Jeffrey Dunn, MD

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

Capgras’ causes. Capgras delusions can occur secondary to neurologic lesions and often appear to have an organic cause, such as abnormal focal paroxysmal discharges.¹ These delusions can occur secondary to systemic infections, thyroid dysfunction, seizures, concussion, intoxication dementia, toxic encephalopathy, or head trauma.^1,2 Theories vary as to physiologic, structural, and neurologic causes (Table).

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

Physiologic
Frontal lobe damage may distort visual stimuli monitoring, thus impairing facial recognition.4
Disruption of neuronal connections within the right temporal lobe scrambles memories needed for facial recognition.5
Neurologic
Disconnection between brain hemispheres lead to cognitive but not affective recognition.6
Bifrontal pathology or other organic cause blurs “judgment of individuality or uniqueness,” as in prosopagnosia.3
Dorsal pathway impairment alters affective response to faces.7
Dissociation in the amygdala may distort affective response to faces.8
Psychological*
In depression, misidentification develops secondary to rationalizing feelings of guilt and inferiority.9
“Two-armed recognition”—one automatic and almost instantaneous, the other attentive and mnemonic—begins to falter.10
Suspicion, preoccupation with details leads to “agnosia through too great attention.”11
Avoidance of unconscious desires leads to recognition problems.12
Patient “projects and splits” family member into two persons; directs love toward real person and hate toward imagined impostor.13
In schizophrenia, world is viewed through primitive mechanisms, such as doubles and dualism.14
*Dependent on psychiatric comorbidity

poll here

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.
  

Drug brand names

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

Disclosures

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

Capgras’ causes. Capgras delusions can occur secondary to neurologic lesions and often appear to have an organic cause, such as abnormal focal paroxysmal discharges.¹ These delusions can occur secondary to systemic infections, thyroid dysfunction, seizures, concussion, intoxication dementia, toxic encephalopathy, or head trauma.^1,2 Theories vary as to physiologic, structural, and neurologic causes (Table).

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

Physiologic
Frontal lobe damage may distort visual stimuli monitoring, thus impairing facial recognition.4
Disruption of neuronal connections within the right temporal lobe scrambles memories needed for facial recognition.5
Neurologic
Disconnection between brain hemispheres lead to cognitive but not affective recognition.6
Bifrontal pathology or other organic cause blurs “judgment of individuality or uniqueness,” as in prosopagnosia.3
Dorsal pathway impairment alters affective response to faces.7
Dissociation in the amygdala may distort affective response to faces.8
Psychological*
In depression, misidentification develops secondary to rationalizing feelings of guilt and inferiority.9
“Two-armed recognition”—one automatic and almost instantaneous, the other attentive and mnemonic—begins to falter.10
Suspicion, preoccupation with details leads to “agnosia through too great attention.”11
Avoidance of unconscious desires leads to recognition problems.12
Patient “projects and splits” family member into two persons; directs love toward real person and hate toward imagined impostor.13
In schizophrenia, world is viewed through primitive mechanisms, such as doubles and dualism.14
*Dependent on psychiatric comorbidity

poll here

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.
  

Drug brand names

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

Disclosures

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

Capgras’ causes. Capgras delusions can occur secondary to neurologic lesions and often appear to have an organic cause, such as abnormal focal paroxysmal discharges.¹ These delusions can occur secondary to systemic infections, thyroid dysfunction, seizures, concussion, intoxication dementia, toxic encephalopathy, or head trauma.^1,2 Theories vary as to physiologic, structural, and neurologic causes (Table).

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

Physiologic
Frontal lobe damage may distort visual stimuli monitoring, thus impairing facial recognition.4
Disruption of neuronal connections within the right temporal lobe scrambles memories needed for facial recognition.5
Neurologic
Disconnection between brain hemispheres lead to cognitive but not affective recognition.6
Bifrontal pathology or other organic cause blurs “judgment of individuality or uniqueness,” as in prosopagnosia.3
Dorsal pathway impairment alters affective response to faces.7
Dissociation in the amygdala may distort affective response to faces.8
Psychological*
In depression, misidentification develops secondary to rationalizing feelings of guilt and inferiority.9
“Two-armed recognition”—one automatic and almost instantaneous, the other attentive and mnemonic—begins to falter.10
Suspicion, preoccupation with details leads to “agnosia through too great attention.”11
Avoidance of unconscious desires leads to recognition problems.12
Patient “projects and splits” family member into two persons; directs love toward real person and hate toward imagined impostor.13
In schizophrenia, world is viewed through primitive mechanisms, such as doubles and dualism.14
*Dependent on psychiatric comorbidity

poll here

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.
  

Drug brand names

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

Disclosures

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

Emergency presentation: A rough commute

Mr. R, age 25, presented to the emergency room confused and severely agitated. That morning, his parents found him in his Philadelphia apartment covering his mouth and nose with a T-shirt to guard against imminent chemical warfare.

The day before, Mr. R had developed auditory and visual hallucinations and paranoid and persecutory delusions. That day, on his way to work, he said he had seen “terrorists releasing toxic chemicals into the air” and heard “whispers of terrorists plotting an attack on the East Coast.”

Mr. R showed no suicidal or homicidal ideations. He denied significant medical or surgical history but reported that he had recently been diagnosed with depression after a “bad Ecstasy experience.” For 6 months he had been taking paroxetine, 20 mg once daily, and bupropion, 150 mg once daily, for his depression.

At age 18, Mr. R was diagnosed with attention-deficit/hyperactivity disorder (ADHD) after years of struggling through school with impaired concentration. At that time, he began taking methylphenidate, 10 mg each morning, and completed 3 years of college in North Carolina. He then dropped out of college and attempted suicide twice.

After the second suicide attempt, a psychiatrist diagnosed Mr. R as having major depression. The psychiatrist discontinued methylphenidate and started bupropion, dosage unknown. After 1 year, he stopped taking the antidepressant, thinking he no longer needed it.

Last year, Mr. R moved back to Philadelphia to be closer to his parents. Shortly afterward, he began obtaining methylphenidate illegally and later starting using cocaine, marijuana, amphetamines, and 3,4-methylenedioxymethamphetamine (“Ecstasy”).

At presentation, Mr. R’s mood was dysphoric with bizarre affect. Eye contact was poor with easy distractibility. Speech was pressured, with full range. His thought process was grossly disorganized with tangential thinking and flight of ideas. His short- and long-term memory were intact; insight and judgment were limited. A Mini-Mental State Examination could not be completed because of his disorganization and distractibility.

Does Mr. R. have schizophrenia or schizoaffective disorder? Or are his symptoms related to ADHD or substance abuse?

The authors’ observations

Mr. R’s paranoid delusions and hallucinations may suggest schizophrenia. With his history of suicide attempts, a depressive or schizoaffective disorder may also be considered.

However, Mr. R is close with his family and has several friends. His parents say he has not been withdrawn or paranoid, and there is no known family history of mood disorder, substance abuse, or other psychiatric illness. Mr. R also has been working steadily and had worked the night before presenting to us, so schizophrenia and schizoaffective disorder are ruled out. ADHD and abuse of multiple substances could explain his behavior because overdose of stimulants and illicit drugs may produce a psychotic event.

Further history: The power of addiction

After more questioning, Mr. R said that he had recently started using gamma butyrolactone (GBL) in a failed attempt to build muscle. For 4 months he had been taking 3.5 oz of GBL daily—0.25 oz every 2 to 3 hours and 0.75 oz at night to help him sleep.

Within 6 hours of his most recent GBL dose (reportedly 1 oz), Mr. R developed intractable nausea, vomiting, and flatus, followed quickly by anxiety, palpitations, and generalized hand/body tremors that disturbed his sleep. Hallucinations and delusions started the next day.

At presentation, Mr. R’s blood pressure was 188/92 mm Hg, his heart rate was 110 bpm, and his respiratory rate was 22 breaths per minute. Pupils were 5 mm and reactive with intact extraocular movement. A urine drug screen indicated amphetamine use.

Mr. R was tentatively diagnosed as having GBL withdrawal syndrome and was admitted for observation and treatment. The psychiatry service followed him for change in mental status and drug dependence.

Can a withdrawal syndrome reasonably account for Mr. R’s symptoms?

The authors’ observations

GBL is a precursor of gamma-hydroxybutyrate (GHB), a highly addictive agent that is used illicitly, typically at parties and nightclubs (Box). GBL is among the clinical analogues of GHB that have become popular street drugs.

GHB withdrawal syndrome has only recently been described in the literature and is virtually indistinguishable from withdrawal after cessation of GBL and other precursors. To date, 71 deaths have been attributed to GHB withdrawal.²

A constellation of symptoms exhibited by Mr. R point to GHB withdrawal, which should be included in the differential diagnosis of any sedative/hypnotic withdrawal (Table 1).

How GHB works. GHB easily crosses the blood-brain barrier. Like other sedative/hypnotics, its depressant effects on the brain in low doses (2 to 4 grams) produce a euphoric feeling as inhibitions are depressed. Profound coma or death result from higher doses (>4 grams).³ Heart rate may also be slowed and CNS effects may result in myoclonus, producing seizure-like movements. Combining GHB with other drugs can increase the other agents’ depressant effects, leading to confusion, amnesia, vomiting, irregular breathing, or death.²

 

Box

A tiny increase in GHB dose can dramatically increase the symptoms and risk of overdose.⁴ GHB’s effects are also variable: A 1-teaspoon dose can produce the desired “high” one time and an overdose the next.

GHB and ethanol share a common mechanism of action.⁵ At pharmacologic doses, GHB appears to act in part through effects on the structurally related GABA neurotransmitter or its receptors.

Not surprisingly, a withdrawal syndrome characterized by delirium and autonomic instability ensues after GHB use is abruptly stopped. By functioning as indirect GABA agonists and ultimately evoking inhibitory neurotransmission, benzodiazepines and most barbiturates may alleviate GHB withdrawal symptoms.⁴ Thiamine is added to prevent Wernicke-Korsakoff syndrome, as is seen in alcohol withdrawal.⁵

GHB withdrawal. Symptoms are divided into three phases:

• Phase 1 (acute, first 24 hours). Presenting symptoms include anxiety, restlessness, insomnia, tremor, diaphoresis, tachycardia, and hypertension. Nausea and vomiting are variable but can be unrelenting.

While symptoms vary in severity, most prominent are agitation, restlessness, and insomnia. Some patients do not sleep for days after their last dose, and diffuse body tremors prevent them from sitting or lying still. Tachycardia and hypertension are hard to evaluate at this phase because patients present at different stages of withdrawal. Initial blood pressure readings as high as 240/130 mm Hg and heart rates of 120 bpm have been reported, however.

• Phase 2 (days 2 through 6). Worsening autonomic symptoms, progressive GI symptoms, and overall worsening of the withdrawal mark this tumultuous period. Patients usually present at this point—in acute distress and no longer able to self-treat.

Confusion, delirium, and florid psychosis characterize this phase. Mr. R’s paranoid delusions and hallucinations are the most common form of psychosis seen in GHB withdrawal.⁵ In some cases, the psychosis impairs social, occupational, and other functioning.

Table 1

Comparison of sedative-hypnotic withdrawal syndromes

Substance	Onset	Duration of severe symptoms	Autonomic instability*	Neurologic/psychiatric symptoms	Mortality	Major mechanism inducing withdrawal state‡
GHB	<6 hours	5 to 12 days	Mild	Severe	<1%	Loss of GHB, GABAA, and GABAB-mediated inhibition
Benzodiazepines	1 to 3 days	5 to 9 days	Moderate	Moderate	1%	Loss of GABAA-mediated inhibition
Baclofen	12 to 96 hours	8 days	Moderate	Severe	None reported	Loss of GABAB-mediated inhibition
Ethanol	<6 hours	10 to 14 days	Severe	Moderate to severe	5% to 15%	Loss of GABAA-mediated inhibition; disinhibition of NMDA receptors
NMDA: N-methyl D-aspartate.
GHB: Gamma-hydroxybutyrate
*Marked by tachycardia, fever, hypertension, and/or diaphoresis.
‡All withdrawal states involve multifactorial processes.
Source: Reference 5

Underlying or concurrent causes of delirium must be ruled out. Patients at this stage often require physical restraint or immediate sedation to prevent injury and dangerous complications, including hyperthermia and rhabdomyolysis. Benzodiazepines are often used in high doses¹ for sedation. IV hydration and antiemetics are also treatment mainstays. Atypical antipsychotics are added ASAP to control the paranoia.

• Phase 3 (days 7 through 13). Symptoms usually resolve at this stage. The delirium most often clears first, followed by restored autonomic stability and GI rest. While decreased sleep and periods of psychosis persist, agitation is less severe. The patient is discharged on average after 11 days.

Intense outpatient follow-up should include individual psychotherapy, substance abuse counseling, and drug therapy. Highly addictive medications should be avoided because of the patient’s substance abuse history.

Did Mr. R accurately report the amount of GBL he had taken? How should GBL and GHB blood levels be measured, given the agents’ rapid absorption rates?

The authors’ observations

As with most drugs of abuse, high doses over time contribute to severe GHB withdrawal syndrome. GHB doses taken before withdrawal are up to 10 times greater than those taken in typical recreational use.⁵

However, quantifying GHB levels with standard urine drug screens is nearly impossible because:

 

• the agent is absorbed within 20 to 60 minutes
• only 2% to 5% of the agent is eliminated in the urine.

GHB—which comes in powder, tablet, and liquid form and is usually dissolved in water before use—often is mixed with other drugs or alcohol. Varying preparations and use with multiple substances can produce inconsistent GHB levels and decrease sensitivity and specificity in routine drug screening. GHB abusers also report the amount ingested in “capfuls,” ounces, and teaspoons, making accurate quantification harder still.²

Though infrequently used because of feasibility and cost, gas chromatography and infrared spectroscopy of a urine specimen are the only known methods for determining GHB levels. Chronic GHB use, negative polypharmacy history, and negative urine and blood analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances usually confirm GHB withdrawal diagnosis.¹

Treatment: ‘Bad’ medicine

In the ER, Mr. R was given two 1-mg doses of lorazepam IV 1 hour apart. After 1 hour, his vital signs improved slightly (heart rate: 100/min; blood pressure: 165/99 mm Hg). Thiamine and folate were also started. Mr. R’s severe agitation and paranoia persisted, so three more 2-mg doses of lorazepam IV were given at 4-hour intervals.

Within 2 days, Mr. R was transferred to the voluntary inpatient psychiatric unit. His nausea, vomiting, and autonomic instability resolved, but his delirium and psychosis persisted. Quetiapine, 100 mg bid, was started to address his psychosis, and bupropion, 150 mg once daily, was restarted to manage his previously diagnosed depression. Three days after starting bupropion, Mr. R’s mood improved based on patient reports and Clinical Global Impression scores (6 at baseline, 2 at discharge), but his persecutory delusions persisted, causing mild anxiety.

The next day, Mr. R’s auditory and visual hallucinations had ceased, his preoccupation with terrorists began to subside, and his concentration, sleep, and appetite were improving. By day 6 of hospitalization, he still complained of mild tremors and anxiety, but his persecutory delusions resolved.

After 9 days, Mr. R was discharged. Autonomic stability was achieved and his delirium had mostly resolved. Outpatient drug rehabilitation and psychiatric services were arranged.

As of this writing, Mr. R had not sought outpatient treatment. His current medical status is unknown.

Related resources

• Miglani J, Kim K, Chahil R. Gamma-hydroxybutyrate withdrawal delirium: a case report. Gen Hosp Psychiatry. 2000;22:213-6.
• Columbo G, Agabio R, Lobina C, et al. Cross tolerance to ethanol and gamma-hydroxybutyric acid. Eur J Pharmacol. 1995;273:235-8.
• Project GHB. www.projectghb.org

Drug brand names

• Bupropion • Wellbutrin
• Lorazepam • Ativan
• Methylphenidate • Ritalin, Concerta
• Paroxetine • Paxil
• Quetiapine • Seroquel

Disclosure

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

Emergency presentation: A rough commute

Mr. R, age 25, presented to the emergency room confused and severely agitated. That morning, his parents found him in his Philadelphia apartment covering his mouth and nose with a T-shirt to guard against imminent chemical warfare.

The day before, Mr. R had developed auditory and visual hallucinations and paranoid and persecutory delusions. That day, on his way to work, he said he had seen “terrorists releasing toxic chemicals into the air” and heard “whispers of terrorists plotting an attack on the East Coast.”

Mr. R showed no suicidal or homicidal ideations. He denied significant medical or surgical history but reported that he had recently been diagnosed with depression after a “bad Ecstasy experience.” For 6 months he had been taking paroxetine, 20 mg once daily, and bupropion, 150 mg once daily, for his depression.

At age 18, Mr. R was diagnosed with attention-deficit/hyperactivity disorder (ADHD) after years of struggling through school with impaired concentration. At that time, he began taking methylphenidate, 10 mg each morning, and completed 3 years of college in North Carolina. He then dropped out of college and attempted suicide twice.

After the second suicide attempt, a psychiatrist diagnosed Mr. R as having major depression. The psychiatrist discontinued methylphenidate and started bupropion, dosage unknown. After 1 year, he stopped taking the antidepressant, thinking he no longer needed it.

Last year, Mr. R moved back to Philadelphia to be closer to his parents. Shortly afterward, he began obtaining methylphenidate illegally and later starting using cocaine, marijuana, amphetamines, and 3,4-methylenedioxymethamphetamine (“Ecstasy”).

At presentation, Mr. R’s mood was dysphoric with bizarre affect. Eye contact was poor with easy distractibility. Speech was pressured, with full range. His thought process was grossly disorganized with tangential thinking and flight of ideas. His short- and long-term memory were intact; insight and judgment were limited. A Mini-Mental State Examination could not be completed because of his disorganization and distractibility.

Does Mr. R. have schizophrenia or schizoaffective disorder? Or are his symptoms related to ADHD or substance abuse?

The authors’ observations

Mr. R’s paranoid delusions and hallucinations may suggest schizophrenia. With his history of suicide attempts, a depressive or schizoaffective disorder may also be considered.

However, Mr. R is close with his family and has several friends. His parents say he has not been withdrawn or paranoid, and there is no known family history of mood disorder, substance abuse, or other psychiatric illness. Mr. R also has been working steadily and had worked the night before presenting to us, so schizophrenia and schizoaffective disorder are ruled out. ADHD and abuse of multiple substances could explain his behavior because overdose of stimulants and illicit drugs may produce a psychotic event.

Further history: The power of addiction

After more questioning, Mr. R said that he had recently started using gamma butyrolactone (GBL) in a failed attempt to build muscle. For 4 months he had been taking 3.5 oz of GBL daily—0.25 oz every 2 to 3 hours and 0.75 oz at night to help him sleep.

Within 6 hours of his most recent GBL dose (reportedly 1 oz), Mr. R developed intractable nausea, vomiting, and flatus, followed quickly by anxiety, palpitations, and generalized hand/body tremors that disturbed his sleep. Hallucinations and delusions started the next day.

At presentation, Mr. R’s blood pressure was 188/92 mm Hg, his heart rate was 110 bpm, and his respiratory rate was 22 breaths per minute. Pupils were 5 mm and reactive with intact extraocular movement. A urine drug screen indicated amphetamine use.

Mr. R was tentatively diagnosed as having GBL withdrawal syndrome and was admitted for observation and treatment. The psychiatry service followed him for change in mental status and drug dependence.

Can a withdrawal syndrome reasonably account for Mr. R’s symptoms?

The authors’ observations

GBL is a precursor of gamma-hydroxybutyrate (GHB), a highly addictive agent that is used illicitly, typically at parties and nightclubs (Box). GBL is among the clinical analogues of GHB that have become popular street drugs.

GHB withdrawal syndrome has only recently been described in the literature and is virtually indistinguishable from withdrawal after cessation of GBL and other precursors. To date, 71 deaths have been attributed to GHB withdrawal.²

A constellation of symptoms exhibited by Mr. R point to GHB withdrawal, which should be included in the differential diagnosis of any sedative/hypnotic withdrawal (Table 1).

How GHB works. GHB easily crosses the blood-brain barrier. Like other sedative/hypnotics, its depressant effects on the brain in low doses (2 to 4 grams) produce a euphoric feeling as inhibitions are depressed. Profound coma or death result from higher doses (>4 grams).³ Heart rate may also be slowed and CNS effects may result in myoclonus, producing seizure-like movements. Combining GHB with other drugs can increase the other agents’ depressant effects, leading to confusion, amnesia, vomiting, irregular breathing, or death.²

 

Box

A tiny increase in GHB dose can dramatically increase the symptoms and risk of overdose.⁴ GHB’s effects are also variable: A 1-teaspoon dose can produce the desired “high” one time and an overdose the next.

GHB and ethanol share a common mechanism of action.⁵ At pharmacologic doses, GHB appears to act in part through effects on the structurally related GABA neurotransmitter or its receptors.

Not surprisingly, a withdrawal syndrome characterized by delirium and autonomic instability ensues after GHB use is abruptly stopped. By functioning as indirect GABA agonists and ultimately evoking inhibitory neurotransmission, benzodiazepines and most barbiturates may alleviate GHB withdrawal symptoms.⁴ Thiamine is added to prevent Wernicke-Korsakoff syndrome, as is seen in alcohol withdrawal.⁵

GHB withdrawal. Symptoms are divided into three phases:

• Phase 1 (acute, first 24 hours). Presenting symptoms include anxiety, restlessness, insomnia, tremor, diaphoresis, tachycardia, and hypertension. Nausea and vomiting are variable but can be unrelenting.

While symptoms vary in severity, most prominent are agitation, restlessness, and insomnia. Some patients do not sleep for days after their last dose, and diffuse body tremors prevent them from sitting or lying still. Tachycardia and hypertension are hard to evaluate at this phase because patients present at different stages of withdrawal. Initial blood pressure readings as high as 240/130 mm Hg and heart rates of 120 bpm have been reported, however.

• Phase 2 (days 2 through 6). Worsening autonomic symptoms, progressive GI symptoms, and overall worsening of the withdrawal mark this tumultuous period. Patients usually present at this point—in acute distress and no longer able to self-treat.

Confusion, delirium, and florid psychosis characterize this phase. Mr. R’s paranoid delusions and hallucinations are the most common form of psychosis seen in GHB withdrawal.⁵ In some cases, the psychosis impairs social, occupational, and other functioning.

Table 1

Comparison of sedative-hypnotic withdrawal syndromes

Substance	Onset	Duration of severe symptoms	Autonomic instability*	Neurologic/psychiatric symptoms	Mortality	Major mechanism inducing withdrawal state‡
GHB	<6 hours	5 to 12 days	Mild	Severe	<1%	Loss of GHB, GABAA, and GABAB-mediated inhibition
Benzodiazepines	1 to 3 days	5 to 9 days	Moderate	Moderate	1%	Loss of GABAA-mediated inhibition
Baclofen	12 to 96 hours	8 days	Moderate	Severe	None reported	Loss of GABAB-mediated inhibition
Ethanol	<6 hours	10 to 14 days	Severe	Moderate to severe	5% to 15%	Loss of GABAA-mediated inhibition; disinhibition of NMDA receptors
NMDA: N-methyl D-aspartate.
GHB: Gamma-hydroxybutyrate
*Marked by tachycardia, fever, hypertension, and/or diaphoresis.
‡All withdrawal states involve multifactorial processes.
Source: Reference 5

Underlying or concurrent causes of delirium must be ruled out. Patients at this stage often require physical restraint or immediate sedation to prevent injury and dangerous complications, including hyperthermia and rhabdomyolysis. Benzodiazepines are often used in high doses¹ for sedation. IV hydration and antiemetics are also treatment mainstays. Atypical antipsychotics are added ASAP to control the paranoia.

• Phase 3 (days 7 through 13). Symptoms usually resolve at this stage. The delirium most often clears first, followed by restored autonomic stability and GI rest. While decreased sleep and periods of psychosis persist, agitation is less severe. The patient is discharged on average after 11 days.

Intense outpatient follow-up should include individual psychotherapy, substance abuse counseling, and drug therapy. Highly addictive medications should be avoided because of the patient’s substance abuse history.

Did Mr. R accurately report the amount of GBL he had taken? How should GBL and GHB blood levels be measured, given the agents’ rapid absorption rates?

The authors’ observations

As with most drugs of abuse, high doses over time contribute to severe GHB withdrawal syndrome. GHB doses taken before withdrawal are up to 10 times greater than those taken in typical recreational use.⁵

However, quantifying GHB levels with standard urine drug screens is nearly impossible because:

 

• the agent is absorbed within 20 to 60 minutes
• only 2% to 5% of the agent is eliminated in the urine.

GHB—which comes in powder, tablet, and liquid form and is usually dissolved in water before use—often is mixed with other drugs or alcohol. Varying preparations and use with multiple substances can produce inconsistent GHB levels and decrease sensitivity and specificity in routine drug screening. GHB abusers also report the amount ingested in “capfuls,” ounces, and teaspoons, making accurate quantification harder still.²

Though infrequently used because of feasibility and cost, gas chromatography and infrared spectroscopy of a urine specimen are the only known methods for determining GHB levels. Chronic GHB use, negative polypharmacy history, and negative urine and blood analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances usually confirm GHB withdrawal diagnosis.¹

Treatment: ‘Bad’ medicine

In the ER, Mr. R was given two 1-mg doses of lorazepam IV 1 hour apart. After 1 hour, his vital signs improved slightly (heart rate: 100/min; blood pressure: 165/99 mm Hg). Thiamine and folate were also started. Mr. R’s severe agitation and paranoia persisted, so three more 2-mg doses of lorazepam IV were given at 4-hour intervals.

Within 2 days, Mr. R was transferred to the voluntary inpatient psychiatric unit. His nausea, vomiting, and autonomic instability resolved, but his delirium and psychosis persisted. Quetiapine, 100 mg bid, was started to address his psychosis, and bupropion, 150 mg once daily, was restarted to manage his previously diagnosed depression. Three days after starting bupropion, Mr. R’s mood improved based on patient reports and Clinical Global Impression scores (6 at baseline, 2 at discharge), but his persecutory delusions persisted, causing mild anxiety.

The next day, Mr. R’s auditory and visual hallucinations had ceased, his preoccupation with terrorists began to subside, and his concentration, sleep, and appetite were improving. By day 6 of hospitalization, he still complained of mild tremors and anxiety, but his persecutory delusions resolved.

After 9 days, Mr. R was discharged. Autonomic stability was achieved and his delirium had mostly resolved. Outpatient drug rehabilitation and psychiatric services were arranged.

As of this writing, Mr. R had not sought outpatient treatment. His current medical status is unknown.

Related resources

• Miglani J, Kim K, Chahil R. Gamma-hydroxybutyrate withdrawal delirium: a case report. Gen Hosp Psychiatry. 2000;22:213-6.
• Columbo G, Agabio R, Lobina C, et al. Cross tolerance to ethanol and gamma-hydroxybutyric acid. Eur J Pharmacol. 1995;273:235-8.
• Project GHB. www.projectghb.org

Drug brand names

• Bupropion • Wellbutrin
• Lorazepam • Ativan
• Methylphenidate • Ritalin, Concerta
• Paroxetine • Paxil
• Quetiapine • Seroquel

Disclosure

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

Emergency presentation: A rough commute

Mr. R, age 25, presented to the emergency room confused and severely agitated. That morning, his parents found him in his Philadelphia apartment covering his mouth and nose with a T-shirt to guard against imminent chemical warfare.

The day before, Mr. R had developed auditory and visual hallucinations and paranoid and persecutory delusions. That day, on his way to work, he said he had seen “terrorists releasing toxic chemicals into the air” and heard “whispers of terrorists plotting an attack on the East Coast.”

Mr. R showed no suicidal or homicidal ideations. He denied significant medical or surgical history but reported that he had recently been diagnosed with depression after a “bad Ecstasy experience.” For 6 months he had been taking paroxetine, 20 mg once daily, and bupropion, 150 mg once daily, for his depression.

At age 18, Mr. R was diagnosed with attention-deficit/hyperactivity disorder (ADHD) after years of struggling through school with impaired concentration. At that time, he began taking methylphenidate, 10 mg each morning, and completed 3 years of college in North Carolina. He then dropped out of college and attempted suicide twice.

After the second suicide attempt, a psychiatrist diagnosed Mr. R as having major depression. The psychiatrist discontinued methylphenidate and started bupropion, dosage unknown. After 1 year, he stopped taking the antidepressant, thinking he no longer needed it.

Last year, Mr. R moved back to Philadelphia to be closer to his parents. Shortly afterward, he began obtaining methylphenidate illegally and later starting using cocaine, marijuana, amphetamines, and 3,4-methylenedioxymethamphetamine (“Ecstasy”).

At presentation, Mr. R’s mood was dysphoric with bizarre affect. Eye contact was poor with easy distractibility. Speech was pressured, with full range. His thought process was grossly disorganized with tangential thinking and flight of ideas. His short- and long-term memory were intact; insight and judgment were limited. A Mini-Mental State Examination could not be completed because of his disorganization and distractibility.

Does Mr. R. have schizophrenia or schizoaffective disorder? Or are his symptoms related to ADHD or substance abuse?

The authors’ observations

Mr. R’s paranoid delusions and hallucinations may suggest schizophrenia. With his history of suicide attempts, a depressive or schizoaffective disorder may also be considered.

However, Mr. R is close with his family and has several friends. His parents say he has not been withdrawn or paranoid, and there is no known family history of mood disorder, substance abuse, or other psychiatric illness. Mr. R also has been working steadily and had worked the night before presenting to us, so schizophrenia and schizoaffective disorder are ruled out. ADHD and abuse of multiple substances could explain his behavior because overdose of stimulants and illicit drugs may produce a psychotic event.

Further history: The power of addiction

After more questioning, Mr. R said that he had recently started using gamma butyrolactone (GBL) in a failed attempt to build muscle. For 4 months he had been taking 3.5 oz of GBL daily—0.25 oz every 2 to 3 hours and 0.75 oz at night to help him sleep.

Within 6 hours of his most recent GBL dose (reportedly 1 oz), Mr. R developed intractable nausea, vomiting, and flatus, followed quickly by anxiety, palpitations, and generalized hand/body tremors that disturbed his sleep. Hallucinations and delusions started the next day.

At presentation, Mr. R’s blood pressure was 188/92 mm Hg, his heart rate was 110 bpm, and his respiratory rate was 22 breaths per minute. Pupils were 5 mm and reactive with intact extraocular movement. A urine drug screen indicated amphetamine use.

Mr. R was tentatively diagnosed as having GBL withdrawal syndrome and was admitted for observation and treatment. The psychiatry service followed him for change in mental status and drug dependence.

Can a withdrawal syndrome reasonably account for Mr. R’s symptoms?

The authors’ observations

GBL is a precursor of gamma-hydroxybutyrate (GHB), a highly addictive agent that is used illicitly, typically at parties and nightclubs (Box). GBL is among the clinical analogues of GHB that have become popular street drugs.

GHB withdrawal syndrome has only recently been described in the literature and is virtually indistinguishable from withdrawal after cessation of GBL and other precursors. To date, 71 deaths have been attributed to GHB withdrawal.²

A constellation of symptoms exhibited by Mr. R point to GHB withdrawal, which should be included in the differential diagnosis of any sedative/hypnotic withdrawal (Table 1).

How GHB works. GHB easily crosses the blood-brain barrier. Like other sedative/hypnotics, its depressant effects on the brain in low doses (2 to 4 grams) produce a euphoric feeling as inhibitions are depressed. Profound coma or death result from higher doses (>4 grams).³ Heart rate may also be slowed and CNS effects may result in myoclonus, producing seizure-like movements. Combining GHB with other drugs can increase the other agents’ depressant effects, leading to confusion, amnesia, vomiting, irregular breathing, or death.²

 

Box

A tiny increase in GHB dose can dramatically increase the symptoms and risk of overdose.⁴ GHB’s effects are also variable: A 1-teaspoon dose can produce the desired “high” one time and an overdose the next.

GHB and ethanol share a common mechanism of action.⁵ At pharmacologic doses, GHB appears to act in part through effects on the structurally related GABA neurotransmitter or its receptors.

Not surprisingly, a withdrawal syndrome characterized by delirium and autonomic instability ensues after GHB use is abruptly stopped. By functioning as indirect GABA agonists and ultimately evoking inhibitory neurotransmission, benzodiazepines and most barbiturates may alleviate GHB withdrawal symptoms.⁴ Thiamine is added to prevent Wernicke-Korsakoff syndrome, as is seen in alcohol withdrawal.⁵

GHB withdrawal. Symptoms are divided into three phases:

• Phase 1 (acute, first 24 hours). Presenting symptoms include anxiety, restlessness, insomnia, tremor, diaphoresis, tachycardia, and hypertension. Nausea and vomiting are variable but can be unrelenting.

While symptoms vary in severity, most prominent are agitation, restlessness, and insomnia. Some patients do not sleep for days after their last dose, and diffuse body tremors prevent them from sitting or lying still. Tachycardia and hypertension are hard to evaluate at this phase because patients present at different stages of withdrawal. Initial blood pressure readings as high as 240/130 mm Hg and heart rates of 120 bpm have been reported, however.

• Phase 2 (days 2 through 6). Worsening autonomic symptoms, progressive GI symptoms, and overall worsening of the withdrawal mark this tumultuous period. Patients usually present at this point—in acute distress and no longer able to self-treat.

Confusion, delirium, and florid psychosis characterize this phase. Mr. R’s paranoid delusions and hallucinations are the most common form of psychosis seen in GHB withdrawal.⁵ In some cases, the psychosis impairs social, occupational, and other functioning.

Table 1

Comparison of sedative-hypnotic withdrawal syndromes

Substance	Onset	Duration of severe symptoms	Autonomic instability*	Neurologic/psychiatric symptoms	Mortality	Major mechanism inducing withdrawal state‡
GHB	<6 hours	5 to 12 days	Mild	Severe	<1%	Loss of GHB, GABAA, and GABAB-mediated inhibition
Benzodiazepines	1 to 3 days	5 to 9 days	Moderate	Moderate	1%	Loss of GABAA-mediated inhibition
Baclofen	12 to 96 hours	8 days	Moderate	Severe	None reported	Loss of GABAB-mediated inhibition
Ethanol	<6 hours	10 to 14 days	Severe	Moderate to severe	5% to 15%	Loss of GABAA-mediated inhibition; disinhibition of NMDA receptors
NMDA: N-methyl D-aspartate.
GHB: Gamma-hydroxybutyrate
*Marked by tachycardia, fever, hypertension, and/or diaphoresis.
‡All withdrawal states involve multifactorial processes.
Source: Reference 5

Underlying or concurrent causes of delirium must be ruled out. Patients at this stage often require physical restraint or immediate sedation to prevent injury and dangerous complications, including hyperthermia and rhabdomyolysis. Benzodiazepines are often used in high doses¹ for sedation. IV hydration and antiemetics are also treatment mainstays. Atypical antipsychotics are added ASAP to control the paranoia.

• Phase 3 (days 7 through 13). Symptoms usually resolve at this stage. The delirium most often clears first, followed by restored autonomic stability and GI rest. While decreased sleep and periods of psychosis persist, agitation is less severe. The patient is discharged on average after 11 days.

Intense outpatient follow-up should include individual psychotherapy, substance abuse counseling, and drug therapy. Highly addictive medications should be avoided because of the patient’s substance abuse history.

Did Mr. R accurately report the amount of GBL he had taken? How should GBL and GHB blood levels be measured, given the agents’ rapid absorption rates?

The authors’ observations

As with most drugs of abuse, high doses over time contribute to severe GHB withdrawal syndrome. GHB doses taken before withdrawal are up to 10 times greater than those taken in typical recreational use.⁵

However, quantifying GHB levels with standard urine drug screens is nearly impossible because:

 

• the agent is absorbed within 20 to 60 minutes
• only 2% to 5% of the agent is eliminated in the urine.

GHB—which comes in powder, tablet, and liquid form and is usually dissolved in water before use—often is mixed with other drugs or alcohol. Varying preparations and use with multiple substances can produce inconsistent GHB levels and decrease sensitivity and specificity in routine drug screening. GHB abusers also report the amount ingested in “capfuls,” ounces, and teaspoons, making accurate quantification harder still.²

Though infrequently used because of feasibility and cost, gas chromatography and infrared spectroscopy of a urine specimen are the only known methods for determining GHB levels. Chronic GHB use, negative polypharmacy history, and negative urine and blood analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances usually confirm GHB withdrawal diagnosis.¹

Treatment: ‘Bad’ medicine

In the ER, Mr. R was given two 1-mg doses of lorazepam IV 1 hour apart. After 1 hour, his vital signs improved slightly (heart rate: 100/min; blood pressure: 165/99 mm Hg). Thiamine and folate were also started. Mr. R’s severe agitation and paranoia persisted, so three more 2-mg doses of lorazepam IV were given at 4-hour intervals.

Within 2 days, Mr. R was transferred to the voluntary inpatient psychiatric unit. His nausea, vomiting, and autonomic instability resolved, but his delirium and psychosis persisted. Quetiapine, 100 mg bid, was started to address his psychosis, and bupropion, 150 mg once daily, was restarted to manage his previously diagnosed depression. Three days after starting bupropion, Mr. R’s mood improved based on patient reports and Clinical Global Impression scores (6 at baseline, 2 at discharge), but his persecutory delusions persisted, causing mild anxiety.

The next day, Mr. R’s auditory and visual hallucinations had ceased, his preoccupation with terrorists began to subside, and his concentration, sleep, and appetite were improving. By day 6 of hospitalization, he still complained of mild tremors and anxiety, but his persecutory delusions resolved.

After 9 days, Mr. R was discharged. Autonomic stability was achieved and his delirium had mostly resolved. Outpatient drug rehabilitation and psychiatric services were arranged.

As of this writing, Mr. R had not sought outpatient treatment. His current medical status is unknown.

Related resources

• Miglani J, Kim K, Chahil R. Gamma-hydroxybutyrate withdrawal delirium: a case report. Gen Hosp Psychiatry. 2000;22:213-6.
• Columbo G, Agabio R, Lobina C, et al. Cross tolerance to ethanol and gamma-hydroxybutyric acid. Eur J Pharmacol. 1995;273:235-8.
• Project GHB. www.projectghb.org

Drug brand names

• Bupropion • Wellbutrin
• Lorazepam • Ativan
• Methylphenidate • Ritalin, Concerta
• Paroxetine • Paxil
• Quetiapine • Seroquel

Disclosure

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