonamides. He denies using alcohol and drugs but smokes 2 packs of cigarettes per day.

We diagnose bipolar II disorder based on Mr. T’s extreme mood shifts, history of major depressive episodes, recent hypomania, lack of manic or mixed episodes, and significant distress. His hypomania episodes last <1 week; episodes that last ≥1 week or require hospitalization would signal bipolar I disorder.

We rule out interferon-induced depression and hypomania¹ because Mr. T showed signs of mood dysfunction long before he contracted hepatitis C. We also diagnose generalized anxiety disorder and eating disorder, not otherwise specified.

The authors’ observations

Diagnosing and managing bipolar disorder is challenging, especially when hypomania is not readily apparent.²

After we discuss treatment options with Mr. T, he chooses lamotrigine because it causes relatively few side effects and is less likely than valproic acid and other mood-stabilizing anticonvulsants to cause hepatotoxicity or pancreatitis.³ Lamotrigine also might reduce Mr. T’s anxiety.⁴

We do not try lithium because Mr. T is taking a diuretic (hydrochlorothiazide), which can cause lithium toxicity when used concomitantly. Also, lithium requires close laboratory monitoring, interacts with many medications, and can cause drowsiness, dry mouth, blurry vision, and fatigue.⁵ These
factors contraindicate lithium for Mr. T, who is taking several medications and suffers side effects from ribavirin and interferon.

Olanzapine might control Mr. T’s mood swings, but the neuroleptic can cause weight gain and metabolic syndrome⁶ and might complicate his eating disorder.

TREATMENT: A ‘rash’ reaction

We add lamotrigine, 25 mg/d, for 2 weeks and then increase to 50 mg/d.

Two days after the lamotrigine increase, Mr. T reports a rash on the left side of his trunk and left hip, buttock, and elbow (Figure). He also complains of mild chills and night sweats, although these symptoms emerged several weeks ago. He denies blistering, fevers, dysuria, nausea, or vomiting. We see no signs of lymphadenopathy, and mucosae are unaffected. Since he started lamotrigine, he says, he has not tried unfamiliar brands of shampoos, laundry detergents, or shower gels that might irritate his skin.

 

Figure: Did lamotrigine cause Mr. T’s rash?

Folliculocentric pustules around patient’s left elbow and throughout his left side.We have Mr. T come in that day for an emergency physical examination. At presentation, the rash appears infectious with isolated pustules throughout. We refer him to a dermatologist for same-day evaluation.

The authors’ observations

A rash is an immunologic reaction to an offending agent. If lamotrigine were causing the rash, lowering the dosage would not mitigate it.

We continued lamotrigine because the dermatologist could examine the rash within 24 hours of Mr. T’s complaint. Also, the agent was decreasing the patient’s mood, irritability, and anger. If we believed lamotrigine was causing the rash and could not obtain an immediate dermatology consult, we would have stopped the medication.

FOLLOW-UP: ‘Hot’ findings

During the patient history interview, the dermatologist discovers that Mr. T recently installed a whirlpool bath, and that the eruption occurred 3 to 5 days after the patient first used it. Physical examination shows groups of discrete folliculocentric pustules with surrounding erythema mainly on his extensor surfaces and left buttock. These findings and Mr. T’s history suggest a skin infection.

The dermatologist diagnoses hot tub folliculitis, an infection caused by exposure to contaminated whirlpools, hot tubs, or water slides. Cultures obtained that day grow Pseudomonas aeruginosa, confirming the diagnosis. The dermatologist tells Mr. T to stop using his whirlpool bath and prescribes topical gentamicin and ciprofloxacin, 500 mg bid for 10 days. We continue lamotrigine based on the dermatologist’s recommendation.

Two weeks later, Mr. T’s eruption resolves, and we increase lamotrigine to 100 mg/d, which improves his mood and achieves steady-state effectiveness.⁷ We continue escitalopram, 10 mg/d, then increase to 20 mg/d to treat his generalized anxiety. Mr. T begins experiencing anorgasmia 1 week after the escitalopram increase, so we switch to buspirone, 15 mg bid. After another 4 weeks, his anger, irritability, panic attacks, anxiety, and depression have diminished.

After 3 months, Mr. T’s hepatologist stops ribavirin and peginterferon because they are not helping his hepatitis C infection. Days later, Mr. T’s chills, sweats, and fatigue remit.

The hepatologist considers an experimental hepatitis C
medication.

We see Mr. T once monthly for supportive psychotherapy and medication management. Despite divorce proceedings and persistent mild depression he is optimistic, enjoys work, and rides his motorcycle safely twice a week.

The authors’ observations

Although Mr. T’s presentation and patient history clearly suggested an independent skin infection, distinguishing between an infection and anticonvulsant-induced rash can be difficult.

Lamotrigine and other antiepileptics (Table 1)⁸ have been associated with morbilliform eruptions, anticonvulsant hypersensitivity syndrome, erythema multiforme, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), a severe form of SJS with a 20% to 30% mortality rate.^9,10

Table 1

Estimated risk of severe rash among first-time antiepileptic users*

Drug	Total new users†	Total SJS/TEN cases	Risk per 10,000 new users
Carbamazepine	286,360	39	1.4
Lamotrigine	55,154	14	2.5
Phenobarbital	8,659	7	8.1
Phenytoin	36,171	30	8.3
Valproic acid	103,150	4	0.4
* Researchers reviewed records of patients hospitalized between 1998 and 2001 with SJS or TEN after using an anticonvulsant.
† Estimates based on number of dispensed prescriptions, average prescribed dosages, and duration of anticonvulsant use as recorded in Germany’s Mediplus database.
SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis
Source: Adapted from reference 8

Although most lamotrigine-induced cutaneous eruptions are mild or self-limited, some are severe and potentially fatal. In clinical trials, approximately 10% of patients receiving lamotrigine for epilepsy developed cutaneous reactions.¹¹ Among 3,348 patients with epilepsy who received lamotrigine, 11 (0.3%) required hospitalization for SJS or TEN.¹¹

Anticonvulsant hypersensitivity syndrome, estimated to occur once per 1,000 to 10,000 exposures to anticonvulsants,¹² can lead to fever, lymphadenopathy, hepatomegaly, and arthralgias. Although hypersensitivity to aromatic anticonvulsants such as phenytoin, carbamazepine, or phenobarbital is most common, hypersensitivity to lamotrigine also has been reported.^13,14

Roughly 90% of patients with anticonvulsant hypersensitivity syndrome develop leukocytosis with eosinophilia, and some develop leukocytosis with agranulocytosis.^15-17 Fulminant hepatitis can occur, which leads to most deaths associated with this syndrome.

4 steps to gauging rash

Taking a thorough history, examining the eruption, ordering liver function tests (LFTs) and a complete blood count (CBC), and referring the patient to a dermatologist are key to determining the seriousness of an eruption and planning treatment in patients taking anticonvulsants (Table 2). See the patient within 12 hours after he reports the rash, as SJS and TEN often progress rapidly.

 

Table 2

4 steps to determining rash severity and cause

Take a thorough history	Find out when eruption occurred and when patient started the anticonvulsant
	Ask about past rashes, other medicines, and family history of reactions to medications
	Find out if patient has had fever/chills, malaise, lymphadenopathy, or mucosal symptoms such as photophobia or dysuria
Examine the eruption	Examine for mucosal involvement, facial edema, and blistering; describe the symmetry and extent of involvement
	Look for systemic findings such as fever, chills, lymphadenopathy, and organomegaly
	Photograph the eruption for the dermatologist if possible
Order laboratory tests	Order liver function tests and complete blood count with differentials; assess for eosinophilia
Closely monitor patient	Stop anticonvulsant if history, physical findings suggest a drug-induced eruption
	Refer patient to a dermatologist

STEP 1: Take a thorough history

Ask the patient:

What medications are you taking? Because more than 100 medications could cause SJS or TEN, a detailed drug history is critical to determining whether a medication has induced the eruption.

When did you start taking the potentially offending medication? True lamotrigine-induced eruptions usually occur 5 days to 8 weeks after the first dose.¹⁰ SJS and TEN generally take 1 to 2 weeks to develop.

What is your current dosage? Has it increased or decreased recently? Rapid lamotrigine dosage escalations or use of lamotrigine with valproic acid can cause severe rash.^9,10,18 Valproic acid increases serum lamotrigine by inhibiting its hepatic metabolism, thereby raising side-effect risk. In clinical trials, 30% of patients who received both anticonvulsants developed a rash.¹⁰

Have any family members had rashes after taking an anticonvulsant? Compared with the general population, siblings and first-degree relatives of patients with anticonvulsant-related eruptions are at higher risk for this complication.¹⁹ Decreased epoxide hydrolase activity might negate these patients’ ability to detoxify the arene oxide metabolite, which can cause adverse effects if it accumulates.

Do you have other medical problems? Hepatitis C, for example, can theoretically increase lamotrigine’s half-life, thereby elevating side-effect risk.¹¹

Watch for anticonvulsant-related adverse events in patients with hepatic insufficiency because hepatitis might hinder anticonvulsant metabolism.²⁰ Other medical comorbidities—such as HIV infection and systemic lupus erythematosus—also could increase the risk of antiepileptic-induced rash.¹⁰

Have you had fever, chills, or other symptoms? Patients with SJS and TEN usually present with systemic symptoms such as malaise, rash, lymphadenopathy, mucosal lesions, and/or symptoms such as photophobia, difficulty swallowing, rectal erosions, or dysuria. Patients with anticonvulsant hypersensitivity syndrome typically have fever and associated arthralgias, skin pain, lymphadenopathy, or a burning sensation on their skin. These symptoms generally are absent in localized cutaneous infections.

STEP 2: Examine the eruption

Cutaneous SJS and TEN findings usually include abrupt onset of erythematous macules—which progress to targetoid lesions containing central bullae—followed by extensive epidermal necrosis. Superficial lip and mouth necrosis occur early, leading to severe stomatitis.

TEN and SJS can appear similar clinically, but TEN
covers >30% of body surface area, whereas SJS covers <10%.
Rashes that cover 10% to 30% of body surface suggest SJS-TEN overlap syndrome.

Anticonvulsant hypersensitivity syndrome usually manifests as
a morbilliform eruption on the face, arms, and/or torso. The
lesions might become edematous and progress to exfoliation or vesiculobullae. Facial edema is a hallmark of anticonvulsant hypersensitivity,^15,16 and pustules and/or erythroderma might also appear. Other warning signs include symmetrical widespread eruption and organomegaly.

STEP 3: Order laboratory tests

Check liver function and order a CBC with differential to measure eosinophils. Eosinophilia and abnormal LFT results can signal anticonvulsant hypersensitivity.

Eosinophils. A normal eosinophil count ranges between 0% and 5% of peripheral blood leukocytes in adults, at a count of 350 to 650/cm. Although upper limits of normal vary, values >500/cm suggest hypereosinophilia.²¹

LFTs. Normal aspartate aminotransferase and alanine aminotransferase levels are 0 to 42 U/L and 0 to 48 U/L, respectively. Any LFT elevation could signal anticonvulsant hypersensitivity syndrome.

STEP 4: Closely monitor the patient

Discontinue the anticonvulsant if findings suggest a cutaneous drug reaction, and contact the patient’s primary care physician or dermatologist immediately. Early consultation with a dermatologist can help determine the eruption’s cause and reveal therapeutic options.

Dr. Pejic is chief resident in the adult psychiatry residency program, Louisiana State University Health Sciences Center and Ochsner Clinic Foundation, New Orleans.

Dr. Klinger is a third-year dermatology resident, Dr. Conrad is assistant professor of clinical psychiatry, and Dr. Nesbitt is chairman, department of dermatology, Louisiana State University Health Sciences Center.

 

Related Resources

• High WA. Stevens-Johnson syndrome and toxic epidermal necrolysis in adults. UpToDate Online (version 15.1); June 9, 2007. www.uptodate.com.
• Martin KA, Krahn LE, Rosati MJ, Balan V. Hepatitis C: How to manage mood during interferon treatment. Current Psychiatry 2006;5(11):69-80. http://www.currentpsychiatry.com/article_pages.asp?AID=4553.

Drug Brand Names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Carbamazepine • Tegretol, Equetro, others
• Ciprofloxacin • Cipro, Proquin
• Escitalopram • Lexapro
• Hydrochlorothiazide • various
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Olanzapine • Zyprexa
• Peginterferon alfa-2B • PEG-Intron
• Phenytoin • Dilantin
• Ribavirin • Copegus, Rebetol, others
• Valproic acid • Depakote

Disclosure

Dr. Conrad receives research/grant support from AstraZeneca, Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, and Wyeth.

Drs. Pejic, Nesbitt, and Klinger report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

HISTORY: Depressed and sick

Mr. T, age 53, was diagnosed last year with hepatitis C and for 20 years has battled recurrent major depression with euthymia between episodes. His hepatologist asks us to evaluate his recent depressed mood and erratic behavior.

Less than 2 months ago, the hepatologist prescribed ribavirin, 1,000 mg bid, and peginterferon alfa-2B, 10 million IU/1.0 mL weekly, for hepatitis C. Soon afterward, Mr. T became irritable, especially toward his wife. He now refuses to leave his house most days because of overwhelming sadness and hopelessness. Once an avid motorcycle enthusiast, Mr. T has stopped riding and complains of fatigue, “fuzzy” thinking, and diminished concentration, but he denies suicidal thoughts or intent. He weighs 232 lb but has lost 15 lb in the last 6 weeks.

Five weeks ago, the hepatologist added bupropion XL, 150 mg/d, for Mr. T’s depressive symptoms, but the patient complained that the antidepressant “amped me up” and “made my mind race.” After 3 weeks, the hepatologist switched to escitalopram, 10 mg/d, but Mr. T’s agitation continued.

Several days after starting escitalopram, Mr. T experienced what he calls a “pink cloud” period—intensely pleasurable episodes that he says began in late childhood, usually last about 4 days, and occur 6 times annually. During these episodes, his thoughts race, his speech is mildly pressured, and he sleeps 5 hours or less nightly. While euphoric, he drives his motorcycle at 100 mph, starts several projects at once, and is distractible.

Once the “pink clouds” clear, Mr. T feels fatigued and “let down” as he does now. He says he has never reported these euphoric periods because he usually enjoys them.

Mr. T also has longstanding anxiety. Most days he is “on edge” and restless, feels muscle tension in his neck, and has trouble falling and staying sleep. After changing jobs last year, he began having panic attacks triggered by excessive worry. He denies anticipatory fear or avoidance, so we rule out panic disorder.

Additionally, Mr. T has been engaging in weekly binge-eating episodes during which he consumes nearly 50 large-sized cookies and 2 to 3 2-ounce bags of potato chips in 2 hours. He is wracked with guilt after bingeing and often feels embarrassed about being overweight (body mass index, 31 kg/m²). He does not purge but moderately restricts his diet between binges. He says he started bingeing at age 20, and at one point was bingeing 3 times a week.

Mr. T also complains that ribavirin and peginterferon are causing headaches, fatigue, and myalgias. He also takes hydrochlorothiazide, 25 mg/d, for hypertension, and is allergic to sulfonamides. He denies using alcohol and drugs but smokes 2 packs of cigarettes per day.

We diagnose bipolar II disorder based on Mr. T’s extreme mood shifts, history of major depressive episodes, recent hypomania, lack of manic or mixed episodes, and significant distress. His hypomania episodes last <1 week; episodes that last ≥1 week or require hospitalization would signal bipolar I disorder.

We rule out interferon-induced depression and hypomania¹ because Mr. T showed signs of mood dysfunction long before he contracted hepatitis C. We also diagnose generalized anxiety disorder and eating disorder, not otherwise specified.

The authors’ observations

Diagnosing and managing bipolar disorder is challenging, especially when hypomania is not readily apparent.²

After we discuss treatment options with Mr. T, he chooses lamotrigine because it causes relatively few side effects and is less likely than valproic acid and other mood-stabilizing anticonvulsants to cause hepatotoxicity or pancreatitis.³ Lamotrigine also might reduce Mr. T’s anxiety.⁴

We do not try lithium because Mr. T is taking a diuretic (hydrochlorothiazide), which can cause lithium toxicity when used concomitantly. Also, lithium requires close laboratory monitoring, interacts with many medications, and can cause drowsiness, dry mouth, blurry vision, and fatigue.⁵ These
factors contraindicate lithium for Mr. T, who is taking several medications and suffers side effects from ribavirin and interferon.

Olanzapine might control Mr. T’s mood swings, but the neuroleptic can cause weight gain and metabolic syndrome⁶ and might complicate his eating disorder.

TREATMENT: A ‘rash’ reaction

We add lamotrigine, 25 mg/d, for 2 weeks and then increase to 50 mg/d.

Two days after the lamotrigine increase, Mr. T reports a rash on the left side of his trunk and left hip, buttock, and elbow (Figure). He also complains of mild chills and night sweats, although these symptoms emerged several weeks ago. He denies blistering, fevers, dysuria, nausea, or vomiting. We see no signs of lymphadenopathy, and mucosae are unaffected. Since he started lamotrigine, he says, he has not tried unfamiliar brands of shampoos, laundry detergents, or shower gels that might irritate his skin.

 

Figure: Did lamotrigine cause Mr. T’s rash?

Folliculocentric pustules around patient’s left elbow and throughout his left side.We have Mr. T come in that day for an emergency physical examination. At presentation, the rash appears infectious with isolated pustules throughout. We refer him to a dermatologist for same-day evaluation.

The authors’ observations

A rash is an immunologic reaction to an offending agent. If lamotrigine were causing the rash, lowering the dosage would not mitigate it.

We continued lamotrigine because the dermatologist could examine the rash within 24 hours of Mr. T’s complaint. Also, the agent was decreasing the patient’s mood, irritability, and anger. If we believed lamotrigine was causing the rash and could not obtain an immediate dermatology consult, we would have stopped the medication.

FOLLOW-UP: ‘Hot’ findings

During the patient history interview, the dermatologist discovers that Mr. T recently installed a whirlpool bath, and that the eruption occurred 3 to 5 days after the patient first used it. Physical examination shows groups of discrete folliculocentric pustules with surrounding erythema mainly on his extensor surfaces and left buttock. These findings and Mr. T’s history suggest a skin infection.

The dermatologist diagnoses hot tub folliculitis, an infection caused by exposure to contaminated whirlpools, hot tubs, or water slides. Cultures obtained that day grow Pseudomonas aeruginosa, confirming the diagnosis. The dermatologist tells Mr. T to stop using his whirlpool bath and prescribes topical gentamicin and ciprofloxacin, 500 mg bid for 10 days. We continue lamotrigine based on the dermatologist’s recommendation.

Two weeks later, Mr. T’s eruption resolves, and we increase lamotrigine to 100 mg/d, which improves his mood and achieves steady-state effectiveness.⁷ We continue escitalopram, 10 mg/d, then increase to 20 mg/d to treat his generalized anxiety. Mr. T begins experiencing anorgasmia 1 week after the escitalopram increase, so we switch to buspirone, 15 mg bid. After another 4 weeks, his anger, irritability, panic attacks, anxiety, and depression have diminished.

After 3 months, Mr. T’s hepatologist stops ribavirin and peginterferon because they are not helping his hepatitis C infection. Days later, Mr. T’s chills, sweats, and fatigue remit.

The hepatologist considers an experimental hepatitis C
medication.

We see Mr. T once monthly for supportive psychotherapy and medication management. Despite divorce proceedings and persistent mild depression he is optimistic, enjoys work, and rides his motorcycle safely twice a week.

The authors’ observations

Although Mr. T’s presentation and patient history clearly suggested an independent skin infection, distinguishing between an infection and anticonvulsant-induced rash can be difficult.

Lamotrigine and other antiepileptics (Table 1)⁸ have been associated with morbilliform eruptions, anticonvulsant hypersensitivity syndrome, erythema multiforme, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), a severe form of SJS with a 20% to 30% mortality rate.^9,10

Table 1

Estimated risk of severe rash among first-time antiepileptic users*

Drug	Total new users†	Total SJS/TEN cases	Risk per 10,000 new users
Carbamazepine	286,360	39	1.4
Lamotrigine	55,154	14	2.5
Phenobarbital	8,659	7	8.1
Phenytoin	36,171	30	8.3
Valproic acid	103,150	4	0.4
* Researchers reviewed records of patients hospitalized between 1998 and 2001 with SJS or TEN after using an anticonvulsant.
† Estimates based on number of dispensed prescriptions, average prescribed dosages, and duration of anticonvulsant use as recorded in Germany’s Mediplus database.
SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis
Source: Adapted from reference 8

Although most lamotrigine-induced cutaneous eruptions are mild or self-limited, some are severe and potentially fatal. In clinical trials, approximately 10% of patients receiving lamotrigine for epilepsy developed cutaneous reactions.¹¹ Among 3,348 patients with epilepsy who received lamotrigine, 11 (0.3%) required hospitalization for SJS or TEN.¹¹

Anticonvulsant hypersensitivity syndrome, estimated to occur once per 1,000 to 10,000 exposures to anticonvulsants,¹² can lead to fever, lymphadenopathy, hepatomegaly, and arthralgias. Although hypersensitivity to aromatic anticonvulsants such as phenytoin, carbamazepine, or phenobarbital is most common, hypersensitivity to lamotrigine also has been reported.^13,14

Roughly 90% of patients with anticonvulsant hypersensitivity syndrome develop leukocytosis with eosinophilia, and some develop leukocytosis with agranulocytosis.^15-17 Fulminant hepatitis can occur, which leads to most deaths associated with this syndrome.

4 steps to gauging rash

Taking a thorough history, examining the eruption, ordering liver function tests (LFTs) and a complete blood count (CBC), and referring the patient to a dermatologist are key to determining the seriousness of an eruption and planning treatment in patients taking anticonvulsants (Table 2). See the patient within 12 hours after he reports the rash, as SJS and TEN often progress rapidly.

 

Table 2

4 steps to determining rash severity and cause

Take a thorough history	Find out when eruption occurred and when patient started the anticonvulsant
	Ask about past rashes, other medicines, and family history of reactions to medications
	Find out if patient has had fever/chills, malaise, lymphadenopathy, or mucosal symptoms such as photophobia or dysuria
Examine the eruption	Examine for mucosal involvement, facial edema, and blistering; describe the symmetry and extent of involvement
	Look for systemic findings such as fever, chills, lymphadenopathy, and organomegaly
	Photograph the eruption for the dermatologist if possible
Order laboratory tests	Order liver function tests and complete blood count with differentials; assess for eosinophilia
Closely monitor patient	Stop anticonvulsant if history, physical findings suggest a drug-induced eruption
	Refer patient to a dermatologist

STEP 1: Take a thorough history

Ask the patient:

What medications are you taking? Because more than 100 medications could cause SJS or TEN, a detailed drug history is critical to determining whether a medication has induced the eruption.

When did you start taking the potentially offending medication? True lamotrigine-induced eruptions usually occur 5 days to 8 weeks after the first dose.¹⁰ SJS and TEN generally take 1 to 2 weeks to develop.

What is your current dosage? Has it increased or decreased recently? Rapid lamotrigine dosage escalations or use of lamotrigine with valproic acid can cause severe rash.^9,10,18 Valproic acid increases serum lamotrigine by inhibiting its hepatic metabolism, thereby raising side-effect risk. In clinical trials, 30% of patients who received both anticonvulsants developed a rash.¹⁰

Have any family members had rashes after taking an anticonvulsant? Compared with the general population, siblings and first-degree relatives of patients with anticonvulsant-related eruptions are at higher risk for this complication.¹⁹ Decreased epoxide hydrolase activity might negate these patients’ ability to detoxify the arene oxide metabolite, which can cause adverse effects if it accumulates.

Do you have other medical problems? Hepatitis C, for example, can theoretically increase lamotrigine’s half-life, thereby elevating side-effect risk.¹¹

Watch for anticonvulsant-related adverse events in patients with hepatic insufficiency because hepatitis might hinder anticonvulsant metabolism.²⁰ Other medical comorbidities—such as HIV infection and systemic lupus erythematosus—also could increase the risk of antiepileptic-induced rash.¹⁰

Have you had fever, chills, or other symptoms? Patients with SJS and TEN usually present with systemic symptoms such as malaise, rash, lymphadenopathy, mucosal lesions, and/or symptoms such as photophobia, difficulty swallowing, rectal erosions, or dysuria. Patients with anticonvulsant hypersensitivity syndrome typically have fever and associated arthralgias, skin pain, lymphadenopathy, or a burning sensation on their skin. These symptoms generally are absent in localized cutaneous infections.

STEP 2: Examine the eruption

Cutaneous SJS and TEN findings usually include abrupt onset of erythematous macules—which progress to targetoid lesions containing central bullae—followed by extensive epidermal necrosis. Superficial lip and mouth necrosis occur early, leading to severe stomatitis.

TEN and SJS can appear similar clinically, but TEN
covers >30% of body surface area, whereas SJS covers <10%.
Rashes that cover 10% to 30% of body surface suggest SJS-TEN overlap syndrome.

Anticonvulsant hypersensitivity syndrome usually manifests as
a morbilliform eruption on the face, arms, and/or torso. The
lesions might become edematous and progress to exfoliation or vesiculobullae. Facial edema is a hallmark of anticonvulsant hypersensitivity,^15,16 and pustules and/or erythroderma might also appear. Other warning signs include symmetrical widespread eruption and organomegaly.

STEP 3: Order laboratory tests

Check liver function and order a CBC with differential to measure eosinophils. Eosinophilia and abnormal LFT results can signal anticonvulsant hypersensitivity.

Eosinophils. A normal eosinophil count ranges between 0% and 5% of peripheral blood leukocytes in adults, at a count of 350 to 650/cm. Although upper limits of normal vary, values >500/cm suggest hypereosinophilia.²¹

LFTs. Normal aspartate aminotransferase and alanine aminotransferase levels are 0 to 42 U/L and 0 to 48 U/L, respectively. Any LFT elevation could signal anticonvulsant hypersensitivity syndrome.

STEP 4: Closely monitor the patient

Discontinue the anticonvulsant if findings suggest a cutaneous drug reaction, and contact the patient’s primary care physician or dermatologist immediately. Early consultation with a dermatologist can help determine the eruption’s cause and reveal therapeutic options.

Dr. Pejic is chief resident in the adult psychiatry residency program, Louisiana State University Health Sciences Center and Ochsner Clinic Foundation, New Orleans.

Dr. Klinger is a third-year dermatology resident, Dr. Conrad is assistant professor of clinical psychiatry, and Dr. Nesbitt is chairman, department of dermatology, Louisiana State University Health Sciences Center.

 

Related Resources

• High WA. Stevens-Johnson syndrome and toxic epidermal necrolysis in adults. UpToDate Online (version 15.1); June 9, 2007. www.uptodate.com.
• Martin KA, Krahn LE, Rosati MJ, Balan V. Hepatitis C: How to manage mood during interferon treatment. Current Psychiatry 2006;5(11):69-80. http://www.currentpsychiatry.com/article_pages.asp?AID=4553.

Drug Brand Names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Carbamazepine • Tegretol, Equetro, others
• Ciprofloxacin • Cipro, Proquin
• Escitalopram • Lexapro
• Hydrochlorothiazide • various
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Olanzapine • Zyprexa
• Peginterferon alfa-2B • PEG-Intron
• Phenytoin • Dilantin
• Ribavirin • Copegus, Rebetol, others
• Valproic acid • Depakote

Disclosure

Dr. Conrad receives research/grant support from AstraZeneca, Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, and Wyeth.

Drs. Pejic, Nesbitt, and Klinger report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

HISTORY: Depressed and sick

Mr. T, age 53, was diagnosed last year with hepatitis C and for 20 years has battled recurrent major depression with euthymia between episodes. His hepatologist asks us to evaluate his recent depressed mood and erratic behavior.

Less than 2 months ago, the hepatologist prescribed ribavirin, 1,000 mg bid, and peginterferon alfa-2B, 10 million IU/1.0 mL weekly, for hepatitis C. Soon afterward, Mr. T became irritable, especially toward his wife. He now refuses to leave his house most days because of overwhelming sadness and hopelessness. Once an avid motorcycle enthusiast, Mr. T has stopped riding and complains of fatigue, “fuzzy” thinking, and diminished concentration, but he denies suicidal thoughts or intent. He weighs 232 lb but has lost 15 lb in the last 6 weeks.

Five weeks ago, the hepatologist added bupropion XL, 150 mg/d, for Mr. T’s depressive symptoms, but the patient complained that the antidepressant “amped me up” and “made my mind race.” After 3 weeks, the hepatologist switched to escitalopram, 10 mg/d, but Mr. T’s agitation continued.

Several days after starting escitalopram, Mr. T experienced what he calls a “pink cloud” period—intensely pleasurable episodes that he says began in late childhood, usually last about 4 days, and occur 6 times annually. During these episodes, his thoughts race, his speech is mildly pressured, and he sleeps 5 hours or less nightly. While euphoric, he drives his motorcycle at 100 mph, starts several projects at once, and is distractible.

Once the “pink clouds” clear, Mr. T feels fatigued and “let down” as he does now. He says he has never reported these euphoric periods because he usually enjoys them.

Mr. T also has longstanding anxiety. Most days he is “on edge” and restless, feels muscle tension in his neck, and has trouble falling and staying sleep. After changing jobs last year, he began having panic attacks triggered by excessive worry. He denies anticipatory fear or avoidance, so we rule out panic disorder.

Additionally, Mr. T has been engaging in weekly binge-eating episodes during which he consumes nearly 50 large-sized cookies and 2 to 3 2-ounce bags of potato chips in 2 hours. He is wracked with guilt after bingeing and often feels embarrassed about being overweight (body mass index, 31 kg/m²). He does not purge but moderately restricts his diet between binges. He says he started bingeing at age 20, and at one point was bingeing 3 times a week.

Mr. T also complains that ribavirin and peginterferon are causing headaches, fatigue, and myalgias. He also takes hydrochlorothiazide, 25 mg/d, for hypertension, and is allergic to sulfonamides. He denies using alcohol and drugs but smokes 2 packs of cigarettes per day.

We diagnose bipolar II disorder based on Mr. T’s extreme mood shifts, history of major depressive episodes, recent hypomania, lack of manic or mixed episodes, and significant distress. His hypomania episodes last <1 week; episodes that last ≥1 week or require hospitalization would signal bipolar I disorder.

We rule out interferon-induced depression and hypomania¹ because Mr. T showed signs of mood dysfunction long before he contracted hepatitis C. We also diagnose generalized anxiety disorder and eating disorder, not otherwise specified.

The authors’ observations

Diagnosing and managing bipolar disorder is challenging, especially when hypomania is not readily apparent.²

After we discuss treatment options with Mr. T, he chooses lamotrigine because it causes relatively few side effects and is less likely than valproic acid and other mood-stabilizing anticonvulsants to cause hepatotoxicity or pancreatitis.³ Lamotrigine also might reduce Mr. T’s anxiety.⁴

We do not try lithium because Mr. T is taking a diuretic (hydrochlorothiazide), which can cause lithium toxicity when used concomitantly. Also, lithium requires close laboratory monitoring, interacts with many medications, and can cause drowsiness, dry mouth, blurry vision, and fatigue.⁵ These
factors contraindicate lithium for Mr. T, who is taking several medications and suffers side effects from ribavirin and interferon.

Olanzapine might control Mr. T’s mood swings, but the neuroleptic can cause weight gain and metabolic syndrome⁶ and might complicate his eating disorder.

TREATMENT: A ‘rash’ reaction

We add lamotrigine, 25 mg/d, for 2 weeks and then increase to 50 mg/d.

Two days after the lamotrigine increase, Mr. T reports a rash on the left side of his trunk and left hip, buttock, and elbow (Figure). He also complains of mild chills and night sweats, although these symptoms emerged several weeks ago. He denies blistering, fevers, dysuria, nausea, or vomiting. We see no signs of lymphadenopathy, and mucosae are unaffected. Since he started lamotrigine, he says, he has not tried unfamiliar brands of shampoos, laundry detergents, or shower gels that might irritate his skin.

 

Figure: Did lamotrigine cause Mr. T’s rash?

Folliculocentric pustules around patient’s left elbow and throughout his left side.We have Mr. T come in that day for an emergency physical examination. At presentation, the rash appears infectious with isolated pustules throughout. We refer him to a dermatologist for same-day evaluation.

The authors’ observations

A rash is an immunologic reaction to an offending agent. If lamotrigine were causing the rash, lowering the dosage would not mitigate it.

We continued lamotrigine because the dermatologist could examine the rash within 24 hours of Mr. T’s complaint. Also, the agent was decreasing the patient’s mood, irritability, and anger. If we believed lamotrigine was causing the rash and could not obtain an immediate dermatology consult, we would have stopped the medication.

FOLLOW-UP: ‘Hot’ findings

During the patient history interview, the dermatologist discovers that Mr. T recently installed a whirlpool bath, and that the eruption occurred 3 to 5 days after the patient first used it. Physical examination shows groups of discrete folliculocentric pustules with surrounding erythema mainly on his extensor surfaces and left buttock. These findings and Mr. T’s history suggest a skin infection.

The dermatologist diagnoses hot tub folliculitis, an infection caused by exposure to contaminated whirlpools, hot tubs, or water slides. Cultures obtained that day grow Pseudomonas aeruginosa, confirming the diagnosis. The dermatologist tells Mr. T to stop using his whirlpool bath and prescribes topical gentamicin and ciprofloxacin, 500 mg bid for 10 days. We continue lamotrigine based on the dermatologist’s recommendation.

Two weeks later, Mr. T’s eruption resolves, and we increase lamotrigine to 100 mg/d, which improves his mood and achieves steady-state effectiveness.⁷ We continue escitalopram, 10 mg/d, then increase to 20 mg/d to treat his generalized anxiety. Mr. T begins experiencing anorgasmia 1 week after the escitalopram increase, so we switch to buspirone, 15 mg bid. After another 4 weeks, his anger, irritability, panic attacks, anxiety, and depression have diminished.

After 3 months, Mr. T’s hepatologist stops ribavirin and peginterferon because they are not helping his hepatitis C infection. Days later, Mr. T’s chills, sweats, and fatigue remit.

The hepatologist considers an experimental hepatitis C
medication.

We see Mr. T once monthly for supportive psychotherapy and medication management. Despite divorce proceedings and persistent mild depression he is optimistic, enjoys work, and rides his motorcycle safely twice a week.

The authors’ observations

Although Mr. T’s presentation and patient history clearly suggested an independent skin infection, distinguishing between an infection and anticonvulsant-induced rash can be difficult.

Lamotrigine and other antiepileptics (Table 1)⁸ have been associated with morbilliform eruptions, anticonvulsant hypersensitivity syndrome, erythema multiforme, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), a severe form of SJS with a 20% to 30% mortality rate.^9,10

Table 1

Estimated risk of severe rash among first-time antiepileptic users*

Drug	Total new users†	Total SJS/TEN cases	Risk per 10,000 new users
Carbamazepine	286,360	39	1.4
Lamotrigine	55,154	14	2.5
Phenobarbital	8,659	7	8.1
Phenytoin	36,171	30	8.3
Valproic acid	103,150	4	0.4
* Researchers reviewed records of patients hospitalized between 1998 and 2001 with SJS or TEN after using an anticonvulsant.
† Estimates based on number of dispensed prescriptions, average prescribed dosages, and duration of anticonvulsant use as recorded in Germany’s Mediplus database.
SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis
Source: Adapted from reference 8

Although most lamotrigine-induced cutaneous eruptions are mild or self-limited, some are severe and potentially fatal. In clinical trials, approximately 10% of patients receiving lamotrigine for epilepsy developed cutaneous reactions.¹¹ Among 3,348 patients with epilepsy who received lamotrigine, 11 (0.3%) required hospitalization for SJS or TEN.¹¹

Anticonvulsant hypersensitivity syndrome, estimated to occur once per 1,000 to 10,000 exposures to anticonvulsants,¹² can lead to fever, lymphadenopathy, hepatomegaly, and arthralgias. Although hypersensitivity to aromatic anticonvulsants such as phenytoin, carbamazepine, or phenobarbital is most common, hypersensitivity to lamotrigine also has been reported.^13,14

Roughly 90% of patients with anticonvulsant hypersensitivity syndrome develop leukocytosis with eosinophilia, and some develop leukocytosis with agranulocytosis.^15-17 Fulminant hepatitis can occur, which leads to most deaths associated with this syndrome.

4 steps to gauging rash

Taking a thorough history, examining the eruption, ordering liver function tests (LFTs) and a complete blood count (CBC), and referring the patient to a dermatologist are key to determining the seriousness of an eruption and planning treatment in patients taking anticonvulsants (Table 2). See the patient within 12 hours after he reports the rash, as SJS and TEN often progress rapidly.

 

Table 2

4 steps to determining rash severity and cause

Take a thorough history	Find out when eruption occurred and when patient started the anticonvulsant
	Ask about past rashes, other medicines, and family history of reactions to medications
	Find out if patient has had fever/chills, malaise, lymphadenopathy, or mucosal symptoms such as photophobia or dysuria
Examine the eruption	Examine for mucosal involvement, facial edema, and blistering; describe the symmetry and extent of involvement
	Look for systemic findings such as fever, chills, lymphadenopathy, and organomegaly
	Photograph the eruption for the dermatologist if possible
Order laboratory tests	Order liver function tests and complete blood count with differentials; assess for eosinophilia
Closely monitor patient	Stop anticonvulsant if history, physical findings suggest a drug-induced eruption
	Refer patient to a dermatologist

STEP 1: Take a thorough history

Ask the patient:

What medications are you taking? Because more than 100 medications could cause SJS or TEN, a detailed drug history is critical to determining whether a medication has induced the eruption.

When did you start taking the potentially offending medication? True lamotrigine-induced eruptions usually occur 5 days to 8 weeks after the first dose.¹⁰ SJS and TEN generally take 1 to 2 weeks to develop.

What is your current dosage? Has it increased or decreased recently? Rapid lamotrigine dosage escalations or use of lamotrigine with valproic acid can cause severe rash.^9,10,18 Valproic acid increases serum lamotrigine by inhibiting its hepatic metabolism, thereby raising side-effect risk. In clinical trials, 30% of patients who received both anticonvulsants developed a rash.¹⁰

Have any family members had rashes after taking an anticonvulsant? Compared with the general population, siblings and first-degree relatives of patients with anticonvulsant-related eruptions are at higher risk for this complication.¹⁹ Decreased epoxide hydrolase activity might negate these patients’ ability to detoxify the arene oxide metabolite, which can cause adverse effects if it accumulates.

Do you have other medical problems? Hepatitis C, for example, can theoretically increase lamotrigine’s half-life, thereby elevating side-effect risk.¹¹

Watch for anticonvulsant-related adverse events in patients with hepatic insufficiency because hepatitis might hinder anticonvulsant metabolism.²⁰ Other medical comorbidities—such as HIV infection and systemic lupus erythematosus—also could increase the risk of antiepileptic-induced rash.¹⁰

Have you had fever, chills, or other symptoms? Patients with SJS and TEN usually present with systemic symptoms such as malaise, rash, lymphadenopathy, mucosal lesions, and/or symptoms such as photophobia, difficulty swallowing, rectal erosions, or dysuria. Patients with anticonvulsant hypersensitivity syndrome typically have fever and associated arthralgias, skin pain, lymphadenopathy, or a burning sensation on their skin. These symptoms generally are absent in localized cutaneous infections.

STEP 2: Examine the eruption

Cutaneous SJS and TEN findings usually include abrupt onset of erythematous macules—which progress to targetoid lesions containing central bullae—followed by extensive epidermal necrosis. Superficial lip and mouth necrosis occur early, leading to severe stomatitis.

TEN and SJS can appear similar clinically, but TEN
covers >30% of body surface area, whereas SJS covers <10%.
Rashes that cover 10% to 30% of body surface suggest SJS-TEN overlap syndrome.

Anticonvulsant hypersensitivity syndrome usually manifests as
a morbilliform eruption on the face, arms, and/or torso. The
lesions might become edematous and progress to exfoliation or vesiculobullae. Facial edema is a hallmark of anticonvulsant hypersensitivity,^15,16 and pustules and/or erythroderma might also appear. Other warning signs include symmetrical widespread eruption and organomegaly.

STEP 3: Order laboratory tests

Check liver function and order a CBC with differential to measure eosinophils. Eosinophilia and abnormal LFT results can signal anticonvulsant hypersensitivity.

Eosinophils. A normal eosinophil count ranges between 0% and 5% of peripheral blood leukocytes in adults, at a count of 350 to 650/cm. Although upper limits of normal vary, values >500/cm suggest hypereosinophilia.²¹

LFTs. Normal aspartate aminotransferase and alanine aminotransferase levels are 0 to 42 U/L and 0 to 48 U/L, respectively. Any LFT elevation could signal anticonvulsant hypersensitivity syndrome.

STEP 4: Closely monitor the patient

Discontinue the anticonvulsant if findings suggest a cutaneous drug reaction, and contact the patient’s primary care physician or dermatologist immediately. Early consultation with a dermatologist can help determine the eruption’s cause and reveal therapeutic options.

Dr. Pejic is chief resident in the adult psychiatry residency program, Louisiana State University Health Sciences Center and Ochsner Clinic Foundation, New Orleans.

Dr. Klinger is a third-year dermatology resident, Dr. Conrad is assistant professor of clinical psychiatry, and Dr. Nesbitt is chairman, department of dermatology, Louisiana State University Health Sciences Center.

 

Related Resources

• High WA. Stevens-Johnson syndrome and toxic epidermal necrolysis in adults. UpToDate Online (version 15.1); June 9, 2007. www.uptodate.com.
• Martin KA, Krahn LE, Rosati MJ, Balan V. Hepatitis C: How to manage mood during interferon treatment. Current Psychiatry 2006;5(11):69-80. http://www.currentpsychiatry.com/article_pages.asp?AID=4553.

Drug Brand Names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Carbamazepine • Tegretol, Equetro, others
• Ciprofloxacin • Cipro, Proquin
• Escitalopram • Lexapro
• Hydrochlorothiazide • various
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Olanzapine • Zyprexa
• Peginterferon alfa-2B • PEG-Intron
• Phenytoin • Dilantin
• Ribavirin • Copegus, Rebetol, others
• Valproic acid • Depakote

Disclosure

Dr. Conrad receives research/grant support from AstraZeneca, Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, and Wyeth.

Drs. Pejic, Nesbitt, and Klinger report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

HISTORY: ‘Bizarre’ days

Ms. K, age 45, is brought to the ER by her brother, who reports she has been acting “bizarre and crazy” for 3 days. He says his sister—who has bipolar I disorder— has had trouble sleeping, is restless, hears voices, and is contemplating suicide. He adds she was discharged from a psychiatric hospital 2 weeks ago after a 3-month stay.

Risperidone, 2 mg nightly, was controlling Ms. K’s mania until this recent episode. According to her brother, she also has developed continuous involuntary leg and arm movements and cannot sit or stand still. When she tries to sleep, her feet sway back and forth in bed for hours.

We admit Ms. K to the psychiatric inpatient unit because of her suicidality and hallucinations. She is restless and agitated during initial evaluation, pacing around the room or rocking her feet while standing or sitting. Her speech is pressured and the “voices” are urging her to kill herself.

Ms. K is dysphoric and severely distraught about her “nervousness” and continuous urges to move. She says she would rather die than live with incessantly “jittery” legs and arms, yet she wants to be discharged and denies that she is mentally ill. She believes decreased sleep is causing her symptoms and requests a “sleeping pill.”

Ms. K was diagnosed with bipolar I disorder in her late 20s. During manic episodes she goes on spending sprees, makes reckless investments, and gambles impulsively. She has long battled euphoric/irritable mood and paranoid delusions, but
she habitually views her medications as useless and stops taking them.

The patient has been hospitalized at least 4 times with severe manic and psychotic symptoms. She does not use illicit drugs and is medically healthy.

The authors’ observations

Ms. K’s involuntary movements suggest akathisia, a common extrapyramidal side effect of antipsychotics and other psychotropics (Table).¹

Akathisia is characterized by strong feelings of inner restlessness that manifest as excessive walking or pacing and difficulty remaining still. Ms. K’s movements met at least 2 of 5 DSM-IV-TR criteria for acute akathisia (Box). ,²

Akathisia is characterized by at least 5 subtypes: ³

• Acute akathisia begins hours or days after starting the offending medication and lasts
• Tardive is similar to acute akathisia but can arise within 3 to 4 months of starting the offending medication and persists for years.
  
• Chronic akathisia lasts ≥3 months and usually has no temporal correlation with antipsychotic initiation or dosage increase.⁴
  
• Withdrawal akathisia begins within 6 weeks of discontinuing a medication or significantly reducing the dosage.
  
• Pseudo akathisia consists of objective symptoms of movement without subjective awareness or distress. This subtype usually is seen in older patients.
  

Patient history is critical to determining akathisia subtype. Ms. K’s sudden onset of manic and movement symptoms and
history of medication nonadherence strongly suggest akathisia secondary to risperidone withdrawal.⁵ Several
cases of akathisia after risperidone cessation have been reported.⁵

We know risperidone is not causing acute akathisia because Ms. K responded well to the medication during her last hospitalization with no adverse effects. Also, her family confirmed that she stopped taking risperidone after her most recent discharge.

Mania also can fuel incessant movement and increase physical activity, but patients often do not realize they have a problem while in a manic phase. Also, swinging and rocking of legs is rarely seen in mania. By contrast, Ms. K was morbidly distraught over her akathisia.

Table

Drugs that can cause akathisia

Dopamine receptor agonists (such as antiparkinsons agents) Carbidopa/levodopa Ethosuximide Metoclopramide Neuroleptics Reserpine Selective serotonin reuptake inhibitors

The authors’ observations

Numerous treatments are available for akathisia:

Beta blockers such as propranolol are most widely used because of their rapid onset of action and overall effectiveness in akathisia.³ Researchers believe these drugs reduce extrapyramidal symptoms (EPS) by blocking the adrenergic system. Propranolol can be used at a maximum 120 mg/d in divided doses.

Beta blockers, however, can cause bradycardia, hypotension, or respiratory distress. Use beta blockers with caution, and monitor for these adverse effects.

Benzodiazepines. Clonazepam, which enhances the inhibitory effect of GABA in the brain, is commonly used for akathisia because of its effectiveness and long elimination half-life³ (30 to 40 hours), which decreases the risk of medication withdrawal.

Patients, however, can develop a tolerance to clonazepam and become addicted to it. Use clonazepam with caution in patients with past substance abuse, and watch for sedation, fatigue,

 

and disinhibition-induced aggression in all patients.

Anticholinergics such as trihexyphenidyl are more commonly used for EPS associated with parkinsonian symptoms or side effects but can be partially effective for akathisia.³ Anticholinergics block the CNS cholinergic activity that causes parkinsonian symptoms.

Cyproheptadine, clonidine, and mianserin have shown some positive results against akathisia in clinical trials.^6-8 Iron, nicotine patches, and amantadine have shown limited effectiveness against akathisia in research studies and case reports.^3,9

Restarting risperidone at a lower dosage—rather than adding a medication— might have resolved Ms. K’s akathisia, but because she was morbidly despondent over her akathisia, we felt we had no time to experiment. We also believed Ms. K’s would respond well to a neuroleptic with a lower EPS risk—such as quetiapine.^1,10

Box

TREATMENT: Trying trials

We perform a complete medical workup to rule out an underlying medical problem. We then start valproic acid, 500 mg bid, for Ms. K’s mania; quetiapine, 50 mg bid, for psychosis and mania; and propranolol, 30 mg bid, for akathisia.

We titrate quetiapine by 100 mg/d every 2 days to 400 mg/d, but after 10 days her akathisia, irritable mood, decreased sleep, and suicidal thoughts persist. We cannot increase propranolol because her blood pressure is 90/60 mm Hg, and adding lorazepam, 0.5 mg tid, does not control her movements. Three days later, we add trihexyphenidyl, 5 mg bid.

Fifteen days after admission, Ms. K remains akathisic, dysphoric, and suicidal despite a 5-drug regimen. Her “nervousness” prevents her from attending groups or other unit activities, and her uncontrollable foot swaying still keeps her awake at night.

The authors’ observations

Neither propranolol, clonazepam, nor trihexyphenidyl alleviated Ms. K’s akathisia. Switching to another neuroleptic with a relatively low EPS risk—such as olanzapine—might help. Olanzapine reduced akathisia in 3 case reports,¹¹ and we hope its strong anticholinergic and antiserotonergic action will help resolve Ms. K’s akathisia.

Patients treated with therapeutic dosages of olanzapine have shown increased muscarinic receptor occupancy compared
with patients receiving therapeutic dosages of risperidone.¹² In another study, olanzapine showed anticholinergic activity at therapeutic doses but risperidone did not.¹³ Researchers believe these features reduce olanzapine’s EPS risk compared with other antipsychotics.

TREATMENT: Drug works, but …

Three weeks after Ms. K’s presentation, we stop all psychotropics, start olanzapine, 10 mg nightly, for psychosis and mania, and continue propranolol, 30 mg bid, for akathisia. Within 2 days, Ms. K’s akathisia improves significantly.

We also start lithium, 150 mg bid, for mania, and increase it 4 days later to 300 mg bid to maintain serum lithium at approximately 1 mEq/L. We check serum lithium every 3 days after dosage adjustment. Although lithium can induce akathisia, we thought it would most effectively control her mania.

Six days after we started the new medications, Ms. K’s mania and psychosis begin to improve and she becomes euthymic. She is able to sit calmly during group therapy and community meetings.

Ten days after we start olanzapine and lithium, Ms. K appears bloated. Weight check shows an approximate 5-lb weight gain since starting the medications, both of which can cause weight gain and other metabolic side effects.

At Ms. K’s request, we stop olanzapine and start aripiprazole, 5 mg/d, to try to control her weight gain. We continue lithium and propranolol, which have been controlling her mood and akathisia. The next day—after 1 dose of aripiprazole—her akathisia returns.

The authors’ observations

Because aripiprazole was started as soon as olanzapine was discontinued, it is unclear which action aggravated Ms. K’s akathisia or if both were to blame.

Akathisia’s underlying cause is uncertain. Researchers believe dopamine receptor blockade in the mesocortical dopamine system might be responsible.³ Positron-emission tomography studies suggest that D2 receptor occupancy in the striatum contributes to akathisia, and noradrenergic and serotonergic systems also play a role.^3,14

 

Antipsychotics, antidepressants, and sympathomimetics all have been implicated in akathisia, but antipsychotics that are potent serotonin (5HT) receptor antagonists—such as olanzapine and clozapine—show a lower incidence compared with other psychotropic agents.³

Aripiprazole—a partial D2 and 5HT1A receptor agonist and 5HT2 receptor antagonist—could have caused Ms. K’s akathisia. In 1 study, 11% of patients receiving aripiprazole, 15 to 30 mg/d, for acute mania reported akathisia symptoms.¹⁵

Olanzapine cessation could have caused Ms. K’s akathisia, although no cases of akathisia secondary to olanzapine withdrawal have been reported. Alternatively, olanzapine could have interacted with lithium to block lithium’s ability to induce akathisia.

TREATMENT: Back to olanzapine

After we thoroughly discuss olanzapine’s risks and benefits with Ms. K, she consents to switch back to olanzapine, 10 mg/d. We also instruct her to exercise daily and strictly control her diet after discharge.

Ms. K’s akathisia improves dramatically within 1 to 2 days, and her psychosis and mania improve gradually. Her persistent delusions and hallucinations are less intense, although she is still concocting grandiose get-rich-quick schemes.

Ten days after this latest dosage change, we discharge Ms. K on olanzapine, 10 mg/d, and lithium, 300 mg bid. She has no akathisia symptoms, and we arrange placement in an adult home where a psychiatrist sees her regularly. Three years later, she has been lost to follow-up.

Related resource

• AkathisiaSupport.org. Online resource offers links to articles describing causes of and treatments for akathisia subtypes. www.akathisiasupport.org.
  

Drug brand names

• Aripiprazole • Abilify
  
• Carbidopa/levodopa • Stalevo, Parcopa
  
• Clonazepam • Klonopin
  
• Clonidine • Catapres
  
• Cyproheptadine • Periactin
  
• Ethosuximide • Zarontin
  
• Lithium • Eskalith, others
  
• Lorazepam • Ativan
  
• Metoclopramide • Reglan
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Reserpine • various
  
• Risperidone • Risperdal
  
• Trihexyphenidyl • Artane
  
• Valproic acid • Depakote
  

Disclosure

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

HISTORY: ‘Bizarre’ days

Ms. K, age 45, is brought to the ER by her brother, who reports she has been acting “bizarre and crazy” for 3 days. He says his sister—who has bipolar I disorder— has had trouble sleeping, is restless, hears voices, and is contemplating suicide. He adds she was discharged from a psychiatric hospital 2 weeks ago after a 3-month stay.

Risperidone, 2 mg nightly, was controlling Ms. K’s mania until this recent episode. According to her brother, she also has developed continuous involuntary leg and arm movements and cannot sit or stand still. When she tries to sleep, her feet sway back and forth in bed for hours.

We admit Ms. K to the psychiatric inpatient unit because of her suicidality and hallucinations. She is restless and agitated during initial evaluation, pacing around the room or rocking her feet while standing or sitting. Her speech is pressured and the “voices” are urging her to kill herself.

Ms. K is dysphoric and severely distraught about her “nervousness” and continuous urges to move. She says she would rather die than live with incessantly “jittery” legs and arms, yet she wants to be discharged and denies that she is mentally ill. She believes decreased sleep is causing her symptoms and requests a “sleeping pill.”

Ms. K was diagnosed with bipolar I disorder in her late 20s. During manic episodes she goes on spending sprees, makes reckless investments, and gambles impulsively. She has long battled euphoric/irritable mood and paranoid delusions, but
she habitually views her medications as useless and stops taking them.

The patient has been hospitalized at least 4 times with severe manic and psychotic symptoms. She does not use illicit drugs and is medically healthy.

The authors’ observations

Ms. K’s involuntary movements suggest akathisia, a common extrapyramidal side effect of antipsychotics and other psychotropics (Table).¹

Akathisia is characterized by strong feelings of inner restlessness that manifest as excessive walking or pacing and difficulty remaining still. Ms. K’s movements met at least 2 of 5 DSM-IV-TR criteria for acute akathisia (Box). ,²

Akathisia is characterized by at least 5 subtypes: ³

• Acute akathisia begins hours or days after starting the offending medication and lasts
• Tardive is similar to acute akathisia but can arise within 3 to 4 months of starting the offending medication and persists for years.
  
• Chronic akathisia lasts ≥3 months and usually has no temporal correlation with antipsychotic initiation or dosage increase.⁴
  
• Withdrawal akathisia begins within 6 weeks of discontinuing a medication or significantly reducing the dosage.
  
• Pseudo akathisia consists of objective symptoms of movement without subjective awareness or distress. This subtype usually is seen in older patients.
  

Patient history is critical to determining akathisia subtype. Ms. K’s sudden onset of manic and movement symptoms and
history of medication nonadherence strongly suggest akathisia secondary to risperidone withdrawal.⁵ Several
cases of akathisia after risperidone cessation have been reported.⁵

We know risperidone is not causing acute akathisia because Ms. K responded well to the medication during her last hospitalization with no adverse effects. Also, her family confirmed that she stopped taking risperidone after her most recent discharge.

Mania also can fuel incessant movement and increase physical activity, but patients often do not realize they have a problem while in a manic phase. Also, swinging and rocking of legs is rarely seen in mania. By contrast, Ms. K was morbidly distraught over her akathisia.

Table

Drugs that can cause akathisia

Dopamine receptor agonists (such as antiparkinsons agents) Carbidopa/levodopa Ethosuximide Metoclopramide Neuroleptics Reserpine Selective serotonin reuptake inhibitors

The authors’ observations

Numerous treatments are available for akathisia:

Beta blockers such as propranolol are most widely used because of their rapid onset of action and overall effectiveness in akathisia.³ Researchers believe these drugs reduce extrapyramidal symptoms (EPS) by blocking the adrenergic system. Propranolol can be used at a maximum 120 mg/d in divided doses.

Beta blockers, however, can cause bradycardia, hypotension, or respiratory distress. Use beta blockers with caution, and monitor for these adverse effects.

Benzodiazepines. Clonazepam, which enhances the inhibitory effect of GABA in the brain, is commonly used for akathisia because of its effectiveness and long elimination half-life³ (30 to 40 hours), which decreases the risk of medication withdrawal.

Patients, however, can develop a tolerance to clonazepam and become addicted to it. Use clonazepam with caution in patients with past substance abuse, and watch for sedation, fatigue,

 

and disinhibition-induced aggression in all patients.

Anticholinergics such as trihexyphenidyl are more commonly used for EPS associated with parkinsonian symptoms or side effects but can be partially effective for akathisia.³ Anticholinergics block the CNS cholinergic activity that causes parkinsonian symptoms.

Cyproheptadine, clonidine, and mianserin have shown some positive results against akathisia in clinical trials.^6-8 Iron, nicotine patches, and amantadine have shown limited effectiveness against akathisia in research studies and case reports.^3,9

Restarting risperidone at a lower dosage—rather than adding a medication— might have resolved Ms. K’s akathisia, but because she was morbidly despondent over her akathisia, we felt we had no time to experiment. We also believed Ms. K’s would respond well to a neuroleptic with a lower EPS risk—such as quetiapine.^1,10

Box

TREATMENT: Trying trials

We perform a complete medical workup to rule out an underlying medical problem. We then start valproic acid, 500 mg bid, for Ms. K’s mania; quetiapine, 50 mg bid, for psychosis and mania; and propranolol, 30 mg bid, for akathisia.

We titrate quetiapine by 100 mg/d every 2 days to 400 mg/d, but after 10 days her akathisia, irritable mood, decreased sleep, and suicidal thoughts persist. We cannot increase propranolol because her blood pressure is 90/60 mm Hg, and adding lorazepam, 0.5 mg tid, does not control her movements. Three days later, we add trihexyphenidyl, 5 mg bid.

Fifteen days after admission, Ms. K remains akathisic, dysphoric, and suicidal despite a 5-drug regimen. Her “nervousness” prevents her from attending groups or other unit activities, and her uncontrollable foot swaying still keeps her awake at night.

The authors’ observations

Neither propranolol, clonazepam, nor trihexyphenidyl alleviated Ms. K’s akathisia. Switching to another neuroleptic with a relatively low EPS risk—such as olanzapine—might help. Olanzapine reduced akathisia in 3 case reports,¹¹ and we hope its strong anticholinergic and antiserotonergic action will help resolve Ms. K’s akathisia.

Patients treated with therapeutic dosages of olanzapine have shown increased muscarinic receptor occupancy compared
with patients receiving therapeutic dosages of risperidone.¹² In another study, olanzapine showed anticholinergic activity at therapeutic doses but risperidone did not.¹³ Researchers believe these features reduce olanzapine’s EPS risk compared with other antipsychotics.

TREATMENT: Drug works, but …

Three weeks after Ms. K’s presentation, we stop all psychotropics, start olanzapine, 10 mg nightly, for psychosis and mania, and continue propranolol, 30 mg bid, for akathisia. Within 2 days, Ms. K’s akathisia improves significantly.

We also start lithium, 150 mg bid, for mania, and increase it 4 days later to 300 mg bid to maintain serum lithium at approximately 1 mEq/L. We check serum lithium every 3 days after dosage adjustment. Although lithium can induce akathisia, we thought it would most effectively control her mania.

Six days after we started the new medications, Ms. K’s mania and psychosis begin to improve and she becomes euthymic. She is able to sit calmly during group therapy and community meetings.

Ten days after we start olanzapine and lithium, Ms. K appears bloated. Weight check shows an approximate 5-lb weight gain since starting the medications, both of which can cause weight gain and other metabolic side effects.

At Ms. K’s request, we stop olanzapine and start aripiprazole, 5 mg/d, to try to control her weight gain. We continue lithium and propranolol, which have been controlling her mood and akathisia. The next day—after 1 dose of aripiprazole—her akathisia returns.

The authors’ observations

Because aripiprazole was started as soon as olanzapine was discontinued, it is unclear which action aggravated Ms. K’s akathisia or if both were to blame.

Akathisia’s underlying cause is uncertain. Researchers believe dopamine receptor blockade in the mesocortical dopamine system might be responsible.³ Positron-emission tomography studies suggest that D2 receptor occupancy in the striatum contributes to akathisia, and noradrenergic and serotonergic systems also play a role.^3,14

 

Antipsychotics, antidepressants, and sympathomimetics all have been implicated in akathisia, but antipsychotics that are potent serotonin (5HT) receptor antagonists—such as olanzapine and clozapine—show a lower incidence compared with other psychotropic agents.³

Aripiprazole—a partial D2 and 5HT1A receptor agonist and 5HT2 receptor antagonist—could have caused Ms. K’s akathisia. In 1 study, 11% of patients receiving aripiprazole, 15 to 30 mg/d, for acute mania reported akathisia symptoms.¹⁵

Olanzapine cessation could have caused Ms. K’s akathisia, although no cases of akathisia secondary to olanzapine withdrawal have been reported. Alternatively, olanzapine could have interacted with lithium to block lithium’s ability to induce akathisia.

TREATMENT: Back to olanzapine

After we thoroughly discuss olanzapine’s risks and benefits with Ms. K, she consents to switch back to olanzapine, 10 mg/d. We also instruct her to exercise daily and strictly control her diet after discharge.

Ms. K’s akathisia improves dramatically within 1 to 2 days, and her psychosis and mania improve gradually. Her persistent delusions and hallucinations are less intense, although she is still concocting grandiose get-rich-quick schemes.

Ten days after this latest dosage change, we discharge Ms. K on olanzapine, 10 mg/d, and lithium, 300 mg bid. She has no akathisia symptoms, and we arrange placement in an adult home where a psychiatrist sees her regularly. Three years later, she has been lost to follow-up.

Related resource

• AkathisiaSupport.org. Online resource offers links to articles describing causes of and treatments for akathisia subtypes. www.akathisiasupport.org.
  

Drug brand names

• Aripiprazole • Abilify
  
• Carbidopa/levodopa • Stalevo, Parcopa
  
• Clonazepam • Klonopin
  
• Clonidine • Catapres
  
• Cyproheptadine • Periactin
  
• Ethosuximide • Zarontin
  
• Lithium • Eskalith, others
  
• Lorazepam • Ativan
  
• Metoclopramide • Reglan
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Reserpine • various
  
• Risperidone • Risperdal
  
• Trihexyphenidyl • Artane
  
• Valproic acid • Depakote
  

Disclosure

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

HISTORY: ‘Bizarre’ days

Ms. K, age 45, is brought to the ER by her brother, who reports she has been acting “bizarre and crazy” for 3 days. He says his sister—who has bipolar I disorder— has had trouble sleeping, is restless, hears voices, and is contemplating suicide. He adds she was discharged from a psychiatric hospital 2 weeks ago after a 3-month stay.

Risperidone, 2 mg nightly, was controlling Ms. K’s mania until this recent episode. According to her brother, she also has developed continuous involuntary leg and arm movements and cannot sit or stand still. When she tries to sleep, her feet sway back and forth in bed for hours.

We admit Ms. K to the psychiatric inpatient unit because of her suicidality and hallucinations. She is restless and agitated during initial evaluation, pacing around the room or rocking her feet while standing or sitting. Her speech is pressured and the “voices” are urging her to kill herself.

Ms. K is dysphoric and severely distraught about her “nervousness” and continuous urges to move. She says she would rather die than live with incessantly “jittery” legs and arms, yet she wants to be discharged and denies that she is mentally ill. She believes decreased sleep is causing her symptoms and requests a “sleeping pill.”

Ms. K was diagnosed with bipolar I disorder in her late 20s. During manic episodes she goes on spending sprees, makes reckless investments, and gambles impulsively. She has long battled euphoric/irritable mood and paranoid delusions, but
she habitually views her medications as useless and stops taking them.

The patient has been hospitalized at least 4 times with severe manic and psychotic symptoms. She does not use illicit drugs and is medically healthy.

The authors’ observations

Ms. K’s involuntary movements suggest akathisia, a common extrapyramidal side effect of antipsychotics and other psychotropics (Table).¹

Akathisia is characterized by strong feelings of inner restlessness that manifest as excessive walking or pacing and difficulty remaining still. Ms. K’s movements met at least 2 of 5 DSM-IV-TR criteria for acute akathisia (Box). ,²

Akathisia is characterized by at least 5 subtypes: ³

• Acute akathisia begins hours or days after starting the offending medication and lasts
• Tardive is similar to acute akathisia but can arise within 3 to 4 months of starting the offending medication and persists for years.
  
• Chronic akathisia lasts ≥3 months and usually has no temporal correlation with antipsychotic initiation or dosage increase.⁴
  
• Withdrawal akathisia begins within 6 weeks of discontinuing a medication or significantly reducing the dosage.
  
• Pseudo akathisia consists of objective symptoms of movement without subjective awareness or distress. This subtype usually is seen in older patients.
  

Patient history is critical to determining akathisia subtype. Ms. K’s sudden onset of manic and movement symptoms and
history of medication nonadherence strongly suggest akathisia secondary to risperidone withdrawal.⁵ Several
cases of akathisia after risperidone cessation have been reported.⁵

We know risperidone is not causing acute akathisia because Ms. K responded well to the medication during her last hospitalization with no adverse effects. Also, her family confirmed that she stopped taking risperidone after her most recent discharge.

Mania also can fuel incessant movement and increase physical activity, but patients often do not realize they have a problem while in a manic phase. Also, swinging and rocking of legs is rarely seen in mania. By contrast, Ms. K was morbidly distraught over her akathisia.

Table

Drugs that can cause akathisia

Dopamine receptor agonists (such as antiparkinsons agents) Carbidopa/levodopa Ethosuximide Metoclopramide Neuroleptics Reserpine Selective serotonin reuptake inhibitors

The authors’ observations

Numerous treatments are available for akathisia:

Beta blockers such as propranolol are most widely used because of their rapid onset of action and overall effectiveness in akathisia.³ Researchers believe these drugs reduce extrapyramidal symptoms (EPS) by blocking the adrenergic system. Propranolol can be used at a maximum 120 mg/d in divided doses.

Beta blockers, however, can cause bradycardia, hypotension, or respiratory distress. Use beta blockers with caution, and monitor for these adverse effects.

Benzodiazepines. Clonazepam, which enhances the inhibitory effect of GABA in the brain, is commonly used for akathisia because of its effectiveness and long elimination half-life³ (30 to 40 hours), which decreases the risk of medication withdrawal.

Patients, however, can develop a tolerance to clonazepam and become addicted to it. Use clonazepam with caution in patients with past substance abuse, and watch for sedation, fatigue,

 

and disinhibition-induced aggression in all patients.

Anticholinergics such as trihexyphenidyl are more commonly used for EPS associated with parkinsonian symptoms or side effects but can be partially effective for akathisia.³ Anticholinergics block the CNS cholinergic activity that causes parkinsonian symptoms.

Cyproheptadine, clonidine, and mianserin have shown some positive results against akathisia in clinical trials.^6-8 Iron, nicotine patches, and amantadine have shown limited effectiveness against akathisia in research studies and case reports.^3,9

Restarting risperidone at a lower dosage—rather than adding a medication— might have resolved Ms. K’s akathisia, but because she was morbidly despondent over her akathisia, we felt we had no time to experiment. We also believed Ms. K’s would respond well to a neuroleptic with a lower EPS risk—such as quetiapine.^1,10

Box

TREATMENT: Trying trials

We perform a complete medical workup to rule out an underlying medical problem. We then start valproic acid, 500 mg bid, for Ms. K’s mania; quetiapine, 50 mg bid, for psychosis and mania; and propranolol, 30 mg bid, for akathisia.

We titrate quetiapine by 100 mg/d every 2 days to 400 mg/d, but after 10 days her akathisia, irritable mood, decreased sleep, and suicidal thoughts persist. We cannot increase propranolol because her blood pressure is 90/60 mm Hg, and adding lorazepam, 0.5 mg tid, does not control her movements. Three days later, we add trihexyphenidyl, 5 mg bid.

Fifteen days after admission, Ms. K remains akathisic, dysphoric, and suicidal despite a 5-drug regimen. Her “nervousness” prevents her from attending groups or other unit activities, and her uncontrollable foot swaying still keeps her awake at night.

The authors’ observations

Neither propranolol, clonazepam, nor trihexyphenidyl alleviated Ms. K’s akathisia. Switching to another neuroleptic with a relatively low EPS risk—such as olanzapine—might help. Olanzapine reduced akathisia in 3 case reports,¹¹ and we hope its strong anticholinergic and antiserotonergic action will help resolve Ms. K’s akathisia.

Patients treated with therapeutic dosages of olanzapine have shown increased muscarinic receptor occupancy compared
with patients receiving therapeutic dosages of risperidone.¹² In another study, olanzapine showed anticholinergic activity at therapeutic doses but risperidone did not.¹³ Researchers believe these features reduce olanzapine’s EPS risk compared with other antipsychotics.

TREATMENT: Drug works, but …

Three weeks after Ms. K’s presentation, we stop all psychotropics, start olanzapine, 10 mg nightly, for psychosis and mania, and continue propranolol, 30 mg bid, for akathisia. Within 2 days, Ms. K’s akathisia improves significantly.

We also start lithium, 150 mg bid, for mania, and increase it 4 days later to 300 mg bid to maintain serum lithium at approximately 1 mEq/L. We check serum lithium every 3 days after dosage adjustment. Although lithium can induce akathisia, we thought it would most effectively control her mania.

Six days after we started the new medications, Ms. K’s mania and psychosis begin to improve and she becomes euthymic. She is able to sit calmly during group therapy and community meetings.

Ten days after we start olanzapine and lithium, Ms. K appears bloated. Weight check shows an approximate 5-lb weight gain since starting the medications, both of which can cause weight gain and other metabolic side effects.

At Ms. K’s request, we stop olanzapine and start aripiprazole, 5 mg/d, to try to control her weight gain. We continue lithium and propranolol, which have been controlling her mood and akathisia. The next day—after 1 dose of aripiprazole—her akathisia returns.

The authors’ observations

Because aripiprazole was started as soon as olanzapine was discontinued, it is unclear which action aggravated Ms. K’s akathisia or if both were to blame.

Akathisia’s underlying cause is uncertain. Researchers believe dopamine receptor blockade in the mesocortical dopamine system might be responsible.³ Positron-emission tomography studies suggest that D2 receptor occupancy in the striatum contributes to akathisia, and noradrenergic and serotonergic systems also play a role.^3,14

 

Antipsychotics, antidepressants, and sympathomimetics all have been implicated in akathisia, but antipsychotics that are potent serotonin (5HT) receptor antagonists—such as olanzapine and clozapine—show a lower incidence compared with other psychotropic agents.³

Aripiprazole—a partial D2 and 5HT1A receptor agonist and 5HT2 receptor antagonist—could have caused Ms. K’s akathisia. In 1 study, 11% of patients receiving aripiprazole, 15 to 30 mg/d, for acute mania reported akathisia symptoms.¹⁵

Olanzapine cessation could have caused Ms. K’s akathisia, although no cases of akathisia secondary to olanzapine withdrawal have been reported. Alternatively, olanzapine could have interacted with lithium to block lithium’s ability to induce akathisia.

TREATMENT: Back to olanzapine

After we thoroughly discuss olanzapine’s risks and benefits with Ms. K, she consents to switch back to olanzapine, 10 mg/d. We also instruct her to exercise daily and strictly control her diet after discharge.

Ms. K’s akathisia improves dramatically within 1 to 2 days, and her psychosis and mania improve gradually. Her persistent delusions and hallucinations are less intense, although she is still concocting grandiose get-rich-quick schemes.

Ten days after this latest dosage change, we discharge Ms. K on olanzapine, 10 mg/d, and lithium, 300 mg bid. She has no akathisia symptoms, and we arrange placement in an adult home where a psychiatrist sees her regularly. Three years later, she has been lost to follow-up.

Related resource

• AkathisiaSupport.org. Online resource offers links to articles describing causes of and treatments for akathisia subtypes. www.akathisiasupport.org.
  

Drug brand names

• Aripiprazole • Abilify
  
• Carbidopa/levodopa • Stalevo, Parcopa
  
• Clonazepam • Klonopin
  
• Clonidine • Catapres
  
• Cyproheptadine • Periactin
  
• Ethosuximide • Zarontin
  
• Lithium • Eskalith, others
  
• Lorazepam • Ativan
  
• Metoclopramide • Reglan
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Reserpine • various
  
• Risperidone • Risperdal
  
• Trihexyphenidyl • Artane
  
• Valproic acid • Depakote
  

Disclosure

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

Case: You’re a ‘freak’

A local mental health agency refers Mr. Z, age 23, to our inpatient psychiatry service because of increasing suicidality and psychosis. He began receiving care from the mental health agency 3 years ago, after a psychiatrist diagnosed paranoid schizophrenia.

At presentation, Mr. Z is delusionally preoccupied with a brief relationship he had with a young woman at college 2 years ago. He feels embarrassed about his conduct toward her during a psychotic episode and her subsequent response. He believes strangers are ridiculing him, and he hears voices calling him a “freak” and making crude references to the encounter. He is also contemplating suicide and endorses a suicide plan.

Mr. Z was hospitalized for 1 month last year with schizophrenia symptoms. He is medically healthy and does not abuse alcohol or drugs.

We admit Mr. Z because of his suicidality. Four weeks later, he remains suicidal and hears voices telling him to “rape” and “kill.” Successive 2-week trials of risperidone, 1 mg/d titrated to 5 mg/d, and quetiapine, 200 mg/d titrated to 700 mg/d, cause intolerable akathisia. We try adding propranolol, 20 mg every 8 hours, to alleviate akathisia, but to no avail. Previous trials of olanzapine, 30 mg/d, and haloperidol, dosage unknown, were unsuccessful or caused akathisia.

The authors’ observations

Substantial evidence supports clozapine’s efficacy in treatment-resistant schizophrenia, and this second-generation antipsychotic (SGA) also might reduce suicidality.^1,2 Clinicians often combine antipsychotics, switch to an antidepressant, or add a mood stabilizer for treatment-resistant schizophrenia,³ but little evidence supports these options.

Mr. Z had failed at least 4 antipsychotic trials. We consider clozapine for patients with severe psychosis who have failed 2 or 3 antipsychotic trials or cannot tolerate these medications. Severity of psychosis and presence of suicidality warrant use of clozapine in treatment-resistant cases.

If Mr. Z had tolerated risperidone or quetiapine, we would have waited as long as 8 weeks before switching to clozapine. In inpatients, improvement should be seen 2 to 4 weeks after starting an antipsychotic.

Thoroughly discuss clozapine’s risks and benefits with the patient and caregiver(s) before prescribing. Clozapine can cause a range of side effects, including sedation, weight gain, sialorrhea, seizures, diabetes, pulmonary emboli, and—most notoriously—agranulocytosis. These effects can occur anytime, but the risk is especially high within 1 year of starting the medication.⁴

Perform blood tests weekly during the first 6 months of clozapine therapy and bi-weekly thereafter to check for abnormally low white blood cell counts that might suggest agranulocytosis.

Box 1

TREATMENT: New regimen

After discussing clozapine’s risks and benefits with Mr. Z and his parents, we start the medication at 25 mg/d to gauge tolerability, then titrate to 300 mg/d over 10 days. Mr. Z tolerates clozapine well, with some sedation and sialorrhea. A blood test taken 7 days after we start clozapine shows a normal white blood cell count.

After 10 days on clozapine, Mr. Z’s delusions and hallucinations are considerably less intense. He is no longer suicidal and visits his former college with his parents without thinking about his past acquaintance. We discharge him on clozapine, 300 mg/d, and refer him to the local mental health agency.

Two days later, Mr. Z’s parents report that since discharge their son has had extreme fatigue, shortness of breath, leg edema, and chest pain. We advise them to immediately take their son to the ER for cardiac workup.

 

The authors’ observations

Mr. Z’s sudden-onset physical symptoms suggest myocarditis, a rare but potentially fatal side effect of clozapine whose specific cause is unclear (Box 1).^5-14 Myocarditis has been reported in 0.02% to 0.18% of patients exposed to clozapine,^15-18 with incidence as high as 1.3% per 235 patients.¹⁹

Affected patients typically have been taking clozapine at therapeutic dosages (100 to 450 mg/d).⁷ Clozapine use is most prevalent among men ages 20 to 40, who tend to have more severe schizophrenia and lower cardiac risk than other populations. Correspondingly, clozapine-induced myocarditis is most prevalent in younger men,²⁰ although what specifically causes this susceptibility is unknown.

Nonspecific symptoms such as dyspnea, tachycardia, chest pain, or fever can signal myocarditis (Table)^7,21 and can surface within 4 to 8 weeks of starting clozapine.²² Haas et al²⁰ reported other symptoms—such as leukocytosis—in young (median age 30), predominantly male patients with clozapine-induced myocarditis. Symptoms that typically occur during clozapine titration—such as fever and tachycardia—can mask “subclinical” myocarditis.²²

Mr. Z’s nonspecific symptoms could signal clozapine-induced agranulocytosis or a viral syndrome, or could be delusional. The patient’s acute, sudden symptom onset strongly suggests a cardiac cause. Also, his delusions subsided, and normal blood readings helped us rule out agranulocytosis.

Coulter et al²³ associated myocarditis and cardiomyopathy, a noninflammatory heart muscle disease, with several antipsychotics—including clozapine, chlorpromazine, fluphenazine, haloperidol, and risperidone—as well as lithium. More research is needed to confirm this association.

Emergency medical intervention is critical because mortality rates for myocarditis induced by clozapine have been estimated at 50%.²⁰ Myocarditis could progress to dilated cardiomyopathy,²⁴ with similarly high mortality rates across 5 years.⁷

Order a cardiology consult and workup including:

• serum electrolytes
  
• complete blood count
  
• ECG²¹
  
• tests for myocardial damage including creatine kinase with MB fractionation (CK-MB) and testing for serum troponin I,²⁵ lactic dehydrogenase, and aspartate transaminase (SGOT)²¹
  
• assessment for immune activation and peripheral eosinophilia.²⁵
  

Findings on ECG are wide-ranging and might include sinus tachycardia, atrial or ventricular arrhythmias, left ventricular hypertrophy, nonspecific ST segment and T-wave abnormalities, and intraventricular conduction defects. Assess cardiac function with echocardiography to monitor for dilated cardiomyopathy. Stop clozapine immediately if findings suggest myocarditis.¹⁹

Table

Symptoms that could signal myocarditis in patients taking clozapine

Chest pain Confusion/mental status changes Dyspnea Edema Fatigue/weakness Fever Prolonged tachycardia
Source: Reference 7

TESTING: ‘Is this necessary?’

We contact the ER physician to request the above-mentioned tests, but he questions the need for such extensive and costly testing in a psychiatric patient with nonspecific symptoms.

After several phone conversations to review our recommendations, the emergency physician suggests sending Mr. Z home on a watch-and-wait protocol. We politely but firmly emphasize that Mr. Z needs a full cardiac workup, after which the physician consents to the tests (Box 2).

FINDINGS: suspicious readings

Mr. Z’s cardiac imaging results suggest a cardiopathy:

• echocardiogram shows mild ventricular enlargement with a decreased ejection fraction of 45% (normal reading, 55% to 60%)
  
• ECG shows normal sinus rhythm with low-voltage diffuse T-wave flattening throughout all leads without ST elevation
  
• creatine phosphokinase (CPK) and CKMB are within normal ranges
  
• troponin I is 0.33 ng/mL, a high-normal reading.
  

Mr. Z had no past cardiac abnormality, but an aunt had died in her 30s of viral myocarditis.

Based on these readings, the cardiology service admits Mr. Z with a presumptive diagnosis of clozapine-induced cardiomyopathy. The attending cardiologist stops clozapine and starts the angiotensin-converting enzyme inhibitor enalapril, 2.5 mg bid, for ventricular remodeling. Medical workup includes cytologic testing to rule out immunologic or viral disease.

Five days later, Mr. Z’s cardiac symptoms have resolved. The cardiology unit discharges him on enalapril, 2.5 mg bid, and schedules a cardiac ultrasound for 2 weeks after discharge to confirm progress.

The authors’ observations

Maintain high clinical suspicion while using clozapine. Similar to other patients with a clozapine-induced cardiopathy,¹⁶ Mr. Z showed rapid symptomatic changes after a benign initial course and experienced fairly vague symptoms that raised limited clinical concern at first.

Before starting clozapine therapy, screen all patients for pre-existing cardiac disease, which contraindicates this medication. Alert patients and caregivers to the risks and symptoms that require close monitoring early in treatment.

Many researchers suggest monitoring for myocarditis during the first month of therapy and ordering ECG at baseline and 2 and 4 weeks after starting clozapine.^21,22 Berk et al²⁶ suggest more aggressive monitoring, including:

• baseline ECG
  
• transthoracic echocardiogram
  
• baseline troponin/CK-MB
  
• ECG and troponin/CK-MB at 7 and 14 days
  
• echocardiogram at 6 and 12 months and then annually.
  

RELAPSE: Return of the ‘freak’

 

Immediately after Mr. Z’s discharge from the cardiology unit, we readmit him to inpatient psychiatry. His parents and case manager say he is again becoming preoccupied with his brief college relationship. He has been off clozapine for 5 days.

The authors’ observations

The American Psychiatric Association²⁷ (see http://www.psych.org/psych_pract/treatg/pg/SchizPG-Complete-Feb04.pdf) recommends maximizing 1 medication for at least 2 to 4 weeks to assess schizophrenia symptom response and urges clinicians to consider adverse effects, medical comorbidities, and patient preference before continuing the medication.

These recommendations highlight the challenges of treating medication-resistant schizophrenia. Relapse is common after a serious reaction to clozapine, and combining 2 or more other antipsychotics could lead to significantly greater side effects. A time-limited trial with an antipsychotic and an adjunctive agent might be attempted while carefully weighing the combination’s risks and benefits.²⁷

Clozapine reduced Mr. Z’s psychosis, but rechallenge would likely cause his potentially fatal cardiomyopathy to re-emerge. His sensitivity to adverse antipsychotic effects discourages polypharmacy and further complicates our decision.

Because our therapeutic options are limited, we consider an agent chemically similar to clozapine with pharmacologic overlap—such as olanzapine,⁶ which had improved Mr. Z’s psychotic symptoms during his hospitalization 1 year ago but caused akathisia. We hope to avoid this adverse effect by limiting the dosage to 30 mg/d and adding the antidepressant bupropion, which Mr. Z says had helped him previously.

Box 2

TREATMENT: Another trial

We start olanzapine, 5 mg/d, and titrate to 20 mg/d over 1 week. We add sustained-release bupropion, 200 mg bid, for associated dysphoria.

Mr. Z’s symptoms and paranoia gradually decline, and he tolerates off-unit passes with friends and family before discharge. Staff works closely with him to develop cognitive-behavioral strategies to manage residual paranoia and hallucinations, such as assessing evidence for his delusional beliefs and developing tools to distract him from remaining “voices.” He reports no cardiac symptoms and continues taking enalapril, 2.5 mg bid.

We discharge Mr. Z after 1 week, at which point he shows no suicidal or homicidal thoughts. Follow-up echocardiogram 2 weeks later shows ejection fraction has improved to 60%, suggesting absence of cardiomyopathy.

When last contacted 3 months ago, Mr. Z was stable and living with his parents. He was continuing outpatient psychiatric care and hoped to find an apartment and transition to independent living.

Related resource

• Clozapine safety information.
  www.clozaril.com/.
  

Drug brand names

• Bupropion • Wellbutrin
  
• Chlorpromazine • Thorazine
  
• Clozapine • Clozaril
  
• Enalapril • Vasotec
  
• Fluphenazine • Prolixin, Permitil
  
• Haloperidol • Haldol
  
• Lithium • Eskalith, others
  
• Olanzapine • Zyprexa
  
• Propranolol • Inderal
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  

Disclosure

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