Case-Based Review

History: a ‘negative’ view

Mr. J, a 50-year-old native of Fiji, has had depression and substance abuse disorder for more than 10 years, marked by irritability, poor sleep, hopelessness, and suicidality. He also suffered a traumatic brain injury in the military 25 years ago.

Police bring Mr. J to the ER after they find him wandering near traffic and speaking incoherently. His feet and hands jerk on the way to the hospital, leading police to suspect that Mr. J has suffered a grand mal seizure.

In the ER, Mr. J appears confused, has visual hallucinations, and moves his hands and feet involuntarily. His head and arms move erratically during the ER psychiatrist’s interview, and he says that his pelvis is arching forward and preventing him from walking steadily. The day before, he says, he saw frightening “visions” of a being who looked “like a photo negative.”

Mr. J has been seeing an outpatient psychiatrist, who has prescribed citalopram, 40 mg/d, for depression and clonazepam, 1 mg three times daily, for related anxiety symptoms.

The patient is disoriented and inattentive during the mental status examination. His cognitive deficits fluctuate in severity; at times he is aware of his surroundings, then suddenly loses this awareness.

Vital signs are stable. Physical exam shows Mr. J is approximately 30 lb underweight (97 lb) with a body mass index of 16.9 kg/m²—nearly 2 kg/m² below normal. He says he has been skipping meals because of poor appetite. He also has strikingly lizard-like, scaly skin.

Urine drug screen shows no signs of recent alcohol or substance abuse. Complete metabolic profile shows elevated liver enzymes, suggesting alcohol or illicit substance toxicity, medication toxicity, hepatitis, thyroid disorder, muscle disease, or a rare liver condition. EEG shows mild encephalopathy but no ictal activity.

poll here

The authors’ observations

Our psychiatric differential diagnosis is broad:

• visual and auditory hallucinations are concurrent in numerous disorders, including schizophrenia and depression
  
• visual hallucinations alone suggest dementia, delirium, or psychosis resulting from a medical condition, medication, or substance(s) of abuse¹
  
• Mr. J’s past head injury increases his risk of dementia and delirium
  
• his abrupt symptom onset and inattention suggest delirium.
  

Choreoathetosis can result from:

• medications such as stimulants and levodopa
  
• toxins
  
• systemic diseases such as systemic lupus erythematosus, thyrotoxicosis, or stroke
  
• degenerative brain diseases such as Huntington’s disease
  
• or focal brain diseases such as tumors.²
  

Although the test results narrow the differential diagnosis, we still have to consider numerous medical conditions that can cause delirium, such as trauma, cerebral vascular accident, intracerebral masses, CNS infection, and inflammatory disease.

poll here

History: collateral contributions

We refer Mr. J for lumbar puncture to rule out CNS infection and MRI to rule out tumor, abscess, or other structural brain abnormalities that could cause seizure. Results are unremarkable.

We then speak with Mr. J’s outpatient psychiatrist, who reports that Mr. J has had no residual cognitive impairment from his head injury. She adds, though, that he often develops cognitive problems after consuming large amounts of a traditional South Pacific beverage containing kava (Piper methysticum). She explains that Mr. J socializes with fellow Fijians who drink kava at gatherings, and that he often drinks kava to excess. She attributes his dry, scaly skin to excessive kava use.

Upon questioning, Mr. J says he consumes about a half-pound of kava root per day. He says he uses the root to make a tea-like beverage that, like alcohol, induces euphoria and relaxation. He says he began doing this in his youth back in Fiji, and now drinks “many cups” of kava per day.

Mr. J states that his current episode of strange movements and visual hallucinations began hours after he drank several cups of kava the day before police brought him to the ER. He considers his new psychiatric symptoms Jesus’ punishment for drinking kava.

The authors’ observations

Mr. J’s persecutory delusions suggest that he does not fully associate his symptoms with excessive kava use, but his abnormal movements, weight loss, skin changes, liver function abnormalities, and mental status changes are known adverse effects of kava.³ We diagnose substance-induced delirium rather than substance intoxication or substance-induced psychosis because:

• Mr. J’s cognitive symptoms are more severe than those caused by kava intoxication
  
• his psychotic symptoms occur only when he is delirious
  
• his disturbed consciousness, cognitive, and perceptual disturbances and the temporal relationship between symptom onset and massive kava use match DSM-IV-TR criteria for substance-induced delirium.⁴
  

Being aware of cultural customs and beliefs in your practice area can alert you to herbal substance use in various populations, such as kava by patients from the South Pacific or echinacea, goldenseal, and burdock by some Native Americans (see Related resources).

Medicinal use. Patients often use kava and other herbal supplements—including fatty acids, ginkgo biloba, ginseng, St. John’s wort, valerian, and others—with or instead of prescription drugs to alleviate psychiatric symptoms. Complementary and alternative medicine practitioners use kava to treat anxiety, for example (Box).

Anxiety and depression are among the most common reasons persons seek complementary or alternative treatment. In a national survey, 57% of respondents who suffered “anxiety attacks” and 54% of those with “severe depression” reported using such therapies.⁸ Nearly 1 in 5 persons who take prescription drugs also take herbs and/or high-dose vitamin supplements.⁹

Herbal products have been shown to cause adverse effects (Table 1).¹⁰ Kava, for example, has been associated with hepatotoxicity, dermopathy, movement disorders, GI disturbance, and weight loss. Standardized extracts such as capsules and tinctures appear more likely to cause adverse effects than traditional extractions, such as a beverage made by infusing kava root.⁵

Kava toxicity has been reported among heavy users. Although the dosage at which kava becomes dangerous is unknown, the FDA recommends that users not exceed typical dosages (50 to 280 mg/d) and use kava only under a physician’s supervision.¹¹

Also, interactions between herbal products and allopathic medications can cause substantial morbidity (Table 2). St. John’s wort, for example, can lead to serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs)¹² and can reduce blood levels of psychotropics metabolized by the cytochrome P-450 3A4 isoenzyme, such as alprazolam and carbamazepine.

Mr. J combined kava with clonazepam. Both substances affect gamma-aminobutyric (GABA) receptors, increasing the risk of sedation by depressing the CNS.

Table 1

Possible adverse effects of herbal supplements
used for psychiatric symptoms

Potential adverse interactions between psychotropics and complementary/alternative medications

Ask about alternative medicine use

According to a national survey,¹³ many patients do not tell allopathic physicians they are using complementary or alternative medications because:

• “It wasn’t important for the doctor to know.”
  
• “The doctor never asked.”
  
• “It was none of the doctor’s business.”
  
• “The doctor would not understand.”
  
• or “The doctor would disapprove or discourage CAM use.”
  

• routinely question patients about use of alternative therapies
  
• discuss safety and efficacy of commonly used alternative treatments
  
• discuss merits of alternative treatments
  
• provide information on the effectiveness and risks of various treatments
  
• learn about alternative therapies by consulting the Physicians’ Desk Reference (PDR) for Herbal Medicines or similar references
  
• help patients make decisions about alternative treatments, such as finding a qualified, licensed alternative provider.
  

Treatment: quick resolution

We admit Mr. J to the inpatient psychiatry unit. There, we continue his outpatient prescription medications at the same dosages and block access to nonprescription substances. His symptoms begin to improve during the first day of hospitalization. His choreoathetosis, hallucinations, and confusion resolve within 48 hours, and he is medically stable.

We discharge Mr. J after 2 days and continue citalopram and clonazepam at the same dosages.

The authors’ observations

Kava reaches peak plasma levels 1.8 hours after oral dosing and has a short (9-hour) elimination half-life. As a result, kava intoxication symptoms tend to resolve rapidly, as in Mr. J’s case.

Although Mr. J is medically stable, liver damage associated with kava use can be irreversible, prompting some European countries to ban its sale. Make sure patients who report kava use are aware of its hepatotoxicity risk.

Follow-up: kicking the kava habit

Two weeks after Mr. J’s discharge, his psychiatrist notes that his mental status has returned to baseline and that his skin has improved dramatically. The patient is following his citalopram and clonazepam regimen, and he seems more aware of kava’s potential adverse effects.

Mr. J reports that he has not consumed kava since his hospitalization. He has been eating four meals per day and has gained 9 lb. He is pleased with his improved appetite and is motivated to continue abstaining from kava.

Related resources

• National Center for Complementary and Alternative Medicine. http://nccam.nih.gov.
  
• Physicians Desk Reference (PDR) for herbal medicines, 3rd ed. Montvale, NJ: Thomson PDR; 2004.
  
• Ernst E, Pittler MH, Stevinson C, et al. The desktop guide to complementary and alternative medicine. Edinburgh, UK: Mosby; 2001.
  

• Alprazolam • Xanax
  
• Buspirone • BuSpar
  
• Carbamazepine • Equetro, others
  
• Carbidopa • Lodosyn
  
• Citalopram • Celexa
  
• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Trazodone • Desyrel
  

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

History: a ‘negative’ view

Mr. J, a 50-year-old native of Fiji, has had depression and substance abuse disorder for more than 10 years, marked by irritability, poor sleep, hopelessness, and suicidality. He also suffered a traumatic brain injury in the military 25 years ago.

Police bring Mr. J to the ER after they find him wandering near traffic and speaking incoherently. His feet and hands jerk on the way to the hospital, leading police to suspect that Mr. J has suffered a grand mal seizure.

In the ER, Mr. J appears confused, has visual hallucinations, and moves his hands and feet involuntarily. His head and arms move erratically during the ER psychiatrist’s interview, and he says that his pelvis is arching forward and preventing him from walking steadily. The day before, he says, he saw frightening “visions” of a being who looked “like a photo negative.”

Mr. J has been seeing an outpatient psychiatrist, who has prescribed citalopram, 40 mg/d, for depression and clonazepam, 1 mg three times daily, for related anxiety symptoms.

The patient is disoriented and inattentive during the mental status examination. His cognitive deficits fluctuate in severity; at times he is aware of his surroundings, then suddenly loses this awareness.

Vital signs are stable. Physical exam shows Mr. J is approximately 30 lb underweight (97 lb) with a body mass index of 16.9 kg/m²—nearly 2 kg/m² below normal. He says he has been skipping meals because of poor appetite. He also has strikingly lizard-like, scaly skin.

Urine drug screen shows no signs of recent alcohol or substance abuse. Complete metabolic profile shows elevated liver enzymes, suggesting alcohol or illicit substance toxicity, medication toxicity, hepatitis, thyroid disorder, muscle disease, or a rare liver condition. EEG shows mild encephalopathy but no ictal activity.

poll here

The authors’ observations

Our psychiatric differential diagnosis is broad:

• visual and auditory hallucinations are concurrent in numerous disorders, including schizophrenia and depression
  
• visual hallucinations alone suggest dementia, delirium, or psychosis resulting from a medical condition, medication, or substance(s) of abuse¹
  
• Mr. J’s past head injury increases his risk of dementia and delirium
  
• his abrupt symptom onset and inattention suggest delirium.
  

Choreoathetosis can result from:

• medications such as stimulants and levodopa
  
• toxins
  
• systemic diseases such as systemic lupus erythematosus, thyrotoxicosis, or stroke
  
• degenerative brain diseases such as Huntington’s disease
  
• or focal brain diseases such as tumors.²
  

Although the test results narrow the differential diagnosis, we still have to consider numerous medical conditions that can cause delirium, such as trauma, cerebral vascular accident, intracerebral masses, CNS infection, and inflammatory disease.

poll here

History: collateral contributions

We refer Mr. J for lumbar puncture to rule out CNS infection and MRI to rule out tumor, abscess, or other structural brain abnormalities that could cause seizure. Results are unremarkable.

We then speak with Mr. J’s outpatient psychiatrist, who reports that Mr. J has had no residual cognitive impairment from his head injury. She adds, though, that he often develops cognitive problems after consuming large amounts of a traditional South Pacific beverage containing kava (Piper methysticum). She explains that Mr. J socializes with fellow Fijians who drink kava at gatherings, and that he often drinks kava to excess. She attributes his dry, scaly skin to excessive kava use.

Upon questioning, Mr. J says he consumes about a half-pound of kava root per day. He says he uses the root to make a tea-like beverage that, like alcohol, induces euphoria and relaxation. He says he began doing this in his youth back in Fiji, and now drinks “many cups” of kava per day.

Mr. J states that his current episode of strange movements and visual hallucinations began hours after he drank several cups of kava the day before police brought him to the ER. He considers his new psychiatric symptoms Jesus’ punishment for drinking kava.

The authors’ observations

Mr. J’s persecutory delusions suggest that he does not fully associate his symptoms with excessive kava use, but his abnormal movements, weight loss, skin changes, liver function abnormalities, and mental status changes are known adverse effects of kava.³ We diagnose substance-induced delirium rather than substance intoxication or substance-induced psychosis because:

• Mr. J’s cognitive symptoms are more severe than those caused by kava intoxication
  
• his psychotic symptoms occur only when he is delirious
  
• his disturbed consciousness, cognitive, and perceptual disturbances and the temporal relationship between symptom onset and massive kava use match DSM-IV-TR criteria for substance-induced delirium.⁴
  

Being aware of cultural customs and beliefs in your practice area can alert you to herbal substance use in various populations, such as kava by patients from the South Pacific or echinacea, goldenseal, and burdock by some Native Americans (see Related resources).

Medicinal use. Patients often use kava and other herbal supplements—including fatty acids, ginkgo biloba, ginseng, St. John’s wort, valerian, and others—with or instead of prescription drugs to alleviate psychiatric symptoms. Complementary and alternative medicine practitioners use kava to treat anxiety, for example (Box).

Anxiety and depression are among the most common reasons persons seek complementary or alternative treatment. In a national survey, 57% of respondents who suffered “anxiety attacks” and 54% of those with “severe depression” reported using such therapies.⁸ Nearly 1 in 5 persons who take prescription drugs also take herbs and/or high-dose vitamin supplements.⁹

Herbal products have been shown to cause adverse effects (Table 1).¹⁰ Kava, for example, has been associated with hepatotoxicity, dermopathy, movement disorders, GI disturbance, and weight loss. Standardized extracts such as capsules and tinctures appear more likely to cause adverse effects than traditional extractions, such as a beverage made by infusing kava root.⁵

Kava toxicity has been reported among heavy users. Although the dosage at which kava becomes dangerous is unknown, the FDA recommends that users not exceed typical dosages (50 to 280 mg/d) and use kava only under a physician’s supervision.¹¹

Also, interactions between herbal products and allopathic medications can cause substantial morbidity (Table 2). St. John’s wort, for example, can lead to serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs)¹² and can reduce blood levels of psychotropics metabolized by the cytochrome P-450 3A4 isoenzyme, such as alprazolam and carbamazepine.

Mr. J combined kava with clonazepam. Both substances affect gamma-aminobutyric (GABA) receptors, increasing the risk of sedation by depressing the CNS.

Table 1

Possible adverse effects of herbal supplements
used for psychiatric symptoms

Potential adverse interactions between psychotropics and complementary/alternative medications

Ask about alternative medicine use

According to a national survey,¹³ many patients do not tell allopathic physicians they are using complementary or alternative medications because:

• “It wasn’t important for the doctor to know.”
  
• “The doctor never asked.”
  
• “It was none of the doctor’s business.”
  
• “The doctor would not understand.”
  
• or “The doctor would disapprove or discourage CAM use.”
  

• routinely question patients about use of alternative therapies
  
• discuss safety and efficacy of commonly used alternative treatments
  
• discuss merits of alternative treatments
  
• provide information on the effectiveness and risks of various treatments
  
• learn about alternative therapies by consulting the Physicians’ Desk Reference (PDR) for Herbal Medicines or similar references
  
• help patients make decisions about alternative treatments, such as finding a qualified, licensed alternative provider.
  

Treatment: quick resolution

We admit Mr. J to the inpatient psychiatry unit. There, we continue his outpatient prescription medications at the same dosages and block access to nonprescription substances. His symptoms begin to improve during the first day of hospitalization. His choreoathetosis, hallucinations, and confusion resolve within 48 hours, and he is medically stable.

We discharge Mr. J after 2 days and continue citalopram and clonazepam at the same dosages.

The authors’ observations

Kava reaches peak plasma levels 1.8 hours after oral dosing and has a short (9-hour) elimination half-life. As a result, kava intoxication symptoms tend to resolve rapidly, as in Mr. J’s case.

Although Mr. J is medically stable, liver damage associated with kava use can be irreversible, prompting some European countries to ban its sale. Make sure patients who report kava use are aware of its hepatotoxicity risk.

Follow-up: kicking the kava habit

Two weeks after Mr. J’s discharge, his psychiatrist notes that his mental status has returned to baseline and that his skin has improved dramatically. The patient is following his citalopram and clonazepam regimen, and he seems more aware of kava’s potential adverse effects.

Mr. J reports that he has not consumed kava since his hospitalization. He has been eating four meals per day and has gained 9 lb. He is pleased with his improved appetite and is motivated to continue abstaining from kava.

Related resources

• National Center for Complementary and Alternative Medicine. http://nccam.nih.gov.
  
• Physicians Desk Reference (PDR) for herbal medicines, 3rd ed. Montvale, NJ: Thomson PDR; 2004.
  
• Ernst E, Pittler MH, Stevinson C, et al. The desktop guide to complementary and alternative medicine. Edinburgh, UK: Mosby; 2001.
  

• Alprazolam • Xanax
  
• Buspirone • BuSpar
  
• Carbamazepine • Equetro, others
  
• Carbidopa • Lodosyn
  
• Citalopram • Celexa
  
• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Trazodone • Desyrel
  

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

History: a ‘negative’ view

Mr. J, a 50-year-old native of Fiji, has had depression and substance abuse disorder for more than 10 years, marked by irritability, poor sleep, hopelessness, and suicidality. He also suffered a traumatic brain injury in the military 25 years ago.

Police bring Mr. J to the ER after they find him wandering near traffic and speaking incoherently. His feet and hands jerk on the way to the hospital, leading police to suspect that Mr. J has suffered a grand mal seizure.

In the ER, Mr. J appears confused, has visual hallucinations, and moves his hands and feet involuntarily. His head and arms move erratically during the ER psychiatrist’s interview, and he says that his pelvis is arching forward and preventing him from walking steadily. The day before, he says, he saw frightening “visions” of a being who looked “like a photo negative.”

Mr. J has been seeing an outpatient psychiatrist, who has prescribed citalopram, 40 mg/d, for depression and clonazepam, 1 mg three times daily, for related anxiety symptoms.

The patient is disoriented and inattentive during the mental status examination. His cognitive deficits fluctuate in severity; at times he is aware of his surroundings, then suddenly loses this awareness.

Vital signs are stable. Physical exam shows Mr. J is approximately 30 lb underweight (97 lb) with a body mass index of 16.9 kg/m²—nearly 2 kg/m² below normal. He says he has been skipping meals because of poor appetite. He also has strikingly lizard-like, scaly skin.

Urine drug screen shows no signs of recent alcohol or substance abuse. Complete metabolic profile shows elevated liver enzymes, suggesting alcohol or illicit substance toxicity, medication toxicity, hepatitis, thyroid disorder, muscle disease, or a rare liver condition. EEG shows mild encephalopathy but no ictal activity.

poll here

The authors’ observations

Our psychiatric differential diagnosis is broad:

• visual and auditory hallucinations are concurrent in numerous disorders, including schizophrenia and depression
  
• visual hallucinations alone suggest dementia, delirium, or psychosis resulting from a medical condition, medication, or substance(s) of abuse¹
  
• Mr. J’s past head injury increases his risk of dementia and delirium
  
• his abrupt symptom onset and inattention suggest delirium.
  

Choreoathetosis can result from:

• medications such as stimulants and levodopa
  
• toxins
  
• systemic diseases such as systemic lupus erythematosus, thyrotoxicosis, or stroke
  
• degenerative brain diseases such as Huntington’s disease
  
• or focal brain diseases such as tumors.²
  

Although the test results narrow the differential diagnosis, we still have to consider numerous medical conditions that can cause delirium, such as trauma, cerebral vascular accident, intracerebral masses, CNS infection, and inflammatory disease.

poll here

History: collateral contributions

We refer Mr. J for lumbar puncture to rule out CNS infection and MRI to rule out tumor, abscess, or other structural brain abnormalities that could cause seizure. Results are unremarkable.

We then speak with Mr. J’s outpatient psychiatrist, who reports that Mr. J has had no residual cognitive impairment from his head injury. She adds, though, that he often develops cognitive problems after consuming large amounts of a traditional South Pacific beverage containing kava (Piper methysticum). She explains that Mr. J socializes with fellow Fijians who drink kava at gatherings, and that he often drinks kava to excess. She attributes his dry, scaly skin to excessive kava use.

Upon questioning, Mr. J says he consumes about a half-pound of kava root per day. He says he uses the root to make a tea-like beverage that, like alcohol, induces euphoria and relaxation. He says he began doing this in his youth back in Fiji, and now drinks “many cups” of kava per day.

Mr. J states that his current episode of strange movements and visual hallucinations began hours after he drank several cups of kava the day before police brought him to the ER. He considers his new psychiatric symptoms Jesus’ punishment for drinking kava.

The authors’ observations

Mr. J’s persecutory delusions suggest that he does not fully associate his symptoms with excessive kava use, but his abnormal movements, weight loss, skin changes, liver function abnormalities, and mental status changes are known adverse effects of kava.³ We diagnose substance-induced delirium rather than substance intoxication or substance-induced psychosis because:

• Mr. J’s cognitive symptoms are more severe than those caused by kava intoxication
  
• his psychotic symptoms occur only when he is delirious
  
• his disturbed consciousness, cognitive, and perceptual disturbances and the temporal relationship between symptom onset and massive kava use match DSM-IV-TR criteria for substance-induced delirium.⁴
  

Being aware of cultural customs and beliefs in your practice area can alert you to herbal substance use in various populations, such as kava by patients from the South Pacific or echinacea, goldenseal, and burdock by some Native Americans (see Related resources).

Medicinal use. Patients often use kava and other herbal supplements—including fatty acids, ginkgo biloba, ginseng, St. John’s wort, valerian, and others—with or instead of prescription drugs to alleviate psychiatric symptoms. Complementary and alternative medicine practitioners use kava to treat anxiety, for example (Box).

Anxiety and depression are among the most common reasons persons seek complementary or alternative treatment. In a national survey, 57% of respondents who suffered “anxiety attacks” and 54% of those with “severe depression” reported using such therapies.⁸ Nearly 1 in 5 persons who take prescription drugs also take herbs and/or high-dose vitamin supplements.⁹

Herbal products have been shown to cause adverse effects (Table 1).¹⁰ Kava, for example, has been associated with hepatotoxicity, dermopathy, movement disorders, GI disturbance, and weight loss. Standardized extracts such as capsules and tinctures appear more likely to cause adverse effects than traditional extractions, such as a beverage made by infusing kava root.⁵

Kava toxicity has been reported among heavy users. Although the dosage at which kava becomes dangerous is unknown, the FDA recommends that users not exceed typical dosages (50 to 280 mg/d) and use kava only under a physician’s supervision.¹¹

Also, interactions between herbal products and allopathic medications can cause substantial morbidity (Table 2). St. John’s wort, for example, can lead to serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs)¹² and can reduce blood levels of psychotropics metabolized by the cytochrome P-450 3A4 isoenzyme, such as alprazolam and carbamazepine.

Mr. J combined kava with clonazepam. Both substances affect gamma-aminobutyric (GABA) receptors, increasing the risk of sedation by depressing the CNS.

Table 1

Possible adverse effects of herbal supplements
used for psychiatric symptoms

Potential adverse interactions between psychotropics and complementary/alternative medications

Ask about alternative medicine use

According to a national survey,¹³ many patients do not tell allopathic physicians they are using complementary or alternative medications because:

• “It wasn’t important for the doctor to know.”
  
• “The doctor never asked.”
  
• “It was none of the doctor’s business.”
  
• “The doctor would not understand.”
  
• or “The doctor would disapprove or discourage CAM use.”
  

• routinely question patients about use of alternative therapies
  
• discuss safety and efficacy of commonly used alternative treatments
  
• discuss merits of alternative treatments
  
• provide information on the effectiveness and risks of various treatments
  
• learn about alternative therapies by consulting the Physicians’ Desk Reference (PDR) for Herbal Medicines or similar references
  
• help patients make decisions about alternative treatments, such as finding a qualified, licensed alternative provider.
  

Treatment: quick resolution

We admit Mr. J to the inpatient psychiatry unit. There, we continue his outpatient prescription medications at the same dosages and block access to nonprescription substances. His symptoms begin to improve during the first day of hospitalization. His choreoathetosis, hallucinations, and confusion resolve within 48 hours, and he is medically stable.

We discharge Mr. J after 2 days and continue citalopram and clonazepam at the same dosages.

The authors’ observations

Kava reaches peak plasma levels 1.8 hours after oral dosing and has a short (9-hour) elimination half-life. As a result, kava intoxication symptoms tend to resolve rapidly, as in Mr. J’s case.

Although Mr. J is medically stable, liver damage associated with kava use can be irreversible, prompting some European countries to ban its sale. Make sure patients who report kava use are aware of its hepatotoxicity risk.

Follow-up: kicking the kava habit

Two weeks after Mr. J’s discharge, his psychiatrist notes that his mental status has returned to baseline and that his skin has improved dramatically. The patient is following his citalopram and clonazepam regimen, and he seems more aware of kava’s potential adverse effects.

Mr. J reports that he has not consumed kava since his hospitalization. He has been eating four meals per day and has gained 9 lb. He is pleased with his improved appetite and is motivated to continue abstaining from kava.

Related resources

• National Center for Complementary and Alternative Medicine. http://nccam.nih.gov.
  
• Physicians Desk Reference (PDR) for herbal medicines, 3rd ed. Montvale, NJ: Thomson PDR; 2004.
  
• Ernst E, Pittler MH, Stevinson C, et al. The desktop guide to complementary and alternative medicine. Edinburgh, UK: Mosby; 2001.
  

• Alprazolam • Xanax
  
• Buspirone • BuSpar
  
• Carbamazepine • Equetro, others
  
• Carbidopa • Lodosyn
  
• Citalopram • Celexa
  
• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Trazodone • Desyrel
  

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

History: a lovelorn life

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

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

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

poll here

The authors’ observations

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

Ask the patient:

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

Table 1

Mental status examination signs that suggest a PDD

Treatment: medication and exploration

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

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

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

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

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

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

poll hereTable 2

Autism or Asperger’s? Watch for these distinguishing features

The authors’ observations

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

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

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

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

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

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

Related resources

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

• Escitalopram • Lexapro
  

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

History: a lovelorn life

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

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

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

poll here

The authors’ observations

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

Ask the patient:

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

Table 1

Mental status examination signs that suggest a PDD

Treatment: medication and exploration

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

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

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

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

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

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

poll hereTable 2

Autism or Asperger’s? Watch for these distinguishing features

The authors’ observations

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

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

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

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

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

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

Related resources

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

• Escitalopram • Lexapro
  

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

History: a lovelorn life

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

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

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

poll here

The authors’ observations

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

Ask the patient:

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

Table 1

Mental status examination signs that suggest a PDD

Treatment: medication and exploration

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

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

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

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

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

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

poll hereTable 2

Autism or Asperger’s? Watch for these distinguishing features

The authors’ observations

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

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

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

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

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

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

Related resources

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

• Escitalopram • Lexapro
  

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

History: ‘leaving town’

Mr. S, age 58, escaped repeatedly from his group home over 4 weeks. During one episode, he removed mail from neighbors’ mailboxes and tried to direct midday traffic. He would disappear for a few hours, sometimes overnight, before returning or being brought back by police.

The patient—who has had schizophrenia with catatonic features for 30 years—offered assorted explanations for escaping, most of them based on delusional beliefs, such as “I’m leaving town to get married” or “I’m late for engineering class.”

Since his last escape 3 weeks ago, Mr. S has remained in the group home without incident but has not been reporting for his usual outpatient psychiatric care. One day, he finally presents to us at the group home sponsor’s urging.

On evaluation, Mr. S shows stereotyped speech, staring, posturing, speech-prompt mutism, and odd mannerisms such as saluting. He has not been bathing or sleeping and smiles inappropriately. He speaks only when spoken to and answers with short phrases punctuated with ”By the grace of the good Lord.”

The authors’ observations

DSM-IV-TR requires at least two features to diagnose catatonic schizophrenia:

• peculiar voluntary movements
  
• extreme negativism
  
• excessive motor activity
  
• echolalia or echopraxia
  
• motoric immobility.¹
  

Catatonia is common among the chronic mentally ill,² yet it often goes undiagnosed.³ As a form of psychosis, catatonia might lead to greater functional impairment if not treated.

Treatment: time to try clozapine?

Over 10 years, numerous antipsychotic regimens plus adjunctive valproic acid, 500 mg tid, or lorazepam, up to 2 mg tid, have not lessened Mr. S’ psychosis and impulsivity. We start clozapine, 400 mg/d, and order twice-monthly blood tests to check for clozapine-induced agranulocytosis.

After nearly 6 months, some catatonic features improve gradually based on clinical interview. Serum clozapine is 363 ng/mL.

poll here

The authors’ observations

Second-generation antipsychotics (SGAs) are favored over first-generation antipsychotics to treat schizophrenia with catatonic features (Table),^4,5 but no drug in either class has worked for Mr. S.

ECT can alleviate catatonic schizophrenia,^4,6 but this option often is not available because the clinician fears a negative outcome would prompt legal action, or the guardian or next of kin do not consent to the procedure.³ We considered referring Mr. S to an ECT provider, but he has no legal guardian to provide consent. The group home sponsor also objected to ECT because Mr. S would have been sent out of town for treatment.

Catatonia patients who are immobile, physically compromised, and refuse food and drink typically are considered ECT candidates. Mr. S eats and drinks regularly and is physically able.

Lorazepam can produce rapid response, but it can be addictive.² Also, an adjunctive 2 mg/d dosage showed no effect.

Clozapine monotherapy has shown effectiveness in catatonic schizophrenia⁷ and might be an option after other antipsychotics have failed.

Table 1

Treatments for catatonia: risks and benefits

Complication: agranulocytosis, then nms

Six months after starting clozapine, Mr. S starts having diaphoresis and night sweats, suggesting neutropenia. Blood testing shows a white blood cell count (WBC) of 3.6/μL, down from 4.6/μL 2 weeks before (normal range, 4.6 to 11/μL).

One week later, Mr. S’ WBC is 1.6/μL with a 46% relative neutrophil value (normal range, 50% to 70%) and an absolute neutrophil count of 736 (normal range, 2,500 to 7,000).

We diagnose agranulocytosis and stop clozapine, but Mr. S’ WBC continues to fall over 2 weeks to 0.8/μL with a 16% relative and 128 absolute neutrophil count. After 1 more week, his WBC increases to 2.6/μL and returns to normal 1 week later—4 weeks after stopping clozapine

We then target Mr. S’ catatonia with intramuscular haloperidol, 100 mg/d for 4 weeks, and ziprasidone, 80 mg bid with food. He tolerates this combination but gradually develops tremor and rigidity. Six weeks later, we add levodopa/carbidopa, 25/250 mg bid for his movement problems.

Two weeks later, Mr. S is sweating profusely, disoriented, rigid, and febrile (104.6°F). We diagnose neuroleptic malignant syndrome (NMS), stop both antipsychotics, and admit him for treatment. We start lorazepam, 1 mg tid for catatonia; bromocriptine, 250 mg bid for rigidity; and continue levodopa/carbidopa at the same dosage. We also add dantrolene, 25 mg tid for 5 days for fever and rigidity, and provide a cooling blanket for hyperthermia.

Mr. S’ fever, autonomic changes, and diaphoresis diminish within 3 days. Rigidity and mental status improve gradually over 2 weeks. We discharge him after 10 days.

poll here

The author’s observations

Catatonia is a recognized risk factor for NMS. White and Robins⁸ described 17 patients with a catatonic syndrome that developed into NMS within 5 to 96 hours of starting a neuroleptic. Sachdev developed an NMS rating scale that includes catatonic symptoms.⁹

Northoff,¹⁰ however, associates NMS with D2 receptor blockage in the basal ganglia and relates catatonia to a frontocortical gamma-aminobutyric acid (GABA) dysfunction. Based on this theory, haloperidol—which offers a higher D2 blockade than do SGAs such as ziprasidone—might have contributed to Mr. S’ NMS.

Some evidence suggests that lorazepam—which works on gamma-aminobutyric acid ionotropic type A (GABAA) receptors—helps treat catatonia in NMS and improves rigidity, hyperthermia, and autonomic signs.¹¹

Treatment: which agents will work?

Three weeks after his discharge, we restart ziprasidone, 40 mg bid for Mr. S’ catatonic schizophrenia. He remains free of NMS symptoms but still has mannerisms (posturing, staring, immobility, stereotypic scratching on his face).

Over 1 year, Mr. S is hospitalized repeatedly because of persistent impulsivity and delusions. He has failed numerous antipsychotic regimens lasting 1 month or longer, including olanzapine, up to 30 mg/d; quetiapine, 300 mg tid; and risperidone, 2 mg tid. Adding a first-generation antipsychotic either does not help (as with perphenazine, 12 mg/d) or diminishes his memory (as with chlorpromazine, 250 mg/d). The anticholinergic benztropine, 2 mg bid, also is ineffective.

Combination quetiapine, 300 mg/d, and the antiviral amantadine, 100 mg tid, improve Mr. S’ stereotypy at first, but his delusions intensify within 1 week. His Bush-Francis Catatonia Rating Scale scores range from 9 (indicating moderate catatonia) to 16 (persistent catatonic features).¹²

poll here

The authors’ observations

Catatonic schizophrenia’s pathophysiology and response to medication might differ compared with other schizophrenia forms.¹³ Dopamine D2 hypoactivity, glutamate N-methyl-D-aspartate (NMDA) hyperactivity, or GABAA hypoactivity are believed to cause catatonia.^3,6,7 GABA agonists, anticonvulsants, dopamine agonists, SGAs, and NMDA antagonists target these pathophysiologies, but patients with a catatonia subtype often respond to only one type of medication.

Lorazepam exerts an anticatatonic effect by binding to GABAA receptors and increasing GABA activity. Lorazepam can help some patients with schizophrenia but has not shown benefit when added to an antipsychotic for chronic catatonia.^6,14

SGAs can provide marked improvement in patients with catatonic schizophrenia.⁵

Salokangas et al¹⁵ note that “atypicals” pass more dopamine to the D2 receptor when dopamine is low in the basal ganglia. This suggests that SGAs with low D2 binding—such as clozapine, olanzapine, and quetiapine—are more beneficial than other SGAs for catatonia. Serotonin binding or other mechanisms might add to these drugs’ anticatatonic effect.⁷

Anticonvulsants. Adjunctive anticonvulsant therapy might alleviate catatonia by increasing GABA activity or by causing a modest antiglutaminergic effect, as reported with carbamazepine or valproic acid.¹⁶ Anticholinergics also might help treat neuroleptic-induced catatonia.¹⁷

Amantadine—FDA-approved to treat Parkinson’s disease and extrapyramidal disease—can alleviate catatonia by blocking hyperglutamatergic excitotoxicity in neurons, thus blocking NMDA receptors.¹⁸ As with Mr. S, however, amantadine can worsen psychosis by increasing dopamine release.

Memantine—an NMDA receptor antagonist indicated for moderate to severe Alzheimer’s disease—also blocks hyperglutamatergic excitotoxicity in neurons. The medication has shown effectiveness for treating catatonic schizophrenia in case reports,^19-21 but 3 patients have reported memantine-induced psychosis and seizures.²¹

Some might argue that Mr. S’ delusions are predominant and more compelling than his catatonia, but these did not hamper his ability to live in a group home. His catatonia-related negativism, impulsivity, and inability to cooperate are what led to frequent hospitalization.

Follow-up: treatment change

We stop amantadine, add memantine, 10 mg bid, and titrate quetiapine over 2 weeks to 900 mg/d. Mr. S’ catatonia improves but some delusions persist. We add olanzapine, 7.5 mg bid, and within 2 weeks Mr. S is less delusional and more cooperative.

We discharge Mr. S on the above medications, plus:

• lorazepam, 1 mg each morning and 2 mg nightly, which he has been taking for catatonia for about 1 year
  
• trazodone, 150 mg bid, which we added 6 months ago to help him sleep and reduce psychomotor excitement
  
• ranitidine, 150 mg bid, for gastroesophageal reflux disorder
  
• and levothyroxine, 0.5 mg/d, for comobrid hypothyroidism. His thyroid-stimulating hormone level is normal.
  

We see Mr. S monthly. He is still impulsive at times, occasionally collecting his neighbors’ newspapers and mail despite instructions from group home staff not to do so. Yet his sponsors say Mr. S is “like a new person.” He talks spontaneously, interacts, and is cooperative. He has not been hospitalized for more than 1 year.

The authors’ observations

Mr. S responded favorably to clozapine but cannot tolerate it. With a combination of two other SGAs, a patient might gain the benefits of clozapine without the need for frequent blood draws or the risk of agranulocytosis, other side effects, or interactions between clozapine and other drugs. Adding memantine was necessary to improve the catatonic features that prevented his return to the group home.

Related resources

• World Federation of Societies of Biological Psychiatry. www.wfsbp.com.
  
• Neuroleptic Malignant Syndrome Information Service. www.nmsis.org.
  
• Mann SC, Caroff SN, Keck PE Jr, Lazarus A. Neuroleptic malignant syndrome and related conditions, 2nd ed. Arlington, VA: American Psychiatric Press; 2003:1-44.
  
• Ungvari GS (ed). Catatonia-an anthology of classical contributions. Hong Kong: Scientific Communications International; 2006.
  

• Amantadine • Symmetrel
  
• Benztropine • Cogentin
  
• Bromocriptine • Parlodel
  
• Carbamazepine • Equetro, others
  
• Chlorpromazine • Thorazine
  
• Clozapine • Clozaril
  
• Dantrolene • Dantrium
  
• Haloperidol • Haldol
  
• Levodopa/carbidopa • Sinemet
  
• Levothyroxine • Synthroid
  
• Lorazepam • Ativan
  
• Memantine • Namenda
  
• Olanzapine • Zyprexa
  
• Perphenazine • Trilafon
  
• Quetiapine • Seroquel
  
• Ranitidine • Zantac
  
• Risperidone • Risperdal
  
• Trazodone • Desyrel
  
• Valproic acid • Depakene
  
• Ziprasidone • Geodon
  

Dr. Carroll is a speaker for Abbott Laboratories, AstraZeneca Pharmaceuticals, Bristol Myers-Squibb Co., Forest Pharmaceuticals, Janssen Pharmaceutica, and Pfizer.

Dr. Thomas receives grant support from Pfizer and is a speaker for Abbott Laboratories, AstraZeneca Pharmaceuticals, and Pfizer.

Dr. Tugrul is a consultant to and speaker for Bristol Myers-Squibb Co. and Eli Lilly and Co.

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

Acknowledgment

The authors thank Francisco José Appiani, MD, chairman, psychiatry department, Military Hospital of Campo de Mayo, Buenos Aires, Argentina, and Vijay Jayanti, BS, medical student, The Ohio State University, Columbus, for their help with this article.

History: ‘leaving town’

Mr. S, age 58, escaped repeatedly from his group home over 4 weeks. During one episode, he removed mail from neighbors’ mailboxes and tried to direct midday traffic. He would disappear for a few hours, sometimes overnight, before returning or being brought back by police.

The patient—who has had schizophrenia with catatonic features for 30 years—offered assorted explanations for escaping, most of them based on delusional beliefs, such as “I’m leaving town to get married” or “I’m late for engineering class.”

Since his last escape 3 weeks ago, Mr. S has remained in the group home without incident but has not been reporting for his usual outpatient psychiatric care. One day, he finally presents to us at the group home sponsor’s urging.

On evaluation, Mr. S shows stereotyped speech, staring, posturing, speech-prompt mutism, and odd mannerisms such as saluting. He has not been bathing or sleeping and smiles inappropriately. He speaks only when spoken to and answers with short phrases punctuated with ”By the grace of the good Lord.”

The authors’ observations

DSM-IV-TR requires at least two features to diagnose catatonic schizophrenia:

• peculiar voluntary movements
  
• extreme negativism
  
• excessive motor activity
  
• echolalia or echopraxia
  
• motoric immobility.¹
  

Catatonia is common among the chronic mentally ill,² yet it often goes undiagnosed.³ As a form of psychosis, catatonia might lead to greater functional impairment if not treated.

Treatment: time to try clozapine?

Over 10 years, numerous antipsychotic regimens plus adjunctive valproic acid, 500 mg tid, or lorazepam, up to 2 mg tid, have not lessened Mr. S’ psychosis and impulsivity. We start clozapine, 400 mg/d, and order twice-monthly blood tests to check for clozapine-induced agranulocytosis.

After nearly 6 months, some catatonic features improve gradually based on clinical interview. Serum clozapine is 363 ng/mL.

poll here

The authors’ observations

Second-generation antipsychotics (SGAs) are favored over first-generation antipsychotics to treat schizophrenia with catatonic features (Table),^4,5 but no drug in either class has worked for Mr. S.

ECT can alleviate catatonic schizophrenia,^4,6 but this option often is not available because the clinician fears a negative outcome would prompt legal action, or the guardian or next of kin do not consent to the procedure.³ We considered referring Mr. S to an ECT provider, but he has no legal guardian to provide consent. The group home sponsor also objected to ECT because Mr. S would have been sent out of town for treatment.

Catatonia patients who are immobile, physically compromised, and refuse food and drink typically are considered ECT candidates. Mr. S eats and drinks regularly and is physically able.

Lorazepam can produce rapid response, but it can be addictive.² Also, an adjunctive 2 mg/d dosage showed no effect.

Clozapine monotherapy has shown effectiveness in catatonic schizophrenia⁷ and might be an option after other antipsychotics have failed.

Table 1

Treatments for catatonia: risks and benefits

Complication: agranulocytosis, then nms

Six months after starting clozapine, Mr. S starts having diaphoresis and night sweats, suggesting neutropenia. Blood testing shows a white blood cell count (WBC) of 3.6/μL, down from 4.6/μL 2 weeks before (normal range, 4.6 to 11/μL).

One week later, Mr. S’ WBC is 1.6/μL with a 46% relative neutrophil value (normal range, 50% to 70%) and an absolute neutrophil count of 736 (normal range, 2,500 to 7,000).

We diagnose agranulocytosis and stop clozapine, but Mr. S’ WBC continues to fall over 2 weeks to 0.8/μL with a 16% relative and 128 absolute neutrophil count. After 1 more week, his WBC increases to 2.6/μL and returns to normal 1 week later—4 weeks after stopping clozapine

We then target Mr. S’ catatonia with intramuscular haloperidol, 100 mg/d for 4 weeks, and ziprasidone, 80 mg bid with food. He tolerates this combination but gradually develops tremor and rigidity. Six weeks later, we add levodopa/carbidopa, 25/250 mg bid for his movement problems.

Two weeks later, Mr. S is sweating profusely, disoriented, rigid, and febrile (104.6°F). We diagnose neuroleptic malignant syndrome (NMS), stop both antipsychotics, and admit him for treatment. We start lorazepam, 1 mg tid for catatonia; bromocriptine, 250 mg bid for rigidity; and continue levodopa/carbidopa at the same dosage. We also add dantrolene, 25 mg tid for 5 days for fever and rigidity, and provide a cooling blanket for hyperthermia.

Mr. S’ fever, autonomic changes, and diaphoresis diminish within 3 days. Rigidity and mental status improve gradually over 2 weeks. We discharge him after 10 days.

poll here

The author’s observations

Catatonia is a recognized risk factor for NMS. White and Robins⁸ described 17 patients with a catatonic syndrome that developed into NMS within 5 to 96 hours of starting a neuroleptic. Sachdev developed an NMS rating scale that includes catatonic symptoms.⁹

Northoff,¹⁰ however, associates NMS with D2 receptor blockage in the basal ganglia and relates catatonia to a frontocortical gamma-aminobutyric acid (GABA) dysfunction. Based on this theory, haloperidol—which offers a higher D2 blockade than do SGAs such as ziprasidone—might have contributed to Mr. S’ NMS.

Some evidence suggests that lorazepam—which works on gamma-aminobutyric acid ionotropic type A (GABAA) receptors—helps treat catatonia in NMS and improves rigidity, hyperthermia, and autonomic signs.¹¹

Treatment: which agents will work?

Three weeks after his discharge, we restart ziprasidone, 40 mg bid for Mr. S’ catatonic schizophrenia. He remains free of NMS symptoms but still has mannerisms (posturing, staring, immobility, stereotypic scratching on his face).

Over 1 year, Mr. S is hospitalized repeatedly because of persistent impulsivity and delusions. He has failed numerous antipsychotic regimens lasting 1 month or longer, including olanzapine, up to 30 mg/d; quetiapine, 300 mg tid; and risperidone, 2 mg tid. Adding a first-generation antipsychotic either does not help (as with perphenazine, 12 mg/d) or diminishes his memory (as with chlorpromazine, 250 mg/d). The anticholinergic benztropine, 2 mg bid, also is ineffective.

Combination quetiapine, 300 mg/d, and the antiviral amantadine, 100 mg tid, improve Mr. S’ stereotypy at first, but his delusions intensify within 1 week. His Bush-Francis Catatonia Rating Scale scores range from 9 (indicating moderate catatonia) to 16 (persistent catatonic features).¹²

poll here

The authors’ observations

Catatonic schizophrenia’s pathophysiology and response to medication might differ compared with other schizophrenia forms.¹³ Dopamine D2 hypoactivity, glutamate N-methyl-D-aspartate (NMDA) hyperactivity, or GABAA hypoactivity are believed to cause catatonia.^3,6,7 GABA agonists, anticonvulsants, dopamine agonists, SGAs, and NMDA antagonists target these pathophysiologies, but patients with a catatonia subtype often respond to only one type of medication.

Lorazepam exerts an anticatatonic effect by binding to GABAA receptors and increasing GABA activity. Lorazepam can help some patients with schizophrenia but has not shown benefit when added to an antipsychotic for chronic catatonia.^6,14

SGAs can provide marked improvement in patients with catatonic schizophrenia.⁵

Salokangas et al¹⁵ note that “atypicals” pass more dopamine to the D2 receptor when dopamine is low in the basal ganglia. This suggests that SGAs with low D2 binding—such as clozapine, olanzapine, and quetiapine—are more beneficial than other SGAs for catatonia. Serotonin binding or other mechanisms might add to these drugs’ anticatatonic effect.⁷

Anticonvulsants. Adjunctive anticonvulsant therapy might alleviate catatonia by increasing GABA activity or by causing a modest antiglutaminergic effect, as reported with carbamazepine or valproic acid.¹⁶ Anticholinergics also might help treat neuroleptic-induced catatonia.¹⁷

Amantadine—FDA-approved to treat Parkinson’s disease and extrapyramidal disease—can alleviate catatonia by blocking hyperglutamatergic excitotoxicity in neurons, thus blocking NMDA receptors.¹⁸ As with Mr. S, however, amantadine can worsen psychosis by increasing dopamine release.

Memantine—an NMDA receptor antagonist indicated for moderate to severe Alzheimer’s disease—also blocks hyperglutamatergic excitotoxicity in neurons. The medication has shown effectiveness for treating catatonic schizophrenia in case reports,^19-21 but 3 patients have reported memantine-induced psychosis and seizures.²¹

Some might argue that Mr. S’ delusions are predominant and more compelling than his catatonia, but these did not hamper his ability to live in a group home. His catatonia-related negativism, impulsivity, and inability to cooperate are what led to frequent hospitalization.

Follow-up: treatment change

We stop amantadine, add memantine, 10 mg bid, and titrate quetiapine over 2 weeks to 900 mg/d. Mr. S’ catatonia improves but some delusions persist. We add olanzapine, 7.5 mg bid, and within 2 weeks Mr. S is less delusional and more cooperative.

We discharge Mr. S on the above medications, plus:

• lorazepam, 1 mg each morning and 2 mg nightly, which he has been taking for catatonia for about 1 year
  
• trazodone, 150 mg bid, which we added 6 months ago to help him sleep and reduce psychomotor excitement
  
• ranitidine, 150 mg bid, for gastroesophageal reflux disorder
  
• and levothyroxine, 0.5 mg/d, for comobrid hypothyroidism. His thyroid-stimulating hormone level is normal.
  

We see Mr. S monthly. He is still impulsive at times, occasionally collecting his neighbors’ newspapers and mail despite instructions from group home staff not to do so. Yet his sponsors say Mr. S is “like a new person.” He talks spontaneously, interacts, and is cooperative. He has not been hospitalized for more than 1 year.

The authors’ observations

Mr. S responded favorably to clozapine but cannot tolerate it. With a combination of two other SGAs, a patient might gain the benefits of clozapine without the need for frequent blood draws or the risk of agranulocytosis, other side effects, or interactions between clozapine and other drugs. Adding memantine was necessary to improve the catatonic features that prevented his return to the group home.

Related resources

• World Federation of Societies of Biological Psychiatry. www.wfsbp.com.
  
• Neuroleptic Malignant Syndrome Information Service. www.nmsis.org.
  
• Mann SC, Caroff SN, Keck PE Jr, Lazarus A. Neuroleptic malignant syndrome and related conditions, 2nd ed. Arlington, VA: American Psychiatric Press; 2003:1-44.
  
• Ungvari GS (ed). Catatonia-an anthology of classical contributions. Hong Kong: Scientific Communications International; 2006.
  

• Amantadine • Symmetrel
  
• Benztropine • Cogentin
  
• Bromocriptine • Parlodel
  
• Carbamazepine • Equetro, others
  
• Chlorpromazine • Thorazine
  
• Clozapine • Clozaril
  
• Dantrolene • Dantrium
  
• Haloperidol • Haldol
  
• Levodopa/carbidopa • Sinemet
  
• Levothyroxine • Synthroid
  
• Lorazepam • Ativan
  
• Memantine • Namenda
  
• Olanzapine • Zyprexa
  
• Perphenazine • Trilafon
  
• Quetiapine • Seroquel
  
• Ranitidine • Zantac
  
• Risperidone • Risperdal
  
• Trazodone • Desyrel
  
• Valproic acid • Depakene
  
• Ziprasidone • Geodon
  

Dr. Carroll is a speaker for Abbott Laboratories, AstraZeneca Pharmaceuticals, Bristol Myers-Squibb Co., Forest Pharmaceuticals, Janssen Pharmaceutica, and Pfizer.

Dr. Thomas receives grant support from Pfizer and is a speaker for Abbott Laboratories, AstraZeneca Pharmaceuticals, and Pfizer.

Dr. Tugrul is a consultant to and speaker for Bristol Myers-Squibb Co. and Eli Lilly and Co.

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

Acknowledgment

The authors thank Francisco José Appiani, MD, chairman, psychiatry department, Military Hospital of Campo de Mayo, Buenos Aires, Argentina, and Vijay Jayanti, BS, medical student, The Ohio State University, Columbus, for their help with this article.

History: ‘leaving town’

Mr. S, age 58, escaped repeatedly from his group home over 4 weeks. During one episode, he removed mail from neighbors’ mailboxes and tried to direct midday traffic. He would disappear for a few hours, sometimes overnight, before returning or being brought back by police.

The patient—who has had schizophrenia with catatonic features for 30 years—offered assorted explanations for escaping, most of them based on delusional beliefs, such as “I’m leaving town to get married” or “I’m late for engineering class.”

Since his last escape 3 weeks ago, Mr. S has remained in the group home without incident but has not been reporting for his usual outpatient psychiatric care. One day, he finally presents to us at the group home sponsor’s urging.

On evaluation, Mr. S shows stereotyped speech, staring, posturing, speech-prompt mutism, and odd mannerisms such as saluting. He has not been bathing or sleeping and smiles inappropriately. He speaks only when spoken to and answers with short phrases punctuated with ”By the grace of the good Lord.”

The authors’ observations

DSM-IV-TR requires at least two features to diagnose catatonic schizophrenia:

• peculiar voluntary movements
  
• extreme negativism
  
• excessive motor activity
  
• echolalia or echopraxia
  
• motoric immobility.¹
  

Catatonia is common among the chronic mentally ill,² yet it often goes undiagnosed.³ As a form of psychosis, catatonia might lead to greater functional impairment if not treated.

Treatment: time to try clozapine?

Over 10 years, numerous antipsychotic regimens plus adjunctive valproic acid, 500 mg tid, or lorazepam, up to 2 mg tid, have not lessened Mr. S’ psychosis and impulsivity. We start clozapine, 400 mg/d, and order twice-monthly blood tests to check for clozapine-induced agranulocytosis.

After nearly 6 months, some catatonic features improve gradually based on clinical interview. Serum clozapine is 363 ng/mL.

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The authors’ observations

Second-generation antipsychotics (SGAs) are favored over first-generation antipsychotics to treat schizophrenia with catatonic features (Table),^4,5 but no drug in either class has worked for Mr. S.

ECT can alleviate catatonic schizophrenia,^4,6 but this option often is not available because the clinician fears a negative outcome would prompt legal action, or the guardian or next of kin do not consent to the procedure.³ We considered referring Mr. S to an ECT provider, but he has no legal guardian to provide consent. The group home sponsor also objected to ECT because Mr. S would have been sent out of town for treatment.

Catatonia patients who are immobile, physically compromised, and refuse food and drink typically are considered ECT candidates. Mr. S eats and drinks regularly and is physically able.

Lorazepam can produce rapid response, but it can be addictive.² Also, an adjunctive 2 mg/d dosage showed no effect.

Clozapine monotherapy has shown effectiveness in catatonic schizophrenia⁷ and might be an option after other antipsychotics have failed.

Table 1

Treatments for catatonia: risks and benefits

Complication: agranulocytosis, then nms

Six months after starting clozapine, Mr. S starts having diaphoresis and night sweats, suggesting neutropenia. Blood testing shows a white blood cell count (WBC) of 3.6/μL, down from 4.6/μL 2 weeks before (normal range, 4.6 to 11/μL).

One week later, Mr. S’ WBC is 1.6/μL with a 46% relative neutrophil value (normal range, 50% to 70%) and an absolute neutrophil count of 736 (normal range, 2,500 to 7,000).

We diagnose agranulocytosis and stop clozapine, but Mr. S’ WBC continues to fall over 2 weeks to 0.8/μL with a 16% relative and 128 absolute neutrophil count. After 1 more week, his WBC increases to 2.6/μL and returns to normal 1 week later—4 weeks after stopping clozapine

We then target Mr. S’ catatonia with intramuscular haloperidol, 100 mg/d for 4 weeks, and ziprasidone, 80 mg bid with food. He tolerates this combination but gradually develops tremor and rigidity. Six weeks later, we add levodopa/carbidopa, 25/250 mg bid for his movement problems.

Two weeks later, Mr. S is sweating profusely, disoriented, rigid, and febrile (104.6°F). We diagnose neuroleptic malignant syndrome (NMS), stop both antipsychotics, and admit him for treatment. We start lorazepam, 1 mg tid for catatonia; bromocriptine, 250 mg bid for rigidity; and continue levodopa/carbidopa at the same dosage. We also add dantrolene, 25 mg tid for 5 days for fever and rigidity, and provide a cooling blanket for hyperthermia.

Mr. S’ fever, autonomic changes, and diaphoresis diminish within 3 days. Rigidity and mental status improve gradually over 2 weeks. We discharge him after 10 days.

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The author’s observations

Catatonia is a recognized risk factor for NMS. White and Robins⁸ described 17 patients with a catatonic syndrome that developed into NMS within 5 to 96 hours of starting a neuroleptic. Sachdev developed an NMS rating scale that includes catatonic symptoms.⁹

Northoff,¹⁰ however, associates NMS with D2 receptor blockage in the basal ganglia and relates catatonia to a frontocortical gamma-aminobutyric acid (GABA) dysfunction. Based on this theory, haloperidol—which offers a higher D2 blockade than do SGAs such as ziprasidone—might have contributed to Mr. S’ NMS.

Some evidence suggests that lorazepam—which works on gamma-aminobutyric acid ionotropic type A (GABAA) receptors—helps treat catatonia in NMS and improves rigidity, hyperthermia, and autonomic signs.¹¹

Treatment: which agents will work?

Three weeks after his discharge, we restart ziprasidone, 40 mg bid for Mr. S’ catatonic schizophrenia. He remains free of NMS symptoms but still has mannerisms (posturing, staring, immobility, stereotypic scratching on his face).

Over 1 year, Mr. S is hospitalized repeatedly because of persistent impulsivity and delusions. He has failed numerous antipsychotic regimens lasting 1 month or longer, including olanzapine, up to 30 mg/d; quetiapine, 300 mg tid; and risperidone, 2 mg tid. Adding a first-generation antipsychotic either does not help (as with perphenazine, 12 mg/d) or diminishes his memory (as with chlorpromazine, 250 mg/d). The anticholinergic benztropine, 2 mg bid, also is ineffective.

Combination quetiapine, 300 mg/d, and the antiviral amantadine, 100 mg tid, improve Mr. S’ stereotypy at first, but his delusions intensify within 1 week. His Bush-Francis Catatonia Rating Scale scores range from 9 (indicating moderate catatonia) to 16 (persistent catatonic features).¹²

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The authors’ observations

Catatonic schizophrenia’s pathophysiology and response to medication might differ compared with other schizophrenia forms.¹³ Dopamine D2 hypoactivity, glutamate N-methyl-D-aspartate (NMDA) hyperactivity, or GABAA hypoactivity are believed to cause catatonia.^3,6,7 GABA agonists, anticonvulsants, dopamine agonists, SGAs, and NMDA antagonists target these pathophysiologies, but patients with a catatonia subtype often respond to only one type of medication.

Lorazepam exerts an anticatatonic effect by binding to GABAA receptors and increasing GABA activity. Lorazepam can help some patients with schizophrenia but has not shown benefit when added to an antipsychotic for chronic catatonia.^6,14

SGAs can provide marked improvement in patients with catatonic schizophrenia.⁵

Salokangas et al¹⁵ note that “atypicals” pass more dopamine to the D2 receptor when dopamine is low in the basal ganglia. This suggests that SGAs with low D2 binding—such as clozapine, olanzapine, and quetiapine—are more beneficial than other SGAs for catatonia. Serotonin binding or other mechanisms might add to these drugs’ anticatatonic effect.⁷

Anticonvulsants. Adjunctive anticonvulsant therapy might alleviate catatonia by increasing GABA activity or by causing a modest antiglutaminergic effect, as reported with carbamazepine or valproic acid.¹⁶ Anticholinergics also might help treat neuroleptic-induced catatonia.¹⁷

Amantadine—FDA-approved to treat Parkinson’s disease and extrapyramidal disease—can alleviate catatonia by blocking hyperglutamatergic excitotoxicity in neurons, thus blocking NMDA receptors.¹⁸ As with Mr. S, however, amantadine can worsen psychosis by increasing dopamine release.

Memantine—an NMDA receptor antagonist indicated for moderate to severe Alzheimer’s disease—also blocks hyperglutamatergic excitotoxicity in neurons. The medication has shown effectiveness for treating catatonic schizophrenia in case reports,^19-21 but 3 patients have reported memantine-induced psychosis and seizures.²¹

Some might argue that Mr. S’ delusions are predominant and more compelling than his catatonia, but these did not hamper his ability to live in a group home. His catatonia-related negativism, impulsivity, and inability to cooperate are what led to frequent hospitalization.

Follow-up: treatment change

We stop amantadine, add memantine, 10 mg bid, and titrate quetiapine over 2 weeks to 900 mg/d. Mr. S’ catatonia improves but some delusions persist. We add olanzapine, 7.5 mg bid, and within 2 weeks Mr. S is less delusional and more cooperative.

We discharge Mr. S on the above medications, plus:

• lorazepam, 1 mg each morning and 2 mg nightly, which he has been taking for catatonia for about 1 year
  
• trazodone, 150 mg bid, which we added 6 months ago to help him sleep and reduce psychomotor excitement
  
• ranitidine, 150 mg bid, for gastroesophageal reflux disorder
  
• and levothyroxine, 0.5 mg/d, for comobrid hypothyroidism. His thyroid-stimulating hormone level is normal.
  

We see Mr. S monthly. He is still impulsive at times, occasionally collecting his neighbors’ newspapers and mail despite instructions from group home staff not to do so. Yet his sponsors say Mr. S is “like a new person.” He talks spontaneously, interacts, and is cooperative. He has not been hospitalized for more than 1 year.

The authors’ observations

Mr. S responded favorably to clozapine but cannot tolerate it. With a combination of two other SGAs, a patient might gain the benefits of clozapine without the need for frequent blood draws or the risk of agranulocytosis, other side effects, or interactions between clozapine and other drugs. Adding memantine was necessary to improve the catatonic features that prevented his return to the group home.

Related resources

• World Federation of Societies of Biological Psychiatry. www.wfsbp.com.
  
• Neuroleptic Malignant Syndrome Information Service. www.nmsis.org.
  
• Mann SC, Caroff SN, Keck PE Jr, Lazarus A. Neuroleptic malignant syndrome and related conditions, 2nd ed. Arlington, VA: American Psychiatric Press; 2003:1-44.
  
• Ungvari GS (ed). Catatonia-an anthology of classical contributions. Hong Kong: Scientific Communications International; 2006.
  

• Amantadine • Symmetrel
  
• Benztropine • Cogentin
  
• Bromocriptine • Parlodel
  
• Carbamazepine • Equetro, others
  
• Chlorpromazine • Thorazine
  
• Clozapine • Clozaril
  
• Dantrolene • Dantrium
  
• Haloperidol • Haldol
  
• Levodopa/carbidopa • Sinemet
  
• Levothyroxine • Synthroid
  
• Lorazepam • Ativan
  
• Memantine • Namenda
  
• Olanzapine • Zyprexa
  
• Perphenazine • Trilafon
  
• Quetiapine • Seroquel
  
• Ranitidine • Zantac
  
• Risperidone • Risperdal
  
• Trazodone • Desyrel
  
• Valproic acid • Depakene
  
• Ziprasidone • Geodon
  

Dr. Carroll is a speaker for Abbott Laboratories, AstraZeneca Pharmaceuticals, Bristol Myers-Squibb Co., Forest Pharmaceuticals, Janssen Pharmaceutica, and Pfizer.

Dr. Thomas receives grant support from Pfizer and is a speaker for Abbott Laboratories, AstraZeneca Pharmaceuticals, and Pfizer.

Dr. Tugrul is a consultant to and speaker for Bristol Myers-Squibb Co. and Eli Lilly and Co.

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

Acknowledgment

The authors thank Francisco José Appiani, MD, chairman, psychiatry department, Military Hospital of Campo de Mayo, Buenos Aires, Argentina, and Vijay Jayanti, BS, medical student, The Ohio State University, Columbus, for their help with this article.

History: ‘A zillion racing thoughts’

Ms. R, age 44, is referred by her primary care physician. She complains of tenseness, irritability, avolition, and fatigue. She worries incessantly that her children will get sick, a catastrophe will befall her husband, or she’ll do something wrong. She says she sometimes feels as if she’s thinking “a zillion racing thoughts.”

Once fun-loving, outgoing, and energetic, Ms. R says she began feeling unusually anxious 3 years ago. A psychiatrist diagnosed bipolar disorder type II based on her racing thoughts, irritability, low energy, and history of mood swings. Over 2 years, the psychiatrist tried combining valproic acid with bupropion, citalopram, or extended-release venlafaxine, then tried lithium monotherapy. Nothing worked.

Frustrated, Ms. R left the psychiatrist and consulted her primary care physician, who prescribed gabapentin, 200 mg each morning and 300 mg at night; fluoxetine, 50 mg/d; and quetiapine, 12.5 mg/d. Ms. R noticed no improvement and stopped the medications after 6 weeks. The physician urged her to see another psychiatrist, and she presented to us 2 weeks after stopping the medications.

Ms. R also has been feeling depressed and irritable the past 4 months and has trouble falling and staying asleep at night. She sleeps 4 to 5 hours nightly, constantly feels tired, cannot concentrate, and overeats to try to alleviate her stress. She has gained 6 pounds over 2 to 3 months and weighs 160 lb; her body mass index of 26 indicates she is overweight.

She says her worries overwhelm her and cause heart palpitations and muscle tension in her neck and shoulders. She admits to feeling “worthless,” but denies suicidal thoughts.

Ms. R describes her husband and two teenage daughters as “very supportive,” but admits that her fatigue and irritability have strained these relationships; she says she snaps at them for minor things, such as coming to dinner 1 minute late. She misses her job, which she recently quit because of her decreasing ability to function.

At intake, Ms. R says she will not resume previous medications but will consider alternatives. She refuses psychotherapy because of time constraints and transportation problems but is willing to return every 2 weeks for medication checks. She says she adhered to every prescription over 3 years with no major side effects. She has never taken an antidepressant or anxiolytic without a mood stabilizer.

Ms. R reports no medical problems, past substance use, current or past psychotic symptoms, or psychiatric hospitalizations. Her family history shows depression in one first-degree relative and anxiety in others. Her Hamilton Anxiety Scale (HAM-A) score of 20 indicates moderate anxiety. Laboratory tests ordered by her primary care physician are normal.

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The authors’ observations

Racing thoughts, irritable mood, decreased sleep, and concentration problems can point to GAD, mania associated with bipolar disorder type I, or hypomania suggesting bipolar disorder type I or II (Table 1).¹

We suspect GAD because:

• Ms. R’s thoughts “race” only when she worries
• her irritability and concentration problems seem more sustained than episodic
• she has difficulty falling and staying asleep, but her need for sleep has not decreased
• she complains of constant fatigue, whereas abnormally high energy characterizes bipolar disorder’s manic or hypomanic phase.

Does Ms. R have depression? Determining if the patient’s depressive symptoms are secondary to GAD or warrant a separate diagnosis can be difficult (Table 1). With Ms. R’s permission, we talked to her family, because collateral information often helps clarify the diagnosis. Her husband and daughters offered no significant new insights, however.

Table 1

Overlap among symptoms that suggest GAD, mania, or major depression

Treatment: Targeting the anxiety

To address Ms. R’s anxiety symptoms, we start buspirone, 5 mg tid, and titrate to 15 mg bid over 2 weeks. We choose buspirone—which is FDA-approved to treat GAD—because it is unlikely to cause a mood switch if bipolar disorder is causing Ms. R’s depression. We discuss with her the drug’s indications, benefits, and potential side effects (such as vertigo, headache, lightheadedness, and nausea).

At the first 2-week follow-up, Ms. R reports no side effects but little improvement. After another 2 weeks, she says she feels less anxiety, irritability, pain, and fewer racing thoughts. She reports less difficulty falling asleep, though she’s still sleeping only about 6 hours nightly. Her HAM-A score falls to 12, indicating mild anxiety.

Ms. R, however, says she still feels depressed, tired, distracted, unmotivated, and worthless. Her Hamilton Rating Scale for Depression (HAM-D) score of 16 indicates moderate depression.

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The authors’ observations

The persistence of Ms. R’s depressive symptoms suggests comorbid major depressive disorder (MDD). In fact, MDD and GAD are considered the most common mood-anxiety comorbidities.²

Determining whether Ms. R has unipolar depression or bipolar disorder is extremely important, considering the treatment implications. In patients with bipolar disorder, any antidepressant can trigger mania or hypomania if used without a mood stabilizer. Some studies also have associated rare cases of suicidal behavior with antidepressant use.^3,4 Lifetime risk of suicide in bipolar disorder is approximately 20 times that in the general population.⁵

Although Ms. R’s history does not reveal a previous manic episode, ruling out hypomania is difficult because it usually does not impair work or social functioning. Hypomania often goes unreported because others hardly notice it. Collateral history can uncover clues to hypomania (See For Your Patient), but Ms. R’s husband and daughters say they have not seen such episodes.

On the other hand, normal behavior can be mistaken for hypomania. Ms. R’s previous psychiatrist and primary care physician might have misinterpreted Ms. R’s baseline extroverted personality as hypomanic behavior. Also, her over-whelming depressive and anxiety symptoms between depressive episodes made her normal moods appear hypomanic.

Compared with unipolar depression, bipolar depression is more frequently associated with psychomotor retardation, hypersomnia, early onset, and family history of bipolar disorder.⁶ Ms. R, however, suffered low energy, terminal insomnia, and late onset, and had no known family history of bipolar disorder.

The Mood Disorder Questionnaire, a scale of self-administered questions, can help screen for symptoms that suggest bipolar disorder. A positive questionnaire result demands further clinical evaluation.⁷

Box

Continued treatment: ‘normal’ again

In addition to the HAM-D, we also administer the Mood Disorder Questionnaire. Results suggest Ms. R does not have bipolar illness.

To address Ms. R’s depressive symptoms, we start the selective serotonin reuptake inhibitor escitalopram at a low dosage (5 mg/d) to avoid exacerbating her anxiety. We discuss the drug’s potential to induce mania, hypomania, or other adverse effects such as nausea, anxiety, sleep disturbance, headache, and sexual dysfunction. Buspirone is maintained at 15 mg bid.

Two weeks later, Ms. R reports some increase in energy and motivation. After another 2 weeks, she reports significantly improved mood and concentration. She consistently falls asleep at 10 PM and sleeps 8 hours each night. She also finds time to read and go out with her friends and she gets along more amicably with her daughters and husband.

One month later, we increase escitalopram to 10 mg/d, a normal therapeutic dosage. Ms. R continues to respond positively and reports no side effects. Two months after starting the antidepressant, her HAM-D score of 8 suggests normal mood. We decrease follow-up visits to once monthly.

At a subsequent visit, Ms. R tells us she wants to find a job. A month later, she says she is enjoying her new job in a department store. Over the next 6 months, she remains free of anxiety, depressive symptoms, hypomanic behavior, and side effects. She tells us it’s nice to feel “normal” again.

We reduce Ms. R’s appointments to every 3 months. After another year, we refer her back to her primary care physician at her request.

The authors’ observations

DSM-IV-TR¹ divides bipolar disorder into three categories:

• type I, in which the patient has had at least one manic episode with or without major depression
• type II, characterized by one or more major depressive episodes and at least one hypomanic episode
• cyclothymia, which is defined as fluctuation between hypomanic and minor depressive episodes.

Much is said about how underdiagnosis of bipolar disorder⁸ delays or prevents proper therapy with mood stabilizers, leading to suboptimal symptom resolution. As with Ms. R, however, an incorrect bipolar disorder diagnosis can be just as harmful. Three years of unnecessary and ineffective treatment worsened her anxiety and depressive symptoms and quality of life.

A comprehensive clinical interview supplemented with insights from family and friends can minimize the risk of misdiagnosis when patients present with symptoms that suggest bipolar disorder, depression, or GAD.

Differentiating between the following clinical features can also help you reach a diagnosis:

Sleep/energy level. Mania/hypomania is characterized by decreased need for sleep; patients often feel energetic even after 2 to 4 hours of sleep. Both depression and GAD diminish energy level, although mood is more depressed in depression. Patients with GAD have trouble falling asleep, while those with depression awaken early or have hypersomnia.

Behavior. Patients in the manic phase of bipolar disorder engage in risky, pleasurable activities with high potential for painful consequences. This drastic behavior change is not seen in depression or GAD (Table 2).

Table 2

Differentiating symptoms common to GAD, major depression, and mania

Related resources

• Depression and Bipolar Support Alliance. www.dbsalliance.org.
• Anxiety Disorders Association of America. www.adaa.org.

Drug brand names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Quetiapine • Seroquel
• Valproic acid • Depakene
• Venlafaxine • Effexor

Disclosures

Dr. Williams is a speaker for Wyeth.

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

History: ‘A zillion racing thoughts’

Ms. R, age 44, is referred by her primary care physician. She complains of tenseness, irritability, avolition, and fatigue. She worries incessantly that her children will get sick, a catastrophe will befall her husband, or she’ll do something wrong. She says she sometimes feels as if she’s thinking “a zillion racing thoughts.”

Once fun-loving, outgoing, and energetic, Ms. R says she began feeling unusually anxious 3 years ago. A psychiatrist diagnosed bipolar disorder type II based on her racing thoughts, irritability, low energy, and history of mood swings. Over 2 years, the psychiatrist tried combining valproic acid with bupropion, citalopram, or extended-release venlafaxine, then tried lithium monotherapy. Nothing worked.

Frustrated, Ms. R left the psychiatrist and consulted her primary care physician, who prescribed gabapentin, 200 mg each morning and 300 mg at night; fluoxetine, 50 mg/d; and quetiapine, 12.5 mg/d. Ms. R noticed no improvement and stopped the medications after 6 weeks. The physician urged her to see another psychiatrist, and she presented to us 2 weeks after stopping the medications.

Ms. R also has been feeling depressed and irritable the past 4 months and has trouble falling and staying asleep at night. She sleeps 4 to 5 hours nightly, constantly feels tired, cannot concentrate, and overeats to try to alleviate her stress. She has gained 6 pounds over 2 to 3 months and weighs 160 lb; her body mass index of 26 indicates she is overweight.

She says her worries overwhelm her and cause heart palpitations and muscle tension in her neck and shoulders. She admits to feeling “worthless,” but denies suicidal thoughts.

Ms. R describes her husband and two teenage daughters as “very supportive,” but admits that her fatigue and irritability have strained these relationships; she says she snaps at them for minor things, such as coming to dinner 1 minute late. She misses her job, which she recently quit because of her decreasing ability to function.

At intake, Ms. R says she will not resume previous medications but will consider alternatives. She refuses psychotherapy because of time constraints and transportation problems but is willing to return every 2 weeks for medication checks. She says she adhered to every prescription over 3 years with no major side effects. She has never taken an antidepressant or anxiolytic without a mood stabilizer.

Ms. R reports no medical problems, past substance use, current or past psychotic symptoms, or psychiatric hospitalizations. Her family history shows depression in one first-degree relative and anxiety in others. Her Hamilton Anxiety Scale (HAM-A) score of 20 indicates moderate anxiety. Laboratory tests ordered by her primary care physician are normal.

poll here

The authors’ observations

Racing thoughts, irritable mood, decreased sleep, and concentration problems can point to GAD, mania associated with bipolar disorder type I, or hypomania suggesting bipolar disorder type I or II (Table 1).¹

We suspect GAD because:

• Ms. R’s thoughts “race” only when she worries
• her irritability and concentration problems seem more sustained than episodic
• she has difficulty falling and staying asleep, but her need for sleep has not decreased
• she complains of constant fatigue, whereas abnormally high energy characterizes bipolar disorder’s manic or hypomanic phase.

Does Ms. R have depression? Determining if the patient’s depressive symptoms are secondary to GAD or warrant a separate diagnosis can be difficult (Table 1). With Ms. R’s permission, we talked to her family, because collateral information often helps clarify the diagnosis. Her husband and daughters offered no significant new insights, however.

Table 1

Overlap among symptoms that suggest GAD, mania, or major depression

Treatment: Targeting the anxiety

To address Ms. R’s anxiety symptoms, we start buspirone, 5 mg tid, and titrate to 15 mg bid over 2 weeks. We choose buspirone—which is FDA-approved to treat GAD—because it is unlikely to cause a mood switch if bipolar disorder is causing Ms. R’s depression. We discuss with her the drug’s indications, benefits, and potential side effects (such as vertigo, headache, lightheadedness, and nausea).

At the first 2-week follow-up, Ms. R reports no side effects but little improvement. After another 2 weeks, she says she feels less anxiety, irritability, pain, and fewer racing thoughts. She reports less difficulty falling asleep, though she’s still sleeping only about 6 hours nightly. Her HAM-A score falls to 12, indicating mild anxiety.

Ms. R, however, says she still feels depressed, tired, distracted, unmotivated, and worthless. Her Hamilton Rating Scale for Depression (HAM-D) score of 16 indicates moderate depression.

poll here

The authors’ observations

The persistence of Ms. R’s depressive symptoms suggests comorbid major depressive disorder (MDD). In fact, MDD and GAD are considered the most common mood-anxiety comorbidities.²

Determining whether Ms. R has unipolar depression or bipolar disorder is extremely important, considering the treatment implications. In patients with bipolar disorder, any antidepressant can trigger mania or hypomania if used without a mood stabilizer. Some studies also have associated rare cases of suicidal behavior with antidepressant use.^3,4 Lifetime risk of suicide in bipolar disorder is approximately 20 times that in the general population.⁵

Although Ms. R’s history does not reveal a previous manic episode, ruling out hypomania is difficult because it usually does not impair work or social functioning. Hypomania often goes unreported because others hardly notice it. Collateral history can uncover clues to hypomania (See For Your Patient), but Ms. R’s husband and daughters say they have not seen such episodes.

On the other hand, normal behavior can be mistaken for hypomania. Ms. R’s previous psychiatrist and primary care physician might have misinterpreted Ms. R’s baseline extroverted personality as hypomanic behavior. Also, her over-whelming depressive and anxiety symptoms between depressive episodes made her normal moods appear hypomanic.

Compared with unipolar depression, bipolar depression is more frequently associated with psychomotor retardation, hypersomnia, early onset, and family history of bipolar disorder.⁶ Ms. R, however, suffered low energy, terminal insomnia, and late onset, and had no known family history of bipolar disorder.

The Mood Disorder Questionnaire, a scale of self-administered questions, can help screen for symptoms that suggest bipolar disorder. A positive questionnaire result demands further clinical evaluation.⁷

Box

Continued treatment: ‘normal’ again

In addition to the HAM-D, we also administer the Mood Disorder Questionnaire. Results suggest Ms. R does not have bipolar illness.

To address Ms. R’s depressive symptoms, we start the selective serotonin reuptake inhibitor escitalopram at a low dosage (5 mg/d) to avoid exacerbating her anxiety. We discuss the drug’s potential to induce mania, hypomania, or other adverse effects such as nausea, anxiety, sleep disturbance, headache, and sexual dysfunction. Buspirone is maintained at 15 mg bid.

Two weeks later, Ms. R reports some increase in energy and motivation. After another 2 weeks, she reports significantly improved mood and concentration. She consistently falls asleep at 10 PM and sleeps 8 hours each night. She also finds time to read and go out with her friends and she gets along more amicably with her daughters and husband.

One month later, we increase escitalopram to 10 mg/d, a normal therapeutic dosage. Ms. R continues to respond positively and reports no side effects. Two months after starting the antidepressant, her HAM-D score of 8 suggests normal mood. We decrease follow-up visits to once monthly.

At a subsequent visit, Ms. R tells us she wants to find a job. A month later, she says she is enjoying her new job in a department store. Over the next 6 months, she remains free of anxiety, depressive symptoms, hypomanic behavior, and side effects. She tells us it’s nice to feel “normal” again.

We reduce Ms. R’s appointments to every 3 months. After another year, we refer her back to her primary care physician at her request.

The authors’ observations

DSM-IV-TR¹ divides bipolar disorder into three categories:

• type I, in which the patient has had at least one manic episode with or without major depression
• type II, characterized by one or more major depressive episodes and at least one hypomanic episode
• cyclothymia, which is defined as fluctuation between hypomanic and minor depressive episodes.

Much is said about how underdiagnosis of bipolar disorder⁸ delays or prevents proper therapy with mood stabilizers, leading to suboptimal symptom resolution. As with Ms. R, however, an incorrect bipolar disorder diagnosis can be just as harmful. Three years of unnecessary and ineffective treatment worsened her anxiety and depressive symptoms and quality of life.

A comprehensive clinical interview supplemented with insights from family and friends can minimize the risk of misdiagnosis when patients present with symptoms that suggest bipolar disorder, depression, or GAD.

Differentiating between the following clinical features can also help you reach a diagnosis:

Sleep/energy level. Mania/hypomania is characterized by decreased need for sleep; patients often feel energetic even after 2 to 4 hours of sleep. Both depression and GAD diminish energy level, although mood is more depressed in depression. Patients with GAD have trouble falling asleep, while those with depression awaken early or have hypersomnia.

Behavior. Patients in the manic phase of bipolar disorder engage in risky, pleasurable activities with high potential for painful consequences. This drastic behavior change is not seen in depression or GAD (Table 2).

Table 2

Differentiating symptoms common to GAD, major depression, and mania

Related resources

• Depression and Bipolar Support Alliance. www.dbsalliance.org.
• Anxiety Disorders Association of America. www.adaa.org.

Drug brand names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Quetiapine • Seroquel
• Valproic acid • Depakene
• Venlafaxine • Effexor

Disclosures

Dr. Williams is a speaker for Wyeth.

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

History: ‘A zillion racing thoughts’

Ms. R, age 44, is referred by her primary care physician. She complains of tenseness, irritability, avolition, and fatigue. She worries incessantly that her children will get sick, a catastrophe will befall her husband, or she’ll do something wrong. She says she sometimes feels as if she’s thinking “a zillion racing thoughts.”

Once fun-loving, outgoing, and energetic, Ms. R says she began feeling unusually anxious 3 years ago. A psychiatrist diagnosed bipolar disorder type II based on her racing thoughts, irritability, low energy, and history of mood swings. Over 2 years, the psychiatrist tried combining valproic acid with bupropion, citalopram, or extended-release venlafaxine, then tried lithium monotherapy. Nothing worked.

Frustrated, Ms. R left the psychiatrist and consulted her primary care physician, who prescribed gabapentin, 200 mg each morning and 300 mg at night; fluoxetine, 50 mg/d; and quetiapine, 12.5 mg/d. Ms. R noticed no improvement and stopped the medications after 6 weeks. The physician urged her to see another psychiatrist, and she presented to us 2 weeks after stopping the medications.

Ms. R also has been feeling depressed and irritable the past 4 months and has trouble falling and staying asleep at night. She sleeps 4 to 5 hours nightly, constantly feels tired, cannot concentrate, and overeats to try to alleviate her stress. She has gained 6 pounds over 2 to 3 months and weighs 160 lb; her body mass index of 26 indicates she is overweight.

She says her worries overwhelm her and cause heart palpitations and muscle tension in her neck and shoulders. She admits to feeling “worthless,” but denies suicidal thoughts.

Ms. R describes her husband and two teenage daughters as “very supportive,” but admits that her fatigue and irritability have strained these relationships; she says she snaps at them for minor things, such as coming to dinner 1 minute late. She misses her job, which she recently quit because of her decreasing ability to function.

At intake, Ms. R says she will not resume previous medications but will consider alternatives. She refuses psychotherapy because of time constraints and transportation problems but is willing to return every 2 weeks for medication checks. She says she adhered to every prescription over 3 years with no major side effects. She has never taken an antidepressant or anxiolytic without a mood stabilizer.

Ms. R reports no medical problems, past substance use, current or past psychotic symptoms, or psychiatric hospitalizations. Her family history shows depression in one first-degree relative and anxiety in others. Her Hamilton Anxiety Scale (HAM-A) score of 20 indicates moderate anxiety. Laboratory tests ordered by her primary care physician are normal.

poll here

The authors’ observations

Racing thoughts, irritable mood, decreased sleep, and concentration problems can point to GAD, mania associated with bipolar disorder type I, or hypomania suggesting bipolar disorder type I or II (Table 1).¹

We suspect GAD because:

• Ms. R’s thoughts “race” only when she worries
• her irritability and concentration problems seem more sustained than episodic
• she has difficulty falling and staying asleep, but her need for sleep has not decreased
• she complains of constant fatigue, whereas abnormally high energy characterizes bipolar disorder’s manic or hypomanic phase.

Does Ms. R have depression? Determining if the patient’s depressive symptoms are secondary to GAD or warrant a separate diagnosis can be difficult (Table 1). With Ms. R’s permission, we talked to her family, because collateral information often helps clarify the diagnosis. Her husband and daughters offered no significant new insights, however.

Table 1

Overlap among symptoms that suggest GAD, mania, or major depression

Treatment: Targeting the anxiety

To address Ms. R’s anxiety symptoms, we start buspirone, 5 mg tid, and titrate to 15 mg bid over 2 weeks. We choose buspirone—which is FDA-approved to treat GAD—because it is unlikely to cause a mood switch if bipolar disorder is causing Ms. R’s depression. We discuss with her the drug’s indications, benefits, and potential side effects (such as vertigo, headache, lightheadedness, and nausea).

At the first 2-week follow-up, Ms. R reports no side effects but little improvement. After another 2 weeks, she says she feels less anxiety, irritability, pain, and fewer racing thoughts. She reports less difficulty falling asleep, though she’s still sleeping only about 6 hours nightly. Her HAM-A score falls to 12, indicating mild anxiety.

Ms. R, however, says she still feels depressed, tired, distracted, unmotivated, and worthless. Her Hamilton Rating Scale for Depression (HAM-D) score of 16 indicates moderate depression.

poll here

The authors’ observations

The persistence of Ms. R’s depressive symptoms suggests comorbid major depressive disorder (MDD). In fact, MDD and GAD are considered the most common mood-anxiety comorbidities.²

Determining whether Ms. R has unipolar depression or bipolar disorder is extremely important, considering the treatment implications. In patients with bipolar disorder, any antidepressant can trigger mania or hypomania if used without a mood stabilizer. Some studies also have associated rare cases of suicidal behavior with antidepressant use.^3,4 Lifetime risk of suicide in bipolar disorder is approximately 20 times that in the general population.⁵

Although Ms. R’s history does not reveal a previous manic episode, ruling out hypomania is difficult because it usually does not impair work or social functioning. Hypomania often goes unreported because others hardly notice it. Collateral history can uncover clues to hypomania (See For Your Patient), but Ms. R’s husband and daughters say they have not seen such episodes.

On the other hand, normal behavior can be mistaken for hypomania. Ms. R’s previous psychiatrist and primary care physician might have misinterpreted Ms. R’s baseline extroverted personality as hypomanic behavior. Also, her over-whelming depressive and anxiety symptoms between depressive episodes made her normal moods appear hypomanic.

Compared with unipolar depression, bipolar depression is more frequently associated with psychomotor retardation, hypersomnia, early onset, and family history of bipolar disorder.⁶ Ms. R, however, suffered low energy, terminal insomnia, and late onset, and had no known family history of bipolar disorder.

The Mood Disorder Questionnaire, a scale of self-administered questions, can help screen for symptoms that suggest bipolar disorder. A positive questionnaire result demands further clinical evaluation.⁷

Box

Continued treatment: ‘normal’ again

In addition to the HAM-D, we also administer the Mood Disorder Questionnaire. Results suggest Ms. R does not have bipolar illness.

To address Ms. R’s depressive symptoms, we start the selective serotonin reuptake inhibitor escitalopram at a low dosage (5 mg/d) to avoid exacerbating her anxiety. We discuss the drug’s potential to induce mania, hypomania, or other adverse effects such as nausea, anxiety, sleep disturbance, headache, and sexual dysfunction. Buspirone is maintained at 15 mg bid.

Two weeks later, Ms. R reports some increase in energy and motivation. After another 2 weeks, she reports significantly improved mood and concentration. She consistently falls asleep at 10 PM and sleeps 8 hours each night. She also finds time to read and go out with her friends and she gets along more amicably with her daughters and husband.

One month later, we increase escitalopram to 10 mg/d, a normal therapeutic dosage. Ms. R continues to respond positively and reports no side effects. Two months after starting the antidepressant, her HAM-D score of 8 suggests normal mood. We decrease follow-up visits to once monthly.

At a subsequent visit, Ms. R tells us she wants to find a job. A month later, she says she is enjoying her new job in a department store. Over the next 6 months, she remains free of anxiety, depressive symptoms, hypomanic behavior, and side effects. She tells us it’s nice to feel “normal” again.

We reduce Ms. R’s appointments to every 3 months. After another year, we refer her back to her primary care physician at her request.

The authors’ observations

DSM-IV-TR¹ divides bipolar disorder into three categories:

• type I, in which the patient has had at least one manic episode with or without major depression
• type II, characterized by one or more major depressive episodes and at least one hypomanic episode
• cyclothymia, which is defined as fluctuation between hypomanic and minor depressive episodes.

Much is said about how underdiagnosis of bipolar disorder⁸ delays or prevents proper therapy with mood stabilizers, leading to suboptimal symptom resolution. As with Ms. R, however, an incorrect bipolar disorder diagnosis can be just as harmful. Three years of unnecessary and ineffective treatment worsened her anxiety and depressive symptoms and quality of life.

A comprehensive clinical interview supplemented with insights from family and friends can minimize the risk of misdiagnosis when patients present with symptoms that suggest bipolar disorder, depression, or GAD.

Differentiating between the following clinical features can also help you reach a diagnosis:

Sleep/energy level. Mania/hypomania is characterized by decreased need for sleep; patients often feel energetic even after 2 to 4 hours of sleep. Both depression and GAD diminish energy level, although mood is more depressed in depression. Patients with GAD have trouble falling asleep, while those with depression awaken early or have hypersomnia.

Behavior. Patients in the manic phase of bipolar disorder engage in risky, pleasurable activities with high potential for painful consequences. This drastic behavior change is not seen in depression or GAD (Table 2).

Table 2

Differentiating symptoms common to GAD, major depression, and mania

Related resources

• Depression and Bipolar Support Alliance. www.dbsalliance.org.
• Anxiety Disorders Association of America. www.adaa.org.

Drug brand names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Quetiapine • Seroquel
• Valproic acid • Depakene
• Venlafaxine • Effexor

Disclosures

Dr. Williams is a speaker for Wyeth.

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

History: Suddenly Speechless

Mr. P, age 52, is transferred to our behavioral health unit after 1 month of unsuccessful treatment at a psychiatric hospital. He is mute and disheveled with blunted affect.

Before his hospitalization, Mr. P—who is mildly retarded and has an IQ of 67—lived independently, managed his finances, held two part-time jobs, volunteered as an usher at church, and had a girlfriend. He has been medically stable with diagnoses of indolent stage-zero chronic lymphocytic leukemia (for which he took no medication), moderate obesity, and essential hypertension. For 2 years he has been taking reserpine, 0.25 mg/d, for hypertension, and weighs 200 lb at presentation (body mass index: 29 kg/m²). He has no history of mental illness.

Seven months ago, Mr. P began having trouble dressing and bathing. He also began eating considerably less—about one-third of his normal food intake—and lost 20 lbs over 6 months.

Mr. P also began standing in the street for hours at a time—calling out to passers-by that people were dying and he was causing their deaths—until family members persuaded him to return home. He was not hallucinating, but his brother—who is Mr. P’s legal guardian—said symptoms worsened after a family friend died. After Mr. P became mute, resistant to direction, and immobile, his brother got him admitted to the psychiatric hospital.

The attending physician stopped reserpine—which might cause depression—and started hydrochlorothiazide, 25 mg/d, to maintain normal blood pressure. A psychiatrist diagnosed major depressive disorder and psychosis not otherwise specified, and prescribed mirtazapine, 30 mg nightly, and quetiapine, 25 mg bid. The psychiatrist ruled out lethal catatonia, as vital signs remained stable. When Mr. P’s symptoms did not improve after 1 month, the psychiatrist recommended electroconvulsive therapy (ECT) and transferred him to our facility.

Physical examination and laboratory findings are normal except for lymphocytosis secondary to leukemia:

poll here

The authors’ observations

Mr. P. has major depression with psychotic features. His staring, catalepsy, negativism, selective mutism, and posturing indicate catatonia, and his nihilistic delusions signal Cotard’s syndrome, a delusional depressive disorder.

Catatonia consists of changes in muscle tone and activity and is accompanied by echopraxia and echolalia. Many medical conditions or medications can cause catatonia (Table 1).¹ Resultant immobility and stupor can lead to contractures, pressure ulcers, venous thrombosis, and pulmonary emboli. Refusal to eat or drink can cause malnutrition, dehydration, weight loss, and muscle wasting. Approximately 9% of psychiatric inpatients develop catatonia at some point.²

DSM-IV-TR³ describes catatonia criteria as specifiers in affective illness and requires two or more of the following features for diagnosis:

• catalepsy or stupor
  
• purposeless, excessive motor activity
  
• negativism or mutism
  
• peculiar voluntary behaviors, such as posturing, stereotypy, or mannerisms
  
• echolalia or echopraxia (Table 2).
  

Catatonia can occur during an excited or retarded state:

• Excited catatonia—also called delirious mania or an oneiroid state—is marked by a dreamlike sensorium, rapid onset, confabulation, derealization, depersonalization, disorientation, and a mixture of catatonic features.⁴
  
• Retarded catatonia can be diagnosed using DSM-IV-TR criteria for catatonia. In mild cases or early in presentation, symptoms resemble anergy and psychomotor slowing typical of depression.
  

Table 1

Recognized causes of catatonia

Catatonia: Defining clinical characteristics

Cotard’s syndrome, first described in the late 1800s by French neurologist Jules Cotard, can accompany folie à deux⁷ or lycanthropy, the delusional belief that one has been transformed into a werewolf.⁸ In rare cases, patients believe that their bodies are abnormally enlarged.⁷ Cotard’s syndrome can exist alone or as part of a psychiatric illness with nihilistic delusions.⁷

poll hereTable 3

Characteristics of Cotard’s syndrome

The authors’ observations

Mr. P.’s episode appears to have been idiopathic.

Reserpine could have caused his decompensation, though precisely how is unclear. The medication is alleged to cause depression by depleting serotonin, dopamine, and norepinephrine, but some researchers believe it exacerbates pre-existing depression.^9,10

When treating any patient with a history of depression, find out if he or she is taking reserpine. Advise the primary care physician to discontinue the drug if the patient is self-deprecating or despondent, or reports early morning insomnia, loss of appetite, or impotence.¹¹

Treatment: False Start

To address Mr. P’s catatonia, we stop quetiapine and mirtazapine and start IM lorazepam, 2 mg qid. After 4 days his condition is stable, but he still believes that he and everyone else is dead.

poll here

The authors’ observations

Parenteral benzodiazepines typically are used to treat patients with catatonia and Cotard’s syndrome while the clinician searches for a toxic or medical cause. Most patients with nonemergent catatonia respond to a benzodiazepine.¹²

Although opinion differs on starting dosages of IM lorazepam in retarded catatonia, we recommend 2 mg IM and repeat doses every 3 hours if the patient does not respond.^4,13 Lack of response after 20 mg (10 doses) warrants ECT.⁴

Consider ECT—which has shown effectiveness for treating both catatonia and Cotard’s syndrome in case reports^6-8,14,15—as first-line treatment in emergent catatonia. Do not try a first- or second-generation neuroleptic, which can worsen clinical outcome.

Treatment: a Three-Week Trial

We receive informed consent from Mr. P’s brother to try 10 ECT treatments over 3 weeks. We choose left anterior right temporal electrode placement to minimize cognitive interference,¹⁶ and give Mr. P glycopyrrolate, 0.2 mg before each treatment, to manage bradycardia resulting from enhanced vagal tone after electrical stimulation. According to ECT protocol, we administer the anesthetic methohexital, 0.75 to 1.0 mg/kg, and the muscle relaxant succinylcholine, 0.5 to 1 mg/kg, to shorten seizure duration during ECT.

Mr. P also receives forced ventilation at each treatment to counteract brief succinylcholine-induced paralysis of the diaphragm and other muscle tissue. Stimulus intensity begins at 35% and is increased to 50% as the patient’s seizure threshold increases. Each morning, Mr. P also receives extended-release venlafaxine, 225 mg, for depressive symptoms, and hydrochlorothiazide, 25 mg.

After the first ECT treatment, Mr. P’s affect starts to brighten. He speaks a few words after the third treatment and begins eating larger portions by the fifth treatment. After the last treatment, he is performing activities of daily living, talking readily and coherently, and playing basketball with peers. He shows no adverse cognitive effects or other complications from ECT.

The authors’ observations

Although little evidence guides treatment of catatonia in the developmentally disabled,¹⁷ we support early use of ECT in those with serious refractory mental illness.¹⁸ Some clinicians hesitate to administer ECT to patients with mental retardation because they might be particularly vulnerable to adverse medication effects.¹⁹ ECT, however, has been found to cause minimal side effects in this population²⁰ and does not cause or exacerbate brain damage.²¹

If the patient is mentally incapable of consenting to ECT, obtain informed consent from his or her legal guardian.

Conclusion: Leaving the Hospital

We discharge Mr. P after 25 days. He shows no evidence of psychosis, suicidality, or intent to harm others. He continues hydrochlorothiazide and venlafaxine at the same dosages. He returns home with his brother, and 6 months later is functioning well.

Related resources

• National Mental Health Association. Electroconvulsive therapy. www.nmha.org/infoctr/factsheets/ect.cfm.
  

• Bupropion • Wellbutrin
  
• Disulfiram • Antabuse
  
• Glycopyrrolate • Robinul
  
• Hydrochlorothiazide • Various
  
• Lorazepam • Ativan
  
• Methohexital • Brevital
  
• Mirtazapine • Remeron
  
• Quetiapine • Seroquel
  
• Reserpine • Serpasil
  
• Succinylcholine • Anectine
  
• Venlafaxine XR • Effexor XR
  

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

History: Suddenly Speechless

Mr. P, age 52, is transferred to our behavioral health unit after 1 month of unsuccessful treatment at a psychiatric hospital. He is mute and disheveled with blunted affect.

Before his hospitalization, Mr. P—who is mildly retarded and has an IQ of 67—lived independently, managed his finances, held two part-time jobs, volunteered as an usher at church, and had a girlfriend. He has been medically stable with diagnoses of indolent stage-zero chronic lymphocytic leukemia (for which he took no medication), moderate obesity, and essential hypertension. For 2 years he has been taking reserpine, 0.25 mg/d, for hypertension, and weighs 200 lb at presentation (body mass index: 29 kg/m²). He has no history of mental illness.

Seven months ago, Mr. P began having trouble dressing and bathing. He also began eating considerably less—about one-third of his normal food intake—and lost 20 lbs over 6 months.

Mr. P also began standing in the street for hours at a time—calling out to passers-by that people were dying and he was causing their deaths—until family members persuaded him to return home. He was not hallucinating, but his brother—who is Mr. P’s legal guardian—said symptoms worsened after a family friend died. After Mr. P became mute, resistant to direction, and immobile, his brother got him admitted to the psychiatric hospital.

The attending physician stopped reserpine—which might cause depression—and started hydrochlorothiazide, 25 mg/d, to maintain normal blood pressure. A psychiatrist diagnosed major depressive disorder and psychosis not otherwise specified, and prescribed mirtazapine, 30 mg nightly, and quetiapine, 25 mg bid. The psychiatrist ruled out lethal catatonia, as vital signs remained stable. When Mr. P’s symptoms did not improve after 1 month, the psychiatrist recommended electroconvulsive therapy (ECT) and transferred him to our facility.

Physical examination and laboratory findings are normal except for lymphocytosis secondary to leukemia:

poll here

The authors’ observations

Mr. P. has major depression with psychotic features. His staring, catalepsy, negativism, selective mutism, and posturing indicate catatonia, and his nihilistic delusions signal Cotard’s syndrome, a delusional depressive disorder.

Catatonia consists of changes in muscle tone and activity and is accompanied by echopraxia and echolalia. Many medical conditions or medications can cause catatonia (Table 1).¹ Resultant immobility and stupor can lead to contractures, pressure ulcers, venous thrombosis, and pulmonary emboli. Refusal to eat or drink can cause malnutrition, dehydration, weight loss, and muscle wasting. Approximately 9% of psychiatric inpatients develop catatonia at some point.²

DSM-IV-TR³ describes catatonia criteria as specifiers in affective illness and requires two or more of the following features for diagnosis:

• catalepsy or stupor
  
• purposeless, excessive motor activity
  
• negativism or mutism
  
• peculiar voluntary behaviors, such as posturing, stereotypy, or mannerisms
  
• echolalia or echopraxia (Table 2).
  

Catatonia can occur during an excited or retarded state:

• Excited catatonia—also called delirious mania or an oneiroid state—is marked by a dreamlike sensorium, rapid onset, confabulation, derealization, depersonalization, disorientation, and a mixture of catatonic features.⁴
  
• Retarded catatonia can be diagnosed using DSM-IV-TR criteria for catatonia. In mild cases or early in presentation, symptoms resemble anergy and psychomotor slowing typical of depression.
  

Table 1

Recognized causes of catatonia

Catatonia: Defining clinical characteristics

Cotard’s syndrome, first described in the late 1800s by French neurologist Jules Cotard, can accompany folie à deux⁷ or lycanthropy, the delusional belief that one has been transformed into a werewolf.⁸ In rare cases, patients believe that their bodies are abnormally enlarged.⁷ Cotard’s syndrome can exist alone or as part of a psychiatric illness with nihilistic delusions.⁷

poll hereTable 3

Characteristics of Cotard’s syndrome

The authors’ observations

Mr. P.’s episode appears to have been idiopathic.

Reserpine could have caused his decompensation, though precisely how is unclear. The medication is alleged to cause depression by depleting serotonin, dopamine, and norepinephrine, but some researchers believe it exacerbates pre-existing depression.^9,10

When treating any patient with a history of depression, find out if he or she is taking reserpine. Advise the primary care physician to discontinue the drug if the patient is self-deprecating or despondent, or reports early morning insomnia, loss of appetite, or impotence.¹¹

Treatment: False Start

To address Mr. P’s catatonia, we stop quetiapine and mirtazapine and start IM lorazepam, 2 mg qid. After 4 days his condition is stable, but he still believes that he and everyone else is dead.

poll here

The authors’ observations

Parenteral benzodiazepines typically are used to treat patients with catatonia and Cotard’s syndrome while the clinician searches for a toxic or medical cause. Most patients with nonemergent catatonia respond to a benzodiazepine.¹²

Although opinion differs on starting dosages of IM lorazepam in retarded catatonia, we recommend 2 mg IM and repeat doses every 3 hours if the patient does not respond.^4,13 Lack of response after 20 mg (10 doses) warrants ECT.⁴

Consider ECT—which has shown effectiveness for treating both catatonia and Cotard’s syndrome in case reports^6-8,14,15—as first-line treatment in emergent catatonia. Do not try a first- or second-generation neuroleptic, which can worsen clinical outcome.

Treatment: a Three-Week Trial

We receive informed consent from Mr. P’s brother to try 10 ECT treatments over 3 weeks. We choose left anterior right temporal electrode placement to minimize cognitive interference,¹⁶ and give Mr. P glycopyrrolate, 0.2 mg before each treatment, to manage bradycardia resulting from enhanced vagal tone after electrical stimulation. According to ECT protocol, we administer the anesthetic methohexital, 0.75 to 1.0 mg/kg, and the muscle relaxant succinylcholine, 0.5 to 1 mg/kg, to shorten seizure duration during ECT.

Mr. P also receives forced ventilation at each treatment to counteract brief succinylcholine-induced paralysis of the diaphragm and other muscle tissue. Stimulus intensity begins at 35% and is increased to 50% as the patient’s seizure threshold increases. Each morning, Mr. P also receives extended-release venlafaxine, 225 mg, for depressive symptoms, and hydrochlorothiazide, 25 mg.

After the first ECT treatment, Mr. P’s affect starts to brighten. He speaks a few words after the third treatment and begins eating larger portions by the fifth treatment. After the last treatment, he is performing activities of daily living, talking readily and coherently, and playing basketball with peers. He shows no adverse cognitive effects or other complications from ECT.

The authors’ observations

Although little evidence guides treatment of catatonia in the developmentally disabled,¹⁷ we support early use of ECT in those with serious refractory mental illness.¹⁸ Some clinicians hesitate to administer ECT to patients with mental retardation because they might be particularly vulnerable to adverse medication effects.¹⁹ ECT, however, has been found to cause minimal side effects in this population²⁰ and does not cause or exacerbate brain damage.²¹

If the patient is mentally incapable of consenting to ECT, obtain informed consent from his or her legal guardian.

Conclusion: Leaving the Hospital

We discharge Mr. P after 25 days. He shows no evidence of psychosis, suicidality, or intent to harm others. He continues hydrochlorothiazide and venlafaxine at the same dosages. He returns home with his brother, and 6 months later is functioning well.

Related resources

• National Mental Health Association. Electroconvulsive therapy. www.nmha.org/infoctr/factsheets/ect.cfm.
  

• Bupropion • Wellbutrin
  
• Disulfiram • Antabuse
  
• Glycopyrrolate • Robinul
  
• Hydrochlorothiazide • Various
  
• Lorazepam • Ativan
  
• Methohexital • Brevital
  
• Mirtazapine • Remeron
  
• Quetiapine • Seroquel
  
• Reserpine • Serpasil
  
• Succinylcholine • Anectine
  
• Venlafaxine XR • Effexor XR
  

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

History: Suddenly Speechless

Mr. P, age 52, is transferred to our behavioral health unit after 1 month of unsuccessful treatment at a psychiatric hospital. He is mute and disheveled with blunted affect.

Before his hospitalization, Mr. P—who is mildly retarded and has an IQ of 67—lived independently, managed his finances, held two part-time jobs, volunteered as an usher at church, and had a girlfriend. He has been medically stable with diagnoses of indolent stage-zero chronic lymphocytic leukemia (for which he took no medication), moderate obesity, and essential hypertension. For 2 years he has been taking reserpine, 0.25 mg/d, for hypertension, and weighs 200 lb at presentation (body mass index: 29 kg/m²). He has no history of mental illness.

Seven months ago, Mr. P began having trouble dressing and bathing. He also began eating considerably less—about one-third of his normal food intake—and lost 20 lbs over 6 months.

Mr. P also began standing in the street for hours at a time—calling out to passers-by that people were dying and he was causing their deaths—until family members persuaded him to return home. He was not hallucinating, but his brother—who is Mr. P’s legal guardian—said symptoms worsened after a family friend died. After Mr. P became mute, resistant to direction, and immobile, his brother got him admitted to the psychiatric hospital.

The attending physician stopped reserpine—which might cause depression—and started hydrochlorothiazide, 25 mg/d, to maintain normal blood pressure. A psychiatrist diagnosed major depressive disorder and psychosis not otherwise specified, and prescribed mirtazapine, 30 mg nightly, and quetiapine, 25 mg bid. The psychiatrist ruled out lethal catatonia, as vital signs remained stable. When Mr. P’s symptoms did not improve after 1 month, the psychiatrist recommended electroconvulsive therapy (ECT) and transferred him to our facility.

Physical examination and laboratory findings are normal except for lymphocytosis secondary to leukemia:

poll here

The authors’ observations

Mr. P. has major depression with psychotic features. His staring, catalepsy, negativism, selective mutism, and posturing indicate catatonia, and his nihilistic delusions signal Cotard’s syndrome, a delusional depressive disorder.

Catatonia consists of changes in muscle tone and activity and is accompanied by echopraxia and echolalia. Many medical conditions or medications can cause catatonia (Table 1).¹ Resultant immobility and stupor can lead to contractures, pressure ulcers, venous thrombosis, and pulmonary emboli. Refusal to eat or drink can cause malnutrition, dehydration, weight loss, and muscle wasting. Approximately 9% of psychiatric inpatients develop catatonia at some point.²

DSM-IV-TR³ describes catatonia criteria as specifiers in affective illness and requires two or more of the following features for diagnosis:

• catalepsy or stupor
  
• purposeless, excessive motor activity
  
• negativism or mutism
  
• peculiar voluntary behaviors, such as posturing, stereotypy, or mannerisms
  
• echolalia or echopraxia (Table 2).
  

Catatonia can occur during an excited or retarded state:

• Excited catatonia—also called delirious mania or an oneiroid state—is marked by a dreamlike sensorium, rapid onset, confabulation, derealization, depersonalization, disorientation, and a mixture of catatonic features.⁴
  
• Retarded catatonia can be diagnosed using DSM-IV-TR criteria for catatonia. In mild cases or early in presentation, symptoms resemble anergy and psychomotor slowing typical of depression.
  

Table 1

Recognized causes of catatonia

Catatonia: Defining clinical characteristics

Cotard’s syndrome, first described in the late 1800s by French neurologist Jules Cotard, can accompany folie à deux⁷ or lycanthropy, the delusional belief that one has been transformed into a werewolf.⁸ In rare cases, patients believe that their bodies are abnormally enlarged.⁷ Cotard’s syndrome can exist alone or as part of a psychiatric illness with nihilistic delusions.⁷

poll hereTable 3

Characteristics of Cotard’s syndrome

The authors’ observations

Mr. P.’s episode appears to have been idiopathic.

Reserpine could have caused his decompensation, though precisely how is unclear. The medication is alleged to cause depression by depleting serotonin, dopamine, and norepinephrine, but some researchers believe it exacerbates pre-existing depression.^9,10

When treating any patient with a history of depression, find out if he or she is taking reserpine. Advise the primary care physician to discontinue the drug if the patient is self-deprecating or despondent, or reports early morning insomnia, loss of appetite, or impotence.¹¹

Treatment: False Start

To address Mr. P’s catatonia, we stop quetiapine and mirtazapine and start IM lorazepam, 2 mg qid. After 4 days his condition is stable, but he still believes that he and everyone else is dead.

poll here

The authors’ observations

Parenteral benzodiazepines typically are used to treat patients with catatonia and Cotard’s syndrome while the clinician searches for a toxic or medical cause. Most patients with nonemergent catatonia respond to a benzodiazepine.¹²

Although opinion differs on starting dosages of IM lorazepam in retarded catatonia, we recommend 2 mg IM and repeat doses every 3 hours if the patient does not respond.^4,13 Lack of response after 20 mg (10 doses) warrants ECT.⁴

Consider ECT—which has shown effectiveness for treating both catatonia and Cotard’s syndrome in case reports^6-8,14,15—as first-line treatment in emergent catatonia. Do not try a first- or second-generation neuroleptic, which can worsen clinical outcome.

Treatment: a Three-Week Trial

We receive informed consent from Mr. P’s brother to try 10 ECT treatments over 3 weeks. We choose left anterior right temporal electrode placement to minimize cognitive interference,¹⁶ and give Mr. P glycopyrrolate, 0.2 mg before each treatment, to manage bradycardia resulting from enhanced vagal tone after electrical stimulation. According to ECT protocol, we administer the anesthetic methohexital, 0.75 to 1.0 mg/kg, and the muscle relaxant succinylcholine, 0.5 to 1 mg/kg, to shorten seizure duration during ECT.

Mr. P also receives forced ventilation at each treatment to counteract brief succinylcholine-induced paralysis of the diaphragm and other muscle tissue. Stimulus intensity begins at 35% and is increased to 50% as the patient’s seizure threshold increases. Each morning, Mr. P also receives extended-release venlafaxine, 225 mg, for depressive symptoms, and hydrochlorothiazide, 25 mg.

After the first ECT treatment, Mr. P’s affect starts to brighten. He speaks a few words after the third treatment and begins eating larger portions by the fifth treatment. After the last treatment, he is performing activities of daily living, talking readily and coherently, and playing basketball with peers. He shows no adverse cognitive effects or other complications from ECT.

The authors’ observations

Although little evidence guides treatment of catatonia in the developmentally disabled,¹⁷ we support early use of ECT in those with serious refractory mental illness.¹⁸ Some clinicians hesitate to administer ECT to patients with mental retardation because they might be particularly vulnerable to adverse medication effects.¹⁹ ECT, however, has been found to cause minimal side effects in this population²⁰ and does not cause or exacerbate brain damage.²¹

If the patient is mentally incapable of consenting to ECT, obtain informed consent from his or her legal guardian.

Conclusion: Leaving the Hospital

We discharge Mr. P after 25 days. He shows no evidence of psychosis, suicidality, or intent to harm others. He continues hydrochlorothiazide and venlafaxine at the same dosages. He returns home with his brother, and 6 months later is functioning well.

Related resources

• National Mental Health Association. Electroconvulsive therapy. www.nmha.org/infoctr/factsheets/ect.cfm.
  

• Bupropion • Wellbutrin
  
• Disulfiram • Antabuse
  
• Glycopyrrolate • Robinul
  
• Hydrochlorothiazide • Various
  
• Lorazepam • Ativan
  
• Methohexital • Brevital
  
• Mirtazapine • Remeron
  
• Quetiapine • Seroquel
  
• Reserpine • Serpasil
  
• Succinylcholine • Anectine
  
• Venlafaxine XR • Effexor XR
  

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

History: ‘They’re making me crazy’

Ms. D, age 22, is brought to the emergency room by her older brother for psychiatric evaluation after a family argument. He tells us that his sister is out most nights, hanging out at nightclubs. When she’s home, he says, she locks herself in her room and avoids him and his younger brother, who also lives with them.

Recently, her brother says, Ms. D signed a contract to appear in pornographic videos. When he found out, he went to the studio’s producer and nullified the contract.

Ms. D, frustrated with her brother’s interference, tells us she dreams of becoming a movie star and going to college, but blames him for “holding me back” and keeping her unemployed.

Worse, she says, he and her two sisters are impostors who are “trying to hurt me” and are “making me go crazy.” She fears her “false brother” will take her house if she leaves, yet she feels unsafe at home because strangers—envious of “my beauty and intelligence”—peek into her windows and stalk her. She tells us her father is near and guards her—even though he died 4 years ago.

Ms. D, who lost her mother at age 2, began having psychotic episodes at age 19, a few months after her father’s death. At that time, she was hospitalized after insisting that her father had faked his death because of a conspiracy against him. A hospital psychiatrist diagnosed bipolar disorder and prescribed a mood stabilizer, but she did not take the medication and her psychosis has worsened.

Ms. D’s Mini-Mental State Examination score of 30 indicates that she is neither grossly confused nor has underlying dementia. However, she is emotionally labile with grossly disorganized thought processes and paranoid and grandiose delusions.

We could not locate other family members, so Ms. D’s family psychiatric history is unknown. She has casual relationships with men but does not have a boyfriend. She acknowledges that she frequents local nightclubs but denies using alcohol.

Blood work and other medical examination results are normal. Negative urine toxicology screen suggests she not abusing substances, and electrolytes and thyroid-stimulating hormone levels are normal. Negative rapid plasma reagin rules out tertiary syphilis. We do not order radiologic studies because her presentation does not suggest focal abnormality, and neurologic exam results are benign.

poll here

The authors’ observations

Patients with both paranoid delusions and manic features are challenging. Prognoses and treatment options for each group of symptoms differ substantially.

Ms. D’s grandiosity, pressured speech, tangential flight of ideas, and hypersexuality strongly suggest bipolar disorder. We could not rule out schizophrenia, however, because of her prominent hallucinations and paranoia.

Pharmacologic intoxication was not likely based on laboratory results and the longstanding, progressive course of Ms. D’s disorder. Organic pathology also was unlikely, given her normal neurologic examination and lack of other medical issues.

Treatment: Talk therapy

We tentatively diagnose Ms. D as having bipolar disorder type I with a manic episode and psychotic features. She does not meet DSM-IV-TR criteria for schizophrenia and lacks affective flattening, poverty of speech, avolition, and other negative symptoms typical of the disorder. We admit her to the inpatient psychiatric unit and prescribe lithium, 300 mg tid, and quetiapine, 50 mg bid.

An internal medicine (IM) resident visits Ms. D for 30 to 45 minutes daily during her hospitalization to check her medical status and to allow her to vent her frustration. A resident in psychiatry also interviews Ms. D for about one half-hour each day. The patient rarely interacts with other patients and speaks only with physicians and nurses.

Ms. D appears to trust the IM resident and confides in her about her brother. During their first meeting, she appears most disturbed that a man who “claims” to be her brother is sabotaging her life. She does not fear that this “impostor” will physically harm her but still distrusts him. She repeatedly reports that her late father is nearby or in the room above hers. She adds that she feels much safer in the hospital, where the “stalkers” cannot reach her.

At times, Ms. D tells the IM resident she has a twin. Other times, she believes her family is much larger than it is, and she sometimes laments that she is losing her identity. She often perseverates on Judgment Day, at which time she says her “fake” relatives will answer for their actions against her.

Ms. D’s delusions of grandiosity, tangentiality, circumferential speech, and flight of ideas persist through 4 days in the hospital. Her affect is extremely labile and occasionally inappropriate. She sometimes cries when discussing her father’s death, then stops, thinks a moment, and begins laughing. At this point, we increase lithium to 600 mg tid and quetiapine to 100 mg tid. She is suffering no side effects and infrequently requires haloperidol as a demand dose only.

poll here

The authors’ observations

A patient such as Ms. D who lives in a minimally supportive environment and has paranoid delusions could fabricate an explanation for what she perceives as family members’ incongruent behavior. She could create a reality in which these relatives are impostors.

Although this behavior is not unusual, Ms. D’s extreme reaction toward her siblings suggests Capgras syndrome, a rare misidentification disorder (Box). The syndrome is often missed in clinical practice, and its prevalence has not been quantified.

Capgras syndrome is seen most often in patients with paranoid schizophrenia—the highest functioning and most preserved schizophrenia patients. This association may indicate that both neurologic dysfunction and psychological background are necessary to produce the syndrome.

The belief that family members are impostors could point to a conspiracy theory or paranoid delusion. Ms. D’s suspicion and distrust toward her older brother indicate a paranoid state, and her other delusions—such as her belief that others are stalking her—suggest that her Capgras symptoms are another manifestation of paranoia.

Box

For Ms. D, structural brain deficits probably interacted with her psychosocial milieu to create Capgras delusions, though we did not perform confirmatory brain imaging or functional neurologic testing. Whereas right cortical lesions might impair recognition while preserving familiarity, Capgras syndrome preserves recognition but deadens the emotion that makes faces seem familiar. When focal lesions are found to cause Capgras delusion, however, the right hemisphere—specifically the frontal cortex—usually is affected.^2,3

Table

Proposed causes of Capgras syndrome

The authors’ observations

When interviewing a patient with paranoid delusions, get as much detail as possible about his or her close relationships. Try to interview one or two family members or friends. The information can help determine whether Capgras symptoms underlie paranoia.

Brain imaging might uncover pertinent abnormalities, but the cost could outweigh any benefit. No evidence supports use of CT to diagnose Capgras syndrome. Some evidence supports use of brain MRI, but more research is needed.

No specific treatment exists for Capgras delusions apart from using antipsychotics to treat the psychosis based on clinical suspicion and constellation of symptoms.

Studies have shown no difference in response to atypical antipsychotics between patients with schizophrenia and comcomitant Capgras symptoms and those with schizophrenia alone. In clinical practice, we have found that treating Capgras symptoms does improve schizophrenia’s course.

Adjunctive psychotherapy has not been studied in Capgras syndrome, and directed, insight-guided therapy might not resolve deeply rooted delusions for some patients. With Ms. D, however, “talk therapy” helped us build rapport and gave us insight into her strained familial relationships. Establishing a therapeutic alliance with the patient and encouraging healthy relationships with his or her family and friends can mitigate the effects of Capgras paranoia.

Continued treatment: Gradual change

Day by day Ms. D’s mania subsides gradually, though she still fears that a stranger posing as her brother is stalking her. She talks about her brother less frequently, though she is clearly holding fast to her delusional beliefs.

We discharge Ms. D after 10 days. Although her symptoms have not resolved, she is markedly less manic and less agitated than at admission. We arrange treatment with outpatient psychiatry. She does not follow up with her original psychiatrist and is lost to follow-up.

Related resources

• PsychNet-UK. Disorder information sheet: Capgras (delusion) syndrome. www.psychnet-uk.com/dsm_iv/capgras_syndrome.htm.
  
• Bourget D, Whitehurst L. Capgras syndrome: a review of the neurophysiological correlates and presenting clinical features in cases involving physical violence. Can J Psychiatry 2004;49:719-25. Available at: www.cpa-apc.org/Publications/Archives/CJP/2004/november/bourget.asp.
  
• Barton JJ. Disorders of face perception and recognition. Neurol Clin 2003;21:521-48.
  
• Lewis S. Brain imaging in a case of Capgras’ syndrome. Br J Psychiatry 1987;150:117-21.
  
• Christodoulou GN. The syndrome of Capgras. Br J Psychiatry 1977;130:556-64.
  

• Haloperidol • Haldol
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  

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

History: ‘They’re making me crazy’

Ms. D, age 22, is brought to the emergency room by her older brother for psychiatric evaluation after a family argument. He tells us that his sister is out most nights, hanging out at nightclubs. When she’s home, he says, she locks herself in her room and avoids him and his younger brother, who also lives with them.

Recently, her brother says, Ms. D signed a contract to appear in pornographic videos. When he found out, he went to the studio’s producer and nullified the contract.

Ms. D, frustrated with her brother’s interference, tells us she dreams of becoming a movie star and going to college, but blames him for “holding me back” and keeping her unemployed.

Worse, she says, he and her two sisters are impostors who are “trying to hurt me” and are “making me go crazy.” She fears her “false brother” will take her house if she leaves, yet she feels unsafe at home because strangers—envious of “my beauty and intelligence”—peek into her windows and stalk her. She tells us her father is near and guards her—even though he died 4 years ago.

Ms. D, who lost her mother at age 2, began having psychotic episodes at age 19, a few months after her father’s death. At that time, she was hospitalized after insisting that her father had faked his death because of a conspiracy against him. A hospital psychiatrist diagnosed bipolar disorder and prescribed a mood stabilizer, but she did not take the medication and her psychosis has worsened.

Ms. D’s Mini-Mental State Examination score of 30 indicates that she is neither grossly confused nor has underlying dementia. However, she is emotionally labile with grossly disorganized thought processes and paranoid and grandiose delusions.

We could not locate other family members, so Ms. D’s family psychiatric history is unknown. She has casual relationships with men but does not have a boyfriend. She acknowledges that she frequents local nightclubs but denies using alcohol.

Blood work and other medical examination results are normal. Negative urine toxicology screen suggests she not abusing substances, and electrolytes and thyroid-stimulating hormone levels are normal. Negative rapid plasma reagin rules out tertiary syphilis. We do not order radiologic studies because her presentation does not suggest focal abnormality, and neurologic exam results are benign.

poll here

The authors’ observations

Patients with both paranoid delusions and manic features are challenging. Prognoses and treatment options for each group of symptoms differ substantially.

Ms. D’s grandiosity, pressured speech, tangential flight of ideas, and hypersexuality strongly suggest bipolar disorder. We could not rule out schizophrenia, however, because of her prominent hallucinations and paranoia.

Pharmacologic intoxication was not likely based on laboratory results and the longstanding, progressive course of Ms. D’s disorder. Organic pathology also was unlikely, given her normal neurologic examination and lack of other medical issues.

Treatment: Talk therapy

We tentatively diagnose Ms. D as having bipolar disorder type I with a manic episode and psychotic features. She does not meet DSM-IV-TR criteria for schizophrenia and lacks affective flattening, poverty of speech, avolition, and other negative symptoms typical of the disorder. We admit her to the inpatient psychiatric unit and prescribe lithium, 300 mg tid, and quetiapine, 50 mg bid.

An internal medicine (IM) resident visits Ms. D for 30 to 45 minutes daily during her hospitalization to check her medical status and to allow her to vent her frustration. A resident in psychiatry also interviews Ms. D for about one half-hour each day. The patient rarely interacts with other patients and speaks only with physicians and nurses.

Ms. D appears to trust the IM resident and confides in her about her brother. During their first meeting, she appears most disturbed that a man who “claims” to be her brother is sabotaging her life. She does not fear that this “impostor” will physically harm her but still distrusts him. She repeatedly reports that her late father is nearby or in the room above hers. She adds that she feels much safer in the hospital, where the “stalkers” cannot reach her.

At times, Ms. D tells the IM resident she has a twin. Other times, she believes her family is much larger than it is, and she sometimes laments that she is losing her identity. She often perseverates on Judgment Day, at which time she says her “fake” relatives will answer for their actions against her.

Ms. D’s delusions of grandiosity, tangentiality, circumferential speech, and flight of ideas persist through 4 days in the hospital. Her affect is extremely labile and occasionally inappropriate. She sometimes cries when discussing her father’s death, then stops, thinks a moment, and begins laughing. At this point, we increase lithium to 600 mg tid and quetiapine to 100 mg tid. She is suffering no side effects and infrequently requires haloperidol as a demand dose only.

poll here

The authors’ observations

A patient such as Ms. D who lives in a minimally supportive environment and has paranoid delusions could fabricate an explanation for what she perceives as family members’ incongruent behavior. She could create a reality in which these relatives are impostors.

Although this behavior is not unusual, Ms. D’s extreme reaction toward her siblings suggests Capgras syndrome, a rare misidentification disorder (Box). The syndrome is often missed in clinical practice, and its prevalence has not been quantified.

Capgras syndrome is seen most often in patients with paranoid schizophrenia—the highest functioning and most preserved schizophrenia patients. This association may indicate that both neurologic dysfunction and psychological background are necessary to produce the syndrome.

The belief that family members are impostors could point to a conspiracy theory or paranoid delusion. Ms. D’s suspicion and distrust toward her older brother indicate a paranoid state, and her other delusions—such as her belief that others are stalking her—suggest that her Capgras symptoms are another manifestation of paranoia.

Box

For Ms. D, structural brain deficits probably interacted with her psychosocial milieu to create Capgras delusions, though we did not perform confirmatory brain imaging or functional neurologic testing. Whereas right cortical lesions might impair recognition while preserving familiarity, Capgras syndrome preserves recognition but deadens the emotion that makes faces seem familiar. When focal lesions are found to cause Capgras delusion, however, the right hemisphere—specifically the frontal cortex—usually is affected.^2,3

Table

Proposed causes of Capgras syndrome

The authors’ observations

When interviewing a patient with paranoid delusions, get as much detail as possible about his or her close relationships. Try to interview one or two family members or friends. The information can help determine whether Capgras symptoms underlie paranoia.

Brain imaging might uncover pertinent abnormalities, but the cost could outweigh any benefit. No evidence supports use of CT to diagnose Capgras syndrome. Some evidence supports use of brain MRI, but more research is needed.

No specific treatment exists for Capgras delusions apart from using antipsychotics to treat the psychosis based on clinical suspicion and constellation of symptoms.

Studies have shown no difference in response to atypical antipsychotics between patients with schizophrenia and comcomitant Capgras symptoms and those with schizophrenia alone. In clinical practice, we have found that treating Capgras symptoms does improve schizophrenia’s course.

Adjunctive psychotherapy has not been studied in Capgras syndrome, and directed, insight-guided therapy might not resolve deeply rooted delusions for some patients. With Ms. D, however, “talk therapy” helped us build rapport and gave us insight into her strained familial relationships. Establishing a therapeutic alliance with the patient and encouraging healthy relationships with his or her family and friends can mitigate the effects of Capgras paranoia.

Continued treatment: Gradual change

Day by day Ms. D’s mania subsides gradually, though she still fears that a stranger posing as her brother is stalking her. She talks about her brother less frequently, though she is clearly holding fast to her delusional beliefs.

We discharge Ms. D after 10 days. Although her symptoms have not resolved, she is markedly less manic and less agitated than at admission. We arrange treatment with outpatient psychiatry. She does not follow up with her original psychiatrist and is lost to follow-up.

Related resources

• PsychNet-UK. Disorder information sheet: Capgras (delusion) syndrome. www.psychnet-uk.com/dsm_iv/capgras_syndrome.htm.
  
• Bourget D, Whitehurst L. Capgras syndrome: a review of the neurophysiological correlates and presenting clinical features in cases involving physical violence. Can J Psychiatry 2004;49:719-25. Available at: www.cpa-apc.org/Publications/Archives/CJP/2004/november/bourget.asp.
  
• Barton JJ. Disorders of face perception and recognition. Neurol Clin 2003;21:521-48.
  
• Lewis S. Brain imaging in a case of Capgras’ syndrome. Br J Psychiatry 1987;150:117-21.
  
• Christodoulou GN. The syndrome of Capgras. Br J Psychiatry 1977;130:556-64.
  

• Haloperidol • Haldol
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  

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

History: ‘They’re making me crazy’

Ms. D, age 22, is brought to the emergency room by her older brother for psychiatric evaluation after a family argument. He tells us that his sister is out most nights, hanging out at nightclubs. When she’s home, he says, she locks herself in her room and avoids him and his younger brother, who also lives with them.

Recently, her brother says, Ms. D signed a contract to appear in pornographic videos. When he found out, he went to the studio’s producer and nullified the contract.

Ms. D, frustrated with her brother’s interference, tells us she dreams of becoming a movie star and going to college, but blames him for “holding me back” and keeping her unemployed.

Worse, she says, he and her two sisters are impostors who are “trying to hurt me” and are “making me go crazy.” She fears her “false brother” will take her house if she leaves, yet she feels unsafe at home because strangers—envious of “my beauty and intelligence”—peek into her windows and stalk her. She tells us her father is near and guards her—even though he died 4 years ago.

Ms. D, who lost her mother at age 2, began having psychotic episodes at age 19, a few months after her father’s death. At that time, she was hospitalized after insisting that her father had faked his death because of a conspiracy against him. A hospital psychiatrist diagnosed bipolar disorder and prescribed a mood stabilizer, but she did not take the medication and her psychosis has worsened.

Ms. D’s Mini-Mental State Examination score of 30 indicates that she is neither grossly confused nor has underlying dementia. However, she is emotionally labile with grossly disorganized thought processes and paranoid and grandiose delusions.

We could not locate other family members, so Ms. D’s family psychiatric history is unknown. She has casual relationships with men but does not have a boyfriend. She acknowledges that she frequents local nightclubs but denies using alcohol.

Blood work and other medical examination results are normal. Negative urine toxicology screen suggests she not abusing substances, and electrolytes and thyroid-stimulating hormone levels are normal. Negative rapid plasma reagin rules out tertiary syphilis. We do not order radiologic studies because her presentation does not suggest focal abnormality, and neurologic exam results are benign.

poll here

The authors’ observations

Patients with both paranoid delusions and manic features are challenging. Prognoses and treatment options for each group of symptoms differ substantially.

Ms. D’s grandiosity, pressured speech, tangential flight of ideas, and hypersexuality strongly suggest bipolar disorder. We could not rule out schizophrenia, however, because of her prominent hallucinations and paranoia.

Pharmacologic intoxication was not likely based on laboratory results and the longstanding, progressive course of Ms. D’s disorder. Organic pathology also was unlikely, given her normal neurologic examination and lack of other medical issues.

Treatment: Talk therapy

We tentatively diagnose Ms. D as having bipolar disorder type I with a manic episode and psychotic features. She does not meet DSM-IV-TR criteria for schizophrenia and lacks affective flattening, poverty of speech, avolition, and other negative symptoms typical of the disorder. We admit her to the inpatient psychiatric unit and prescribe lithium, 300 mg tid, and quetiapine, 50 mg bid.

An internal medicine (IM) resident visits Ms. D for 30 to 45 minutes daily during her hospitalization to check her medical status and to allow her to vent her frustration. A resident in psychiatry also interviews Ms. D for about one half-hour each day. The patient rarely interacts with other patients and speaks only with physicians and nurses.

Ms. D appears to trust the IM resident and confides in her about her brother. During their first meeting, she appears most disturbed that a man who “claims” to be her brother is sabotaging her life. She does not fear that this “impostor” will physically harm her but still distrusts him. She repeatedly reports that her late father is nearby or in the room above hers. She adds that she feels much safer in the hospital, where the “stalkers” cannot reach her.

At times, Ms. D tells the IM resident she has a twin. Other times, she believes her family is much larger than it is, and she sometimes laments that she is losing her identity. She often perseverates on Judgment Day, at which time she says her “fake” relatives will answer for their actions against her.

Ms. D’s delusions of grandiosity, tangentiality, circumferential speech, and flight of ideas persist through 4 days in the hospital. Her affect is extremely labile and occasionally inappropriate. She sometimes cries when discussing her father’s death, then stops, thinks a moment, and begins laughing. At this point, we increase lithium to 600 mg tid and quetiapine to 100 mg tid. She is suffering no side effects and infrequently requires haloperidol as a demand dose only.

poll here

The authors’ observations

A patient such as Ms. D who lives in a minimally supportive environment and has paranoid delusions could fabricate an explanation for what she perceives as family members’ incongruent behavior. She could create a reality in which these relatives are impostors.

Although this behavior is not unusual, Ms. D’s extreme reaction toward her siblings suggests Capgras syndrome, a rare misidentification disorder (Box). The syndrome is often missed in clinical practice, and its prevalence has not been quantified.

Capgras syndrome is seen most often in patients with paranoid schizophrenia—the highest functioning and most preserved schizophrenia patients. This association may indicate that both neurologic dysfunction and psychological background are necessary to produce the syndrome.

The belief that family members are impostors could point to a conspiracy theory or paranoid delusion. Ms. D’s suspicion and distrust toward her older brother indicate a paranoid state, and her other delusions—such as her belief that others are stalking her—suggest that her Capgras symptoms are another manifestation of paranoia.

Box

For Ms. D, structural brain deficits probably interacted with her psychosocial milieu to create Capgras delusions, though we did not perform confirmatory brain imaging or functional neurologic testing. Whereas right cortical lesions might impair recognition while preserving familiarity, Capgras syndrome preserves recognition but deadens the emotion that makes faces seem familiar. When focal lesions are found to cause Capgras delusion, however, the right hemisphere—specifically the frontal cortex—usually is affected.^2,3

Table

Proposed causes of Capgras syndrome

The authors’ observations

When interviewing a patient with paranoid delusions, get as much detail as possible about his or her close relationships. Try to interview one or two family members or friends. The information can help determine whether Capgras symptoms underlie paranoia.

Brain imaging might uncover pertinent abnormalities, but the cost could outweigh any benefit. No evidence supports use of CT to diagnose Capgras syndrome. Some evidence supports use of brain MRI, but more research is needed.

No specific treatment exists for Capgras delusions apart from using antipsychotics to treat the psychosis based on clinical suspicion and constellation of symptoms.

Studies have shown no difference in response to atypical antipsychotics between patients with schizophrenia and comcomitant Capgras symptoms and those with schizophrenia alone. In clinical practice, we have found that treating Capgras symptoms does improve schizophrenia’s course.

Adjunctive psychotherapy has not been studied in Capgras syndrome, and directed, insight-guided therapy might not resolve deeply rooted delusions for some patients. With Ms. D, however, “talk therapy” helped us build rapport and gave us insight into her strained familial relationships. Establishing a therapeutic alliance with the patient and encouraging healthy relationships with his or her family and friends can mitigate the effects of Capgras paranoia.

Continued treatment: Gradual change

Day by day Ms. D’s mania subsides gradually, though she still fears that a stranger posing as her brother is stalking her. She talks about her brother less frequently, though she is clearly holding fast to her delusional beliefs.

We discharge Ms. D after 10 days. Although her symptoms have not resolved, she is markedly less manic and less agitated than at admission. We arrange treatment with outpatient psychiatry. She does not follow up with her original psychiatrist and is lost to follow-up.

Related resources

• PsychNet-UK. Disorder information sheet: Capgras (delusion) syndrome. www.psychnet-uk.com/dsm_iv/capgras_syndrome.htm.
  
• Bourget D, Whitehurst L. Capgras syndrome: a review of the neurophysiological correlates and presenting clinical features in cases involving physical violence. Can J Psychiatry 2004;49:719-25. Available at: www.cpa-apc.org/Publications/Archives/CJP/2004/november/bourget.asp.
  
• Barton JJ. Disorders of face perception and recognition. Neurol Clin 2003;21:521-48.
  
• Lewis S. Brain imaging in a case of Capgras’ syndrome. Br J Psychiatry 1987;150:117-21.
  
• Christodoulou GN. The syndrome of Capgras. Br J Psychiatry 1977;130:556-64.
  

• Haloperidol • Haldol
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  

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

Tiberius Claudius Germanicus, age 64 and the third emperor of Rome’s Julio-Claudian dynasty, presents to you and reports, “I have severe stomach cramps. I think my wife is poisoning me, but no one believes me. I need your help.”

Retrospective diagnoses are difficult and sometimes ill-advised, but pondering the psychiatric diagnoses of historical figures can alert us to possible differential diagnoses in today’s patients. Consider this imaginary interview between Claudius and a psychiatrist, which suggests several possible diagnoses.

History: terrible royal childhood

Though born into royalty, Claudius was such a sickly infant that his family was ashamed of him and kept him out of their home. He was raised by servants. As a child, he limped and was ridiculed.

He tells you he received little formal education but had many tutors. He learned several languages and became a distinguished historian, scholar, and writer. He served in the military, both in Rome and overseas. For 13 years he has ruled the Roman Empire but fears he will soon be overthrown.

Claudius’ reign began well. He treated his freedmen advisors well, diligently attended to court proceedings, built an aqueduct, and reorganized the Roman government. Recently, however, he has ruled more eccentrically and harshly. He has ordered capricious and costly public works, such as the futile attempt to drain the 12-mile-long Fucine Lake so that the land could be farmed. He has become fond of gladiatorial games and enjoys ordering the execution of political foes. He drinks several liters of wine daily and gorges himself at imperial banquets.

This patient’s family history is complex (Box) and fraught with antisocial behavior and mental illness. Three previous marriages failed, and he describes his current wife, Agrippina, as powerful and manipulative. She has a son, Nero, from an earlier marriage. Claudius fears being poisoned by Agrippina after she instigates a relationship between Nero and Claudius’ daughter.

Box

Interview: ‘surrounded by enemies’

Claudius is uncooperative during the interview. He is irritable, tends to bark orders, smells of alcohol, stutters severely, and drools. He admits that he is depressed over myriad family problems.

He also believes that he will become a deity when he dies. He reminds you that he has the power to order executions and wonders if he should have Agrippina and her minions killed. He claims to have written 43 books and numerous historical monographs and to be the last person in the world to speak fluent Etruscan, but laments that no one appreciates his scholarly work. He says he is “surrounded by enemies” and rambles on about family intrigue, cabals, and executions.

He is oriented and shows no florid psychotic symptoms or signs of suicidality. His insight and judgment are severely impaired, and he rejects the idea that he might have a psychiatric disorder.

Claudius refuses a physical exam and abruptly terminates the interview after about 20 minutes, saying he must attend to important affairs of state.

Follow-up: claudius’ ‘last supper’

You want to get more information from family members but wonder if it is safe to do so. It becomes moot: Claudius dies one evening at dinner, days after the interview.

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The authors’ observations

Lead poisoning can cause a range of medical and neuropsychological problems, including attention deficits, antisocial behavior, and irritability.^1-4 Romans—particularly the upper class—were exposed to lead from numerous sources:

• Drinking water was contaminated because lead was used extensively to build ancient Rome’s water transportation systems.
  
• Grape juice fermented to become wine was often preserved in lead vessels, which made it sweeter. The elite drank wine more profusely than did lower-class Romans, who probably could not afford wine. Lead-sweetened grape juice was also used in delicacies eaten by the wealthy.
  
• The rich also favored expensive, lead-lined bronze bowls and plates, whereas commoners used cheap earthenware. Thus, ancient Rome’s ruling class was ingesting lead-contaminated drink and food.
  

Jerome Nriagu, a geochemist who has studied lead’s toxic effects, attributed many of Claudius’ symptoms and negative traits to lead poisoning: “He had disturbed speech, weak limbs, an ungainly gait, tremors, fits of excessive and inappropriate laughter, and unseemly anger, and he often slobbered…his contracting of plumbism would not be surprising, since he was an intemperate glutton.”⁶ Nriagu also argued that the neuropsychological sequelae of lead poisoning might have clouded the judgment of many Roman emperors.⁶

Yet some scholars, notably Robert Graves,^7,8 have argued that Claudius was highly intelligent and that his copious writing showcased his scholarly interests, hard work, and sound judgment in young adulthood. Based on Graves’ assessment, Claudius probably did not suffer severe plumbism as a child.

Birth injury or cerebral palsy might have caused Claudius’ poor gait and drooling, which were present from childhood. As his drinking and gluttony worsened later in life, alcoholism and lead poisoning could have shortened Claudius’ temper and blurred his judgment, particularly in marrying Agrippina.

Claudius’ belief that he would become a god does not strongly indicate psychosis, because his contemporaries believed that emperors could be deified after death. Opler et al,⁹ however, found that prenatal lead exposure, as suggested by elevated D-aminolevulinic acid, may be a risk factor for schizophrenia and other psychiatric disorders that manifest in late adolescence or adulthood.

Although we know little about Claudius’ medical problems, abdominal pain has a broad differential diagnosis. Poisoning at Agrippina’s hands or alcohol-induced gastritis, as well as lead-induced abdominal colic, could have caused his intolerable pain.

Bipolar disorder. Claudius’ unrestrained spending, irritability, impulsivity, grandiosity, and mood lability suggest bipolar disorder. Hypomania could have fueled his vast literary output, which has been lost. His belief that he would be deified could also be a manic symptom.

Hypomania was prevalent among Claudius’ family. Two close relatives—his nephew Caligula and great-nephew/adopted son Nero—had marked mood swings. These two emperors were more antisocial than Claudius and showed behavior more consistent with frank mania.

Caligula, who preceded Claudius as emperor, was well known for his excessive behaviors. He was vicious and promiscuous, having sex in public with men, wives of others, and his sisters. Most famously, he considered making his horse, Incitatus, a consul. He gave this horse a “marble stable…a house and a household of slaves and furniture.”¹⁰

Nero, who succeeded Claudius, was an alcoholic who frequently indulged his appetites. He believed he was a great singer and became infamous for playing his fiddle while Rome burned. Some of his last words are supposed to have been, “What an artist dies with me!”¹⁰

Alcoholism. Some historians have estimated that two-thirds of Roman emperors who reigned from 30 BC (Augustus) to 220 AD (Elegabalus) drank heavily.⁶ Claudius was reputedly a heavy drinker, and many features displayed by him and his relatives—bad temper, poor judgment, paranoia, impulsivity, violence, and sexual indiscretions—can result from alcohol abuse.

Psychosocial stressors. Claudius was raised and surrounded by malevolent people, then given almost limitless power. That mix of circumstances, plus fear fostered by persistent intrigue, may explain some of his behavior, particularly his brutality.

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The authors’ observations

Had laboratories been available in ancient Rome, a blood test would have determined whether Claudius suffered lead poisoning. Diagnosing bipolar disorder and/or alcoholism is much more difficult. Differentiating these disorders from each other and from other psychiatric disorders is challenging, as no laboratory tests confirm the diagnosis. Ongoing clinical observation of the illness and response to medication are crucial.

In some cases, having the patient list his or her depressive and manic episodes on a “life chart” might clarify the diagnosis. This exercise can also help the patient recognize bipolar symptoms and accept that he or she has the illness, which is critical to ensuring treatment adherence. Also start medication at this time.

Treatment

Treat bipolar disorder and alcoholism simultaneously, as either disorder could worsen the other’s course.^11,12

Lithium or valproate would be probable first-line treatments for Claudius. Discuss the medication’s risks and benefits with the patient and involved family members/caretakers. Inform them that you might have to change or add medication if the patient does not respond or experiences side effects.