Cases That Test Your Skills

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CASE: Gl surgery

Ms. X, age 61, presents to the emergency department (ED) complaining of nausea, vomiting, and abdominal pain and distension. CT scan of her abdomen reveals segmental ischemia in her colon with abscess formation, which leads to immediate surgery, including ileocecostomy with primary anastomosis. After surgery, Ms. X suffers from gastrointestinal (GI) dysmotility. The gastroenterology team recommends daily enemas along with a soft diet after she is discharged.

Ms. X has chronic paranoid schizophrenia, which has been treated successfully for 18 years with clozapine, 500 mg/d. During acute psychotic episodes, she experienced paranoid delusions and command auditory hallucinations telling her to kill herself. She had previous trials of several antipsychotics, including quetiapine, thiothixene, thioridazine, trifluoperazine, chlorpromazine, and haloperidol, all of which were ineffective and poorly tolerated because of serious side effects.

Within 1 month of discharge, Ms. X returns to the ED with nausea, vomiting, and abdominal distension. Abdominal CT scan suggests partial small bowel obstruction and significantly dilated loops of small bowel with decompressed rectum and sigmoid colon. Considering her recent GI surgery and absence of abdominal pain, she is managed with conservative measures, including nasogastric tube decompression and total parenteral nutrition. CT enterography demonstrates no areas of stricture formation with interval decompression.

The psychiatric service is consulted to evaluate the possibility of clozapine-induced paralytic ileus. During initial assessment, Ms. X denies any psychotic symptoms, including paranoid ideations, delusions, and auditory or visual hallucinations, and firmly believes that clozapine helps keep her stable. She also denies mood symptoms that could indicate mania or depression. She shows no signs or symptoms that suggest anticholinergic delirium.

The authors’ observations

Clozapine has proven efficacy in managing treatment-resistant schizophrenia,^1-3 but the drug has been associated with life-threatening side effects, including agranulocytosis/neutropenia, myocarditis/cardiomyopathy, arrhythmia, seizures, diabetic ketoacidosis, fulminant hepatic failure, pulmonary embolism, and GI complications.⁴

Clozapine-induced GI side effects include anorexia, nausea, vomiting, heartburn, abdominal discomfort, diarrhea, and constipation. Clozapine-induced gastrointestinal hypomotility (CIGH) can lead to fecalith formation, which may result in intestinal obstruction/pseudo-obstruction, intestinal distension, necrosis, perforation, sepsis, aspiration from inhalation of feculent vomitus, or dysphagia.⁵ Constipation has been reported in 14% to 60% of patients who take clozapine,⁶ although other psychiatric medications also can cause constipation (Table 1). Severe constipation can lead to potentially fatal GI complications such as intestinal obstruction, necrosis, perforation, and sepsis, which is associated with significant morbidity due to bowel resection and a 27.5% mortality rate.⁵

The underlying mechanism of clozapine-induced constipation has been well established. The gut is innervated mainly by cholinergic and serotonergic receptors (5-HT3) and these receptors are responsible for peristalsis. Clozapine has a potent anticholinergic effect and acts as a strong antagonist of serotonin receptors (5-HT2, 5-HT3, 5-HT6, 5-HT7), which can lead to gut hypomotility.⁷ Risk factors associated with CIGH include:

• high dose of clozapine (mean dosage >428 mg/d)
• high serum clozapine levels (>500 ng/mL)
• coadministration of anticholinergic medications
• concomitant use of cytochrome P450 (CYP) enzyme inhibitors (medications inhibiting CYP1A2 enzyme)
• comorbid medical illnesses
• fever
• history of surgical bowel resection, GI pathology, and constipation.⁵

Table 1

Psychotropics associated with constipation

HISTORY: Medical comorbidities

Ms. X’s medical history is significant for chronic constipation, hypertension, obstructive pulmonary disease, and hyperthyroidism. Her medications include trazodone, 25 mg/d; fluoxetine, 40 mg/d, for negative symptoms and insomnia; docusate sodium, 200 mg/d; polyethylene glycol, 17 g/d; and bisacodyl suppository, 10 mg as needed for constipation. On admission, her laboratory test results—including complete blood count, liver function tests, kidney function tests, thyroid function profile, and serum calcium levels—all were within normal range.

The authors’ observations

Because the prevalence and severity of clozapine-induced constipation seem to be dose-dependent,⁸ minimizing the dosage is a logical management strategy.⁹ The life-threatening nature of clozapine-induced GI complications may require rapid dose reduction, which could compromise a patient’s stability. There is a little evidence regarding systematic management of clozapine-induced GI complications (Table 2).

Table 2

Clinical pearls for treating clozapine-induced constipation

TREATMENT: Clozapine reduction

We obtain a serum clozapine level, which is elevated at 553 ng/mL. We recommend gradual reducing Ms. X’s clozapine dosage by 50 mg every 3 to 4 days to reach a target dose of 300 to 350 mg/d, to attain serum clozapine levels 350 to 400 ng/mL. Because of trazodone’s potential anticholinergic action, which could be worsening Ms. X’s constipation, we stop the drug and begin zolpidem, 5 to 10 mg/d, to manage her insomnia. During these medication changes, we closely monitor Ms. X for reemerging psychotic symptoms.

The authors’ observations

In addition to risk factors such as chronic constipation and recent GI surgery, Ms. X’s supra-therapeutic serum clozapine level (553 ng/mL) significantly increased her risk of clozapine-induced paralytic ileus. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are known to increase tissue concentrations of clozapine and its major metabolite, norclozapine, by primarily inhibiting CYP1A2 and perhaps CYP2D6.¹⁰ As a potent inhibitor of CYPA12, fluvoxamine can inhibit clozapine metabolism, resulting in higher plasma concentrations.¹¹ In Ms. X’s case, fluoxetine could have increased serum clozapine levels because of its ability to inhibit clozapine metabolism via CYP2D6-mediated mechanisms.¹²

Although clozapine serum levels are not routinely measured, such testing may be indicated in patients who do not respond to or are unable to tolerate clozapine. Clozapine levels should be obtained 12 hours after the bedtime dose (trough levels), several days after clozapine initiation. Serum clozapine levels <350 ng/mL are associated with lack of clinical response.¹³ Higher serum levels (500 to 700 ng/mL) have been associated with greater incidences of serious GI complications. Serum clozapine levels also help guide clozapine dosage reduction because of its linear kinetics—halving the dose will halve the serum clozapine level.¹⁴

OUTCOME: GI symptoms improve

Ms. X shows improved GI motility within few days of the first decrease in her clozapine dosage. Nausea, vomiting, and abdominal distension gradually resolve over 2 weeks with concomitant reduction in clozapine dosage to 300 mg/d (50 mg in the morning and 250 mg at bedtime) without reemergence of psychotic symptoms. She is able to tolerate a soft diet, and conservative GI measures are no longer required. She is discharged home with outpatient surgical and psychiatric follow-up.

The authors’ observations

Successful reversal of severe clozapine-induced constipation—occurring at serum clozapine level of 490 ng/mL—has been reported in a 45-year-old man with treatment-resistant schizophrenia. This was accomplished by cautious reduction of clozapine dosage (400 mg/d to 250 mg/d) over 1 week.¹⁵ Slower clozapine titration—reducing the dose by no more than 25 mg/d to a maximum of 100 mg/week—has been recommended.¹⁶ It also has been suggested to replace part of the clozapine dose with a less antimuscarinic antipsychotic, such as quetiapine or haloperidol, thereby using the second antipsychotic as a clozapine-sparing agent.⁹ For example, the clozapine dose could be reduced by 25% by substituting 2 mg of quetiapine for every 1 mg of clozapine.

Prevention

Psychiatrists who prescribe clozapine should take a careful history of risk factors that might predispose patients to clozapine-induced GI side effects. Caution patients to whom you prescribe clozapine about possible development of constipation and the risk of serious GI complications. Enlist family members and caseworkers to keep a close eye on GI side effects in patients receiving clozapine. Advise patients to prevent constipation by eating a high fiber diet, drinking adequate fluids, and getting regular exercise. Patients should be treated aggressively with laxatives to relieve constipation and educated about the warning signs of intestinal obstruction, such as worsening constipation, abdominal pain, vomiting, and inability to pass flatus.¹⁷

Rapidly fatal bowel ischemia caused by clozapine has been reported.¹⁸ Therefore, urgently refer patients for medical evaluation if you have any concerns about worsening constipation or observe signs of intestinal obstruction. Vigilant consideration of clozapine as a likely culprit in severe GI complications in inpatient settings can prevent morbidity and mortality.

In our case, cautious reduction of clozapine dosage, guided by serum clozapine levels, had obviated the need for surgery and prevented reemergence of psychotic symptoms.

Related Resources

• Drew L, Herdson P. Clozapine and constipation: a serious issue. Aust N Z J Psychiatry. 1997;31(1):149-150.
• Winstead NS, Winstead DK. 5-step plan to treat constipation in psychiatric patients. Current Psychiatry. 2008;7(5):29-39.

Drug Brand Names

• Amitriptyline • Elavil
• Benztropine • Cogentin
• Bisacodyl suppository • Dulcolax, others
• Chlorpromazine • Thorazine
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Docusate sodium • Colace, others
• Doxepin • Adapin, Sinequan
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Nortriptyline • Aventyl, Pamelor
• Pimozide • Orap
• Polyethylene glycol • MiraLax
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel, Oleptro
• Trifluoperazine • Stelazine
• Trihexyphenidyl • Artane, Trihexane
• Trimipramine • Surmontil
• Zolpidem • Ambien

Disclosure

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

Discuss this article at www.facebook.com/CurrentPsychiatry

CASE: Gl surgery

Ms. X, age 61, presents to the emergency department (ED) complaining of nausea, vomiting, and abdominal pain and distension. CT scan of her abdomen reveals segmental ischemia in her colon with abscess formation, which leads to immediate surgery, including ileocecostomy with primary anastomosis. After surgery, Ms. X suffers from gastrointestinal (GI) dysmotility. The gastroenterology team recommends daily enemas along with a soft diet after she is discharged.

Ms. X has chronic paranoid schizophrenia, which has been treated successfully for 18 years with clozapine, 500 mg/d. During acute psychotic episodes, she experienced paranoid delusions and command auditory hallucinations telling her to kill herself. She had previous trials of several antipsychotics, including quetiapine, thiothixene, thioridazine, trifluoperazine, chlorpromazine, and haloperidol, all of which were ineffective and poorly tolerated because of serious side effects.

Within 1 month of discharge, Ms. X returns to the ED with nausea, vomiting, and abdominal distension. Abdominal CT scan suggests partial small bowel obstruction and significantly dilated loops of small bowel with decompressed rectum and sigmoid colon. Considering her recent GI surgery and absence of abdominal pain, she is managed with conservative measures, including nasogastric tube decompression and total parenteral nutrition. CT enterography demonstrates no areas of stricture formation with interval decompression.

The psychiatric service is consulted to evaluate the possibility of clozapine-induced paralytic ileus. During initial assessment, Ms. X denies any psychotic symptoms, including paranoid ideations, delusions, and auditory or visual hallucinations, and firmly believes that clozapine helps keep her stable. She also denies mood symptoms that could indicate mania or depression. She shows no signs or symptoms that suggest anticholinergic delirium.

The authors’ observations

Clozapine has proven efficacy in managing treatment-resistant schizophrenia,^1-3 but the drug has been associated with life-threatening side effects, including agranulocytosis/neutropenia, myocarditis/cardiomyopathy, arrhythmia, seizures, diabetic ketoacidosis, fulminant hepatic failure, pulmonary embolism, and GI complications.⁴

Clozapine-induced GI side effects include anorexia, nausea, vomiting, heartburn, abdominal discomfort, diarrhea, and constipation. Clozapine-induced gastrointestinal hypomotility (CIGH) can lead to fecalith formation, which may result in intestinal obstruction/pseudo-obstruction, intestinal distension, necrosis, perforation, sepsis, aspiration from inhalation of feculent vomitus, or dysphagia.⁵ Constipation has been reported in 14% to 60% of patients who take clozapine,⁶ although other psychiatric medications also can cause constipation (Table 1). Severe constipation can lead to potentially fatal GI complications such as intestinal obstruction, necrosis, perforation, and sepsis, which is associated with significant morbidity due to bowel resection and a 27.5% mortality rate.⁵

The underlying mechanism of clozapine-induced constipation has been well established. The gut is innervated mainly by cholinergic and serotonergic receptors (5-HT3) and these receptors are responsible for peristalsis. Clozapine has a potent anticholinergic effect and acts as a strong antagonist of serotonin receptors (5-HT2, 5-HT3, 5-HT6, 5-HT7), which can lead to gut hypomotility.⁷ Risk factors associated with CIGH include:

• high dose of clozapine (mean dosage >428 mg/d)
• high serum clozapine levels (>500 ng/mL)
• coadministration of anticholinergic medications
• concomitant use of cytochrome P450 (CYP) enzyme inhibitors (medications inhibiting CYP1A2 enzyme)
• comorbid medical illnesses
• fever
• history of surgical bowel resection, GI pathology, and constipation.⁵

Table 1

Psychotropics associated with constipation

HISTORY: Medical comorbidities

Ms. X’s medical history is significant for chronic constipation, hypertension, obstructive pulmonary disease, and hyperthyroidism. Her medications include trazodone, 25 mg/d; fluoxetine, 40 mg/d, for negative symptoms and insomnia; docusate sodium, 200 mg/d; polyethylene glycol, 17 g/d; and bisacodyl suppository, 10 mg as needed for constipation. On admission, her laboratory test results—including complete blood count, liver function tests, kidney function tests, thyroid function profile, and serum calcium levels—all were within normal range.

The authors’ observations

Because the prevalence and severity of clozapine-induced constipation seem to be dose-dependent,⁸ minimizing the dosage is a logical management strategy.⁹ The life-threatening nature of clozapine-induced GI complications may require rapid dose reduction, which could compromise a patient’s stability. There is a little evidence regarding systematic management of clozapine-induced GI complications (Table 2).

Table 2

Clinical pearls for treating clozapine-induced constipation

TREATMENT: Clozapine reduction

We obtain a serum clozapine level, which is elevated at 553 ng/mL. We recommend gradual reducing Ms. X’s clozapine dosage by 50 mg every 3 to 4 days to reach a target dose of 300 to 350 mg/d, to attain serum clozapine levels 350 to 400 ng/mL. Because of trazodone’s potential anticholinergic action, which could be worsening Ms. X’s constipation, we stop the drug and begin zolpidem, 5 to 10 mg/d, to manage her insomnia. During these medication changes, we closely monitor Ms. X for reemerging psychotic symptoms.

The authors’ observations

In addition to risk factors such as chronic constipation and recent GI surgery, Ms. X’s supra-therapeutic serum clozapine level (553 ng/mL) significantly increased her risk of clozapine-induced paralytic ileus. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are known to increase tissue concentrations of clozapine and its major metabolite, norclozapine, by primarily inhibiting CYP1A2 and perhaps CYP2D6.¹⁰ As a potent inhibitor of CYPA12, fluvoxamine can inhibit clozapine metabolism, resulting in higher plasma concentrations.¹¹ In Ms. X’s case, fluoxetine could have increased serum clozapine levels because of its ability to inhibit clozapine metabolism via CYP2D6-mediated mechanisms.¹²

Although clozapine serum levels are not routinely measured, such testing may be indicated in patients who do not respond to or are unable to tolerate clozapine. Clozapine levels should be obtained 12 hours after the bedtime dose (trough levels), several days after clozapine initiation. Serum clozapine levels <350 ng/mL are associated with lack of clinical response.¹³ Higher serum levels (500 to 700 ng/mL) have been associated with greater incidences of serious GI complications. Serum clozapine levels also help guide clozapine dosage reduction because of its linear kinetics—halving the dose will halve the serum clozapine level.¹⁴

OUTCOME: GI symptoms improve

Ms. X shows improved GI motility within few days of the first decrease in her clozapine dosage. Nausea, vomiting, and abdominal distension gradually resolve over 2 weeks with concomitant reduction in clozapine dosage to 300 mg/d (50 mg in the morning and 250 mg at bedtime) without reemergence of psychotic symptoms. She is able to tolerate a soft diet, and conservative GI measures are no longer required. She is discharged home with outpatient surgical and psychiatric follow-up.

The authors’ observations

Successful reversal of severe clozapine-induced constipation—occurring at serum clozapine level of 490 ng/mL—has been reported in a 45-year-old man with treatment-resistant schizophrenia. This was accomplished by cautious reduction of clozapine dosage (400 mg/d to 250 mg/d) over 1 week.¹⁵ Slower clozapine titration—reducing the dose by no more than 25 mg/d to a maximum of 100 mg/week—has been recommended.¹⁶ It also has been suggested to replace part of the clozapine dose with a less antimuscarinic antipsychotic, such as quetiapine or haloperidol, thereby using the second antipsychotic as a clozapine-sparing agent.⁹ For example, the clozapine dose could be reduced by 25% by substituting 2 mg of quetiapine for every 1 mg of clozapine.

Prevention

Psychiatrists who prescribe clozapine should take a careful history of risk factors that might predispose patients to clozapine-induced GI side effects. Caution patients to whom you prescribe clozapine about possible development of constipation and the risk of serious GI complications. Enlist family members and caseworkers to keep a close eye on GI side effects in patients receiving clozapine. Advise patients to prevent constipation by eating a high fiber diet, drinking adequate fluids, and getting regular exercise. Patients should be treated aggressively with laxatives to relieve constipation and educated about the warning signs of intestinal obstruction, such as worsening constipation, abdominal pain, vomiting, and inability to pass flatus.¹⁷

Rapidly fatal bowel ischemia caused by clozapine has been reported.¹⁸ Therefore, urgently refer patients for medical evaluation if you have any concerns about worsening constipation or observe signs of intestinal obstruction. Vigilant consideration of clozapine as a likely culprit in severe GI complications in inpatient settings can prevent morbidity and mortality.

In our case, cautious reduction of clozapine dosage, guided by serum clozapine levels, had obviated the need for surgery and prevented reemergence of psychotic symptoms.

Related Resources

• Drew L, Herdson P. Clozapine and constipation: a serious issue. Aust N Z J Psychiatry. 1997;31(1):149-150.
• Winstead NS, Winstead DK. 5-step plan to treat constipation in psychiatric patients. Current Psychiatry. 2008;7(5):29-39.

Drug Brand Names

• Amitriptyline • Elavil
• Benztropine • Cogentin
• Bisacodyl suppository • Dulcolax, others
• Chlorpromazine • Thorazine
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Docusate sodium • Colace, others
• Doxepin • Adapin, Sinequan
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Nortriptyline • Aventyl, Pamelor
• Pimozide • Orap
• Polyethylene glycol • MiraLax
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel, Oleptro
• Trifluoperazine • Stelazine
• Trihexyphenidyl • Artane, Trihexane
• Trimipramine • Surmontil
• Zolpidem • Ambien

Disclosure

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

Discuss this article at www.facebook.com/CurrentPsychiatry

CASE: Gl surgery

Ms. X, age 61, presents to the emergency department (ED) complaining of nausea, vomiting, and abdominal pain and distension. CT scan of her abdomen reveals segmental ischemia in her colon with abscess formation, which leads to immediate surgery, including ileocecostomy with primary anastomosis. After surgery, Ms. X suffers from gastrointestinal (GI) dysmotility. The gastroenterology team recommends daily enemas along with a soft diet after she is discharged.

Ms. X has chronic paranoid schizophrenia, which has been treated successfully for 18 years with clozapine, 500 mg/d. During acute psychotic episodes, she experienced paranoid delusions and command auditory hallucinations telling her to kill herself. She had previous trials of several antipsychotics, including quetiapine, thiothixene, thioridazine, trifluoperazine, chlorpromazine, and haloperidol, all of which were ineffective and poorly tolerated because of serious side effects.

Within 1 month of discharge, Ms. X returns to the ED with nausea, vomiting, and abdominal distension. Abdominal CT scan suggests partial small bowel obstruction and significantly dilated loops of small bowel with decompressed rectum and sigmoid colon. Considering her recent GI surgery and absence of abdominal pain, she is managed with conservative measures, including nasogastric tube decompression and total parenteral nutrition. CT enterography demonstrates no areas of stricture formation with interval decompression.

The psychiatric service is consulted to evaluate the possibility of clozapine-induced paralytic ileus. During initial assessment, Ms. X denies any psychotic symptoms, including paranoid ideations, delusions, and auditory or visual hallucinations, and firmly believes that clozapine helps keep her stable. She also denies mood symptoms that could indicate mania or depression. She shows no signs or symptoms that suggest anticholinergic delirium.

The authors’ observations

Clozapine has proven efficacy in managing treatment-resistant schizophrenia,^1-3 but the drug has been associated with life-threatening side effects, including agranulocytosis/neutropenia, myocarditis/cardiomyopathy, arrhythmia, seizures, diabetic ketoacidosis, fulminant hepatic failure, pulmonary embolism, and GI complications.⁴

Clozapine-induced GI side effects include anorexia, nausea, vomiting, heartburn, abdominal discomfort, diarrhea, and constipation. Clozapine-induced gastrointestinal hypomotility (CIGH) can lead to fecalith formation, which may result in intestinal obstruction/pseudo-obstruction, intestinal distension, necrosis, perforation, sepsis, aspiration from inhalation of feculent vomitus, or dysphagia.⁵ Constipation has been reported in 14% to 60% of patients who take clozapine,⁶ although other psychiatric medications also can cause constipation (Table 1). Severe constipation can lead to potentially fatal GI complications such as intestinal obstruction, necrosis, perforation, and sepsis, which is associated with significant morbidity due to bowel resection and a 27.5% mortality rate.⁵

The underlying mechanism of clozapine-induced constipation has been well established. The gut is innervated mainly by cholinergic and serotonergic receptors (5-HT3) and these receptors are responsible for peristalsis. Clozapine has a potent anticholinergic effect and acts as a strong antagonist of serotonin receptors (5-HT2, 5-HT3, 5-HT6, 5-HT7), which can lead to gut hypomotility.⁷ Risk factors associated with CIGH include:

• high dose of clozapine (mean dosage >428 mg/d)
• high serum clozapine levels (>500 ng/mL)
• coadministration of anticholinergic medications
• concomitant use of cytochrome P450 (CYP) enzyme inhibitors (medications inhibiting CYP1A2 enzyme)
• comorbid medical illnesses
• fever
• history of surgical bowel resection, GI pathology, and constipation.⁵

Table 1

Psychotropics associated with constipation

HISTORY: Medical comorbidities

Ms. X’s medical history is significant for chronic constipation, hypertension, obstructive pulmonary disease, and hyperthyroidism. Her medications include trazodone, 25 mg/d; fluoxetine, 40 mg/d, for negative symptoms and insomnia; docusate sodium, 200 mg/d; polyethylene glycol, 17 g/d; and bisacodyl suppository, 10 mg as needed for constipation. On admission, her laboratory test results—including complete blood count, liver function tests, kidney function tests, thyroid function profile, and serum calcium levels—all were within normal range.

The authors’ observations

Because the prevalence and severity of clozapine-induced constipation seem to be dose-dependent,⁸ minimizing the dosage is a logical management strategy.⁹ The life-threatening nature of clozapine-induced GI complications may require rapid dose reduction, which could compromise a patient’s stability. There is a little evidence regarding systematic management of clozapine-induced GI complications (Table 2).

Table 2

Clinical pearls for treating clozapine-induced constipation

TREATMENT: Clozapine reduction

We obtain a serum clozapine level, which is elevated at 553 ng/mL. We recommend gradual reducing Ms. X’s clozapine dosage by 50 mg every 3 to 4 days to reach a target dose of 300 to 350 mg/d, to attain serum clozapine levels 350 to 400 ng/mL. Because of trazodone’s potential anticholinergic action, which could be worsening Ms. X’s constipation, we stop the drug and begin zolpidem, 5 to 10 mg/d, to manage her insomnia. During these medication changes, we closely monitor Ms. X for reemerging psychotic symptoms.

The authors’ observations

In addition to risk factors such as chronic constipation and recent GI surgery, Ms. X’s supra-therapeutic serum clozapine level (553 ng/mL) significantly increased her risk of clozapine-induced paralytic ileus. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are known to increase tissue concentrations of clozapine and its major metabolite, norclozapine, by primarily inhibiting CYP1A2 and perhaps CYP2D6.¹⁰ As a potent inhibitor of CYPA12, fluvoxamine can inhibit clozapine metabolism, resulting in higher plasma concentrations.¹¹ In Ms. X’s case, fluoxetine could have increased serum clozapine levels because of its ability to inhibit clozapine metabolism via CYP2D6-mediated mechanisms.¹²

Although clozapine serum levels are not routinely measured, such testing may be indicated in patients who do not respond to or are unable to tolerate clozapine. Clozapine levels should be obtained 12 hours after the bedtime dose (trough levels), several days after clozapine initiation. Serum clozapine levels <350 ng/mL are associated with lack of clinical response.¹³ Higher serum levels (500 to 700 ng/mL) have been associated with greater incidences of serious GI complications. Serum clozapine levels also help guide clozapine dosage reduction because of its linear kinetics—halving the dose will halve the serum clozapine level.¹⁴

OUTCOME: GI symptoms improve

Ms. X shows improved GI motility within few days of the first decrease in her clozapine dosage. Nausea, vomiting, and abdominal distension gradually resolve over 2 weeks with concomitant reduction in clozapine dosage to 300 mg/d (50 mg in the morning and 250 mg at bedtime) without reemergence of psychotic symptoms. She is able to tolerate a soft diet, and conservative GI measures are no longer required. She is discharged home with outpatient surgical and psychiatric follow-up.

The authors’ observations

Successful reversal of severe clozapine-induced constipation—occurring at serum clozapine level of 490 ng/mL—has been reported in a 45-year-old man with treatment-resistant schizophrenia. This was accomplished by cautious reduction of clozapine dosage (400 mg/d to 250 mg/d) over 1 week.¹⁵ Slower clozapine titration—reducing the dose by no more than 25 mg/d to a maximum of 100 mg/week—has been recommended.¹⁶ It also has been suggested to replace part of the clozapine dose with a less antimuscarinic antipsychotic, such as quetiapine or haloperidol, thereby using the second antipsychotic as a clozapine-sparing agent.⁹ For example, the clozapine dose could be reduced by 25% by substituting 2 mg of quetiapine for every 1 mg of clozapine.

Prevention

Psychiatrists who prescribe clozapine should take a careful history of risk factors that might predispose patients to clozapine-induced GI side effects. Caution patients to whom you prescribe clozapine about possible development of constipation and the risk of serious GI complications. Enlist family members and caseworkers to keep a close eye on GI side effects in patients receiving clozapine. Advise patients to prevent constipation by eating a high fiber diet, drinking adequate fluids, and getting regular exercise. Patients should be treated aggressively with laxatives to relieve constipation and educated about the warning signs of intestinal obstruction, such as worsening constipation, abdominal pain, vomiting, and inability to pass flatus.¹⁷

Rapidly fatal bowel ischemia caused by clozapine has been reported.¹⁸ Therefore, urgently refer patients for medical evaluation if you have any concerns about worsening constipation or observe signs of intestinal obstruction. Vigilant consideration of clozapine as a likely culprit in severe GI complications in inpatient settings can prevent morbidity and mortality.

In our case, cautious reduction of clozapine dosage, guided by serum clozapine levels, had obviated the need for surgery and prevented reemergence of psychotic symptoms.

Related Resources

• Drew L, Herdson P. Clozapine and constipation: a serious issue. Aust N Z J Psychiatry. 1997;31(1):149-150.
• Winstead NS, Winstead DK. 5-step plan to treat constipation in psychiatric patients. Current Psychiatry. 2008;7(5):29-39.

Drug Brand Names

• Amitriptyline • Elavil
• Benztropine • Cogentin
• Bisacodyl suppository • Dulcolax, others
• Chlorpromazine • Thorazine
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Docusate sodium • Colace, others
• Doxepin • Adapin, Sinequan
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Nortriptyline • Aventyl, Pamelor
• Pimozide • Orap
• Polyethylene glycol • MiraLax
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel, Oleptro
• Trifluoperazine • Stelazine
• Trihexyphenidyl • Artane, Trihexane
• Trimipramine • Surmontil
• Zolpidem • Ambien

Disclosure

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

CASE: Agitated and paranoid

Police bring Mr. L, age 85, to the emergency department (ED) because he threatened his wife, claiming she is having an affair. Two days earlier, he was discharged from a different hospital, where he was treated for progressive and fluctuating irritability, depressed mood, confusion, disorientation, inattention, and delusional thinking that had started 4 to 5 months earlier. He has no other psychiatric history.

Mr. L has a history of atrial fibrillation, hypertension, benign prostatic hypertrophy, and noninsulin-dependent diabetes mellitus. Several months ago, he had hip surgery, which was complicated by a surgical wound infection. Medications include digoxin, 0.125 mg/d; atenolol, 100 mg/d; warfarin, 1 mg/d on Monday, Wednesday, Friday, Saturday, and Sunday and 0.5 mg/d Tuesday and Thursday; lisinopril, 40 mg/d; tamsulosin, 0.4 mg/d; and glyburide, 1.25 mg/d. During the previous hospitalization, physicians discovered he had myasthenia gravis, which they treated with prednisone and pyridostigmine. Mr. L also was diagnosed with hyperaldosteronism. An adrenal mass was found in an abdominal CT. At that time, he also was diagnosed with major depressive disorder (MDD) with psychotic features and started on aripiprazole, 10 mg/d, mirtazapine, 30 mg/d, and trazodone, 50 mg/d for sleep.

The authors’ observations

When evaluating mental status changes in older patients, consider the time course and characteristics of the changes, especially if the patient’s cognitive function changes. Acute mental status changes that occur over hours to days often represent delirium caused by a medical condition such as a coronary event or infection. Changes that develop over weeks to months often signal a primary psychiatric disorder such as depression, mania, or dementia. Mr. L’s mood and psychotic symptoms developed over 4 to 5 months and were thought to be a result of MDD with psychotic features. However, his fluctuating cognitive symptoms, confusion, and lack of psychiatric history suggest that the differential diagnosis should include a cognitive disorder such as delirium or dementia. The hypoactive form of delirium often is unrecognized or misdiagnosed as sedation or depression, particularly in older patients.¹

Multiple medical conditions and polypharmacy are important factors to consider when evaluating mental status changes in geriatric patients. In Mr. L’s case, atrial fibrillation, hypertension, and diabetes increase his risk of an acute cardiovascular or cerebrovascular event and chronic cerebrovascular disease. Hyperaldosteronism can lead to electrolyte abnormalities that may produce mental status changes. Treatment with an oral hypoglycemic raises the possibility that hypoglycemia is contributing to his mental status changes. Prednisone can cause psychosis, anxiety, and mania. Digoxin toxicity is associated with psychosis and irritability. Pyridostigmine also has been reported to cause psychosis. Use of an antidepressant, such as mirtazapine, could have exacerbated an underlying undiagnosed bipolar disorder. Antipsychotics, such as aripiprazole, may cause akathisia or activation. Substance intoxication or withdrawal should not be excluded solely because a patient is older. In older patients, medications with anti-cholinergic effects are common culprits for cognitive impairment (Table 1).^2,3

Table 1

Medications that could contribute to mental status changes

ASSESSMENT: More problems

At admission to the medical unit, Mr. L’s temperature is 36.7°C (98°F), with a heart rate of 77 beats per minute, respiratory rate of 24 breaths per minute, and blood pressure of 164/84 mm Hg with oxygen saturation of 96% at room air. Physical exam is notable for 2+ pitting edema in the lower extremities. Mr. L is oriented to person, place, and time and is psychomotorically activated. Neurologic examination is within normal limits.

Laboratory data reveal a potassium level of 2.5 mEq/L. Other results, including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, urinalysis, urine toxicology screen, B12, folate, venereal disease research laboratory, and ammonia are unremarkable. Chest radiography reveals an enlarged cardiomediastinum. A CT scan of the brain without contrast shows cortical volume loss and periventricular white matter disease without evidence of acute intracranial abnormality. ECG shows atrial fibrillation with a rate of 67 beats per minute.

Mr. L’s hypokalemia is corrected with potassium chloride and his hyperaldosteronism is treated with spironolactone, 25 mg/d. Physicians on the medical unit discontinue digoxin because Mr. L’s heart rate is controlled with atenolol and he is anticoagulated with warfarin.

Mr. L continues to be depressed and irritable with delusional jealousy. Mirtazapine is continued at 30 mg/d at bedtime. Aripiprazole and trazodone are discontinued and Mr. L is started on olanzapine, 10 mg/d, and haloperidol, 1 mg 4 times a day as needed for agitation. He requires multiple “as needed” haloperidol doses because of intermittent episodes of agitation. Mr. L is then transferred to the inpatient psychiatric unit for continued evaluation and treatment.

The authors’ observations

The fact that Mr. L is alert and oriented is encouraging; however, it does not rule out delirium because this condition is characterized by fluctuating levels of consciousness. Therefore, it is important to reassess him over time and perform a more thorough evaluation of cognitive function, especially attention and concentration, in addition to alertness and orientation. Psychomotor activation could suggest agitated depression, anxiety, mania, psychosis, substance intoxication, akathisia from antipsychotics, or delirium (Table 2).⁴ Initial evaluation— especially in older patients—should include a thorough history (including collateral sources) and be guided by the clinical presentation and physical examination, taking into consideration life-threatening conditions and common causes of mental status change such as infections, hypoxia, substance or medication effects, acute coronary syndromes, acute neurologic events, and metabolic conditions.

Table 2

DSM-IV-TR criteria for delirium caused by a medical condition

Reconsider the diagnosis

Even after being treated for hyperaldosteronism and discontinuing unnecessary medications, Mr. L continued to be treated for MDD with psychotic features despite intermittent confusion and agitation. At this point, it might have been useful to reconsider whether MDD with psychotic features was the most appropriate diagnosis to explain his mental status changes.

Mental status changes caused by medical disorders or medications do not immediately clear after the medical disorder is corrected or the medication is discontinued; it could take days or weeks for a patient to return to baseline. In Mr. L’s case it may be useful to simplify his medication regimen because polypharmacy contributes to delirium. Finally, olanzapine could worsen his condition because of its anticholinergic effects.⁵

EVALUATION: Poor cognitive status

Mental status examination upon admission to the psychiatric unit reveals a poorly cooperative patient with irritable mood and affect with slowed psychomotor activity. Mr. L’s thought process is organized with normal associations and thought content does not reveal suicidality or homicidality. However, he verbalizes delusions about his wife having an affair with a neighbor. He is partially oriented to time but believes he is in Germany. His insight is limited and he demonstrates impaired attention and concentration. We cannot complete a Mini-Mental State Exam (MMSE) because Mr. L does not cooperate.

After admission, Mr. L is intermittently confused, agitated, and disoriented. Between these episodes he is pleasant, cooperative, and oriented. Jealous delusions regarding his wife continue. Olanzapine and mirtazapine are tapered and discontinued. Haloperidol dose is changed to 1 mg 3 times a day, then to 1.5 mg in the morning and 3 mg in the evening. Prednisone is tapered and discontinued.

The authors’ observations

Cognitive testing is essential for the diagnosis and treatment of patients with mental status changes and for evaluating their response to treatment. Although the MMSE is widely used, other scales—including the Confusion Assessment Method, the Organic Brain Syndrome Scale, the Memorial Delirium Assessment Scale, and the delirium severity index⁶—may be more sensitive for detecting delirium. All of these scales can be difficult to complete when evaluating confused and combative patients. Quick screening instruments for inattention, such as the digit span test and listing days of the week backwards, could be used as well.

HISTORY: Surgical complications

Further questioning of Mr. L’s family reveals that his behavior started to change 7 months ago; this was 1 month after undergoing hip replacement surgery, which was complicated by a surgical wound infection and worsened his medical illnesses. Within a month, Mr. L became withdrawn and appeared depressed. He was confused and intermittently disoriented to place and time. He became irritable and started reporting concerns about his wife having an affair. During this time different medications were introduced, including steroids and several antibiotics.

The authors’ observations

A thorough history from the patient and caregivers, including the time course of mental status changes, new medication use, and history of medical and psychiatric disorders—especially depression and dementia—are important to obtain, especially early in the evaluation.

Although Mr. L’s irritability, delusions, and psychomotor slowing could be signs of psychotic depression, his fluctuating mental status, disorientation, poor attention, and impaired concentration suggest delirium (Table 3).^4,7 This diagnosis is supported by the fact that Mr. L’s symptoms emerged after orthopedic surgery. Delirium after orthopedic surgery is common among older patients.⁸ Contributing and perpetuating factors in Mr. L’s case may have included postoperative complications, hypokalemia (hyperaldosteronism), medications (prednisone, digoxin, and olanzapine), and environmental unfamiliarity during hospitalization. A delirium diagnosis should be based on a high index of suspicion and a careful clinical assessment rather than diagnostic tests.

Table 3

Deconstructing delirium

OUTCOME: Return home

Mr. L’s confusion and delusional jealousy decrease over time, as do his disorientation and inattention, as evidenced by improvement on MMSE scores. His last MMSE score is 27/30, failing mostly in attention and recall.

After sustained improvement in cognition and behavior, Mr. L is discharged home on haloperidol and the remainder of his nonpsychiatric medications with outpatient medical and psychiatric follow-up. Over several months, he continues to show improvement and haloperidol is discontinued.

The authors’ observations

Delirium treatment should focus on prompt identification and management of precipitating and contributing factors.⁷ Antipsychotics are considered first-line treatment for patients with delirium, agitation, or psychosis who pose a risk to themselves or others. Benzodiazepines should be avoided in older patients unless symptoms are secondary to CNS-depressant withdrawal (ie, alcohol, benzodiazepines).⁹

Although there are no-FDA approved medications for delirium, haloperidol has been widely studied and used for treatment of agitation and psychosis in delirium. There is no evidence that low-dose haloperidol is any less effective than olanzapine or risperidone, or is more likely to cause adverse drug effects such as extrapyramidal syndrome.¹⁰ Antipsychotic use in a confused or agitated dementia patient increases risk of mortality compared with dementia patients who do not receive antipsychotics.¹¹ The use of typical or atypical antipsychotics for delirium should be guided by the patient’s characteristics, such as cardiovascular status and presence or absence of underlying dementia. Atypical antipsychotics should be used carefully because—as in Mr. L’s case—anticholinergic side effects of medications such as olanzapine could worsen delirium.⁵ Once delirium has resolved, antipsychotics should be tapered and discontinued.

Other components of delirium treatment and prevention include:

• reorientation (verbally, with clocks, calendars, etc.)
• safe ambulation
• adequate sleep, food, and fluid intake
• adaptive equipment for vision and hearing impairment
• adequate management of pain and other comorbidities.¹²

Related Resources

• Khan RA, Kahn D, Bourgeois JA. Delirium: sifting through the confusion. Curr Psychiatry Rep. 2009;11(3):226-234.
• Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis, and treatment. Crit Care Clin. 2008;24:657-722.
• Young J, Inouye SK. Delirium in older people. BMJ. 2007;334(7598):842-846.

Drug Brand Names

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Atenolol • Tenormin
• Atropine • AtroPen
• Benztropine • Cogentin
• Cimetidine • Tagamet
• Clozapine • Clozaril
• Digoxin • Lanoxicaps, Lanoxin
• Glyburide • DiaBeta, Micronase
• Haloperidol • Haldol
• Levodopa/carbidopa • Parcopa, Sinemet
• Lisinopril • Prinivil, Zestril
• Lorazepam • Ativan
• Meperidine • Demerol
• Mirtazapine • Remeron
• Olanzapine • Zyprexa
• Omeprazole • Prilosec
• Oxybutynin • Ditropan
• Pergolide • Permax
• Phenytoin • Dilantin, Phenytek
• Prednisolone • Orapred, Prelone, others
• Prednisone • Deltasone, Meticorten
• Pyridostigmine • Mestinon
• Ranitidine • Zantac
• Risperidone • Risperdal
• Selegiline • Eldepryl, Zelapar
• Spironolactone • Aldactone
• Tamsulosin • Flomax
• Thioridazine • Mellaril
• Trazodone • Desyrel
• Warfarin • Coumadin

Disclosure

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

CASE: Agitated and paranoid

Police bring Mr. L, age 85, to the emergency department (ED) because he threatened his wife, claiming she is having an affair. Two days earlier, he was discharged from a different hospital, where he was treated for progressive and fluctuating irritability, depressed mood, confusion, disorientation, inattention, and delusional thinking that had started 4 to 5 months earlier. He has no other psychiatric history.

Mr. L has a history of atrial fibrillation, hypertension, benign prostatic hypertrophy, and noninsulin-dependent diabetes mellitus. Several months ago, he had hip surgery, which was complicated by a surgical wound infection. Medications include digoxin, 0.125 mg/d; atenolol, 100 mg/d; warfarin, 1 mg/d on Monday, Wednesday, Friday, Saturday, and Sunday and 0.5 mg/d Tuesday and Thursday; lisinopril, 40 mg/d; tamsulosin, 0.4 mg/d; and glyburide, 1.25 mg/d. During the previous hospitalization, physicians discovered he had myasthenia gravis, which they treated with prednisone and pyridostigmine. Mr. L also was diagnosed with hyperaldosteronism. An adrenal mass was found in an abdominal CT. At that time, he also was diagnosed with major depressive disorder (MDD) with psychotic features and started on aripiprazole, 10 mg/d, mirtazapine, 30 mg/d, and trazodone, 50 mg/d for sleep.

The authors’ observations

When evaluating mental status changes in older patients, consider the time course and characteristics of the changes, especially if the patient’s cognitive function changes. Acute mental status changes that occur over hours to days often represent delirium caused by a medical condition such as a coronary event or infection. Changes that develop over weeks to months often signal a primary psychiatric disorder such as depression, mania, or dementia. Mr. L’s mood and psychotic symptoms developed over 4 to 5 months and were thought to be a result of MDD with psychotic features. However, his fluctuating cognitive symptoms, confusion, and lack of psychiatric history suggest that the differential diagnosis should include a cognitive disorder such as delirium or dementia. The hypoactive form of delirium often is unrecognized or misdiagnosed as sedation or depression, particularly in older patients.¹

Multiple medical conditions and polypharmacy are important factors to consider when evaluating mental status changes in geriatric patients. In Mr. L’s case, atrial fibrillation, hypertension, and diabetes increase his risk of an acute cardiovascular or cerebrovascular event and chronic cerebrovascular disease. Hyperaldosteronism can lead to electrolyte abnormalities that may produce mental status changes. Treatment with an oral hypoglycemic raises the possibility that hypoglycemia is contributing to his mental status changes. Prednisone can cause psychosis, anxiety, and mania. Digoxin toxicity is associated with psychosis and irritability. Pyridostigmine also has been reported to cause psychosis. Use of an antidepressant, such as mirtazapine, could have exacerbated an underlying undiagnosed bipolar disorder. Antipsychotics, such as aripiprazole, may cause akathisia or activation. Substance intoxication or withdrawal should not be excluded solely because a patient is older. In older patients, medications with anti-cholinergic effects are common culprits for cognitive impairment (Table 1).^2,3

Table 1

Medications that could contribute to mental status changes

ASSESSMENT: More problems

At admission to the medical unit, Mr. L’s temperature is 36.7°C (98°F), with a heart rate of 77 beats per minute, respiratory rate of 24 breaths per minute, and blood pressure of 164/84 mm Hg with oxygen saturation of 96% at room air. Physical exam is notable for 2+ pitting edema in the lower extremities. Mr. L is oriented to person, place, and time and is psychomotorically activated. Neurologic examination is within normal limits.

Laboratory data reveal a potassium level of 2.5 mEq/L. Other results, including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, urinalysis, urine toxicology screen, B12, folate, venereal disease research laboratory, and ammonia are unremarkable. Chest radiography reveals an enlarged cardiomediastinum. A CT scan of the brain without contrast shows cortical volume loss and periventricular white matter disease without evidence of acute intracranial abnormality. ECG shows atrial fibrillation with a rate of 67 beats per minute.

Mr. L’s hypokalemia is corrected with potassium chloride and his hyperaldosteronism is treated with spironolactone, 25 mg/d. Physicians on the medical unit discontinue digoxin because Mr. L’s heart rate is controlled with atenolol and he is anticoagulated with warfarin.

Mr. L continues to be depressed and irritable with delusional jealousy. Mirtazapine is continued at 30 mg/d at bedtime. Aripiprazole and trazodone are discontinued and Mr. L is started on olanzapine, 10 mg/d, and haloperidol, 1 mg 4 times a day as needed for agitation. He requires multiple “as needed” haloperidol doses because of intermittent episodes of agitation. Mr. L is then transferred to the inpatient psychiatric unit for continued evaluation and treatment.

The authors’ observations

The fact that Mr. L is alert and oriented is encouraging; however, it does not rule out delirium because this condition is characterized by fluctuating levels of consciousness. Therefore, it is important to reassess him over time and perform a more thorough evaluation of cognitive function, especially attention and concentration, in addition to alertness and orientation. Psychomotor activation could suggest agitated depression, anxiety, mania, psychosis, substance intoxication, akathisia from antipsychotics, or delirium (Table 2).⁴ Initial evaluation— especially in older patients—should include a thorough history (including collateral sources) and be guided by the clinical presentation and physical examination, taking into consideration life-threatening conditions and common causes of mental status change such as infections, hypoxia, substance or medication effects, acute coronary syndromes, acute neurologic events, and metabolic conditions.

Table 2

DSM-IV-TR criteria for delirium caused by a medical condition

Reconsider the diagnosis

Even after being treated for hyperaldosteronism and discontinuing unnecessary medications, Mr. L continued to be treated for MDD with psychotic features despite intermittent confusion and agitation. At this point, it might have been useful to reconsider whether MDD with psychotic features was the most appropriate diagnosis to explain his mental status changes.

Mental status changes caused by medical disorders or medications do not immediately clear after the medical disorder is corrected or the medication is discontinued; it could take days or weeks for a patient to return to baseline. In Mr. L’s case it may be useful to simplify his medication regimen because polypharmacy contributes to delirium. Finally, olanzapine could worsen his condition because of its anticholinergic effects.⁵

EVALUATION: Poor cognitive status

Mental status examination upon admission to the psychiatric unit reveals a poorly cooperative patient with irritable mood and affect with slowed psychomotor activity. Mr. L’s thought process is organized with normal associations and thought content does not reveal suicidality or homicidality. However, he verbalizes delusions about his wife having an affair with a neighbor. He is partially oriented to time but believes he is in Germany. His insight is limited and he demonstrates impaired attention and concentration. We cannot complete a Mini-Mental State Exam (MMSE) because Mr. L does not cooperate.

After admission, Mr. L is intermittently confused, agitated, and disoriented. Between these episodes he is pleasant, cooperative, and oriented. Jealous delusions regarding his wife continue. Olanzapine and mirtazapine are tapered and discontinued. Haloperidol dose is changed to 1 mg 3 times a day, then to 1.5 mg in the morning and 3 mg in the evening. Prednisone is tapered and discontinued.

The authors’ observations

Cognitive testing is essential for the diagnosis and treatment of patients with mental status changes and for evaluating their response to treatment. Although the MMSE is widely used, other scales—including the Confusion Assessment Method, the Organic Brain Syndrome Scale, the Memorial Delirium Assessment Scale, and the delirium severity index⁶—may be more sensitive for detecting delirium. All of these scales can be difficult to complete when evaluating confused and combative patients. Quick screening instruments for inattention, such as the digit span test and listing days of the week backwards, could be used as well.

HISTORY: Surgical complications

Further questioning of Mr. L’s family reveals that his behavior started to change 7 months ago; this was 1 month after undergoing hip replacement surgery, which was complicated by a surgical wound infection and worsened his medical illnesses. Within a month, Mr. L became withdrawn and appeared depressed. He was confused and intermittently disoriented to place and time. He became irritable and started reporting concerns about his wife having an affair. During this time different medications were introduced, including steroids and several antibiotics.

The authors’ observations

A thorough history from the patient and caregivers, including the time course of mental status changes, new medication use, and history of medical and psychiatric disorders—especially depression and dementia—are important to obtain, especially early in the evaluation.

Although Mr. L’s irritability, delusions, and psychomotor slowing could be signs of psychotic depression, his fluctuating mental status, disorientation, poor attention, and impaired concentration suggest delirium (Table 3).^4,7 This diagnosis is supported by the fact that Mr. L’s symptoms emerged after orthopedic surgery. Delirium after orthopedic surgery is common among older patients.⁸ Contributing and perpetuating factors in Mr. L’s case may have included postoperative complications, hypokalemia (hyperaldosteronism), medications (prednisone, digoxin, and olanzapine), and environmental unfamiliarity during hospitalization. A delirium diagnosis should be based on a high index of suspicion and a careful clinical assessment rather than diagnostic tests.

Table 3

Deconstructing delirium

OUTCOME: Return home

Mr. L’s confusion and delusional jealousy decrease over time, as do his disorientation and inattention, as evidenced by improvement on MMSE scores. His last MMSE score is 27/30, failing mostly in attention and recall.

After sustained improvement in cognition and behavior, Mr. L is discharged home on haloperidol and the remainder of his nonpsychiatric medications with outpatient medical and psychiatric follow-up. Over several months, he continues to show improvement and haloperidol is discontinued.

The authors’ observations

Delirium treatment should focus on prompt identification and management of precipitating and contributing factors.⁷ Antipsychotics are considered first-line treatment for patients with delirium, agitation, or psychosis who pose a risk to themselves or others. Benzodiazepines should be avoided in older patients unless symptoms are secondary to CNS-depressant withdrawal (ie, alcohol, benzodiazepines).⁹

Although there are no-FDA approved medications for delirium, haloperidol has been widely studied and used for treatment of agitation and psychosis in delirium. There is no evidence that low-dose haloperidol is any less effective than olanzapine or risperidone, or is more likely to cause adverse drug effects such as extrapyramidal syndrome.¹⁰ Antipsychotic use in a confused or agitated dementia patient increases risk of mortality compared with dementia patients who do not receive antipsychotics.¹¹ The use of typical or atypical antipsychotics for delirium should be guided by the patient’s characteristics, such as cardiovascular status and presence or absence of underlying dementia. Atypical antipsychotics should be used carefully because—as in Mr. L’s case—anticholinergic side effects of medications such as olanzapine could worsen delirium.⁵ Once delirium has resolved, antipsychotics should be tapered and discontinued.

Other components of delirium treatment and prevention include:

• reorientation (verbally, with clocks, calendars, etc.)
• safe ambulation
• adequate sleep, food, and fluid intake
• adaptive equipment for vision and hearing impairment
• adequate management of pain and other comorbidities.¹²

Related Resources

• Khan RA, Kahn D, Bourgeois JA. Delirium: sifting through the confusion. Curr Psychiatry Rep. 2009;11(3):226-234.
• Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis, and treatment. Crit Care Clin. 2008;24:657-722.
• Young J, Inouye SK. Delirium in older people. BMJ. 2007;334(7598):842-846.

Drug Brand Names

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Atenolol • Tenormin
• Atropine • AtroPen
• Benztropine • Cogentin
• Cimetidine • Tagamet
• Clozapine • Clozaril
• Digoxin • Lanoxicaps, Lanoxin
• Glyburide • DiaBeta, Micronase
• Haloperidol • Haldol
• Levodopa/carbidopa • Parcopa, Sinemet
• Lisinopril • Prinivil, Zestril
• Lorazepam • Ativan
• Meperidine • Demerol
• Mirtazapine • Remeron
• Olanzapine • Zyprexa
• Omeprazole • Prilosec
• Oxybutynin • Ditropan
• Pergolide • Permax
• Phenytoin • Dilantin, Phenytek
• Prednisolone • Orapred, Prelone, others
• Prednisone • Deltasone, Meticorten
• Pyridostigmine • Mestinon
• Ranitidine • Zantac
• Risperidone • Risperdal
• Selegiline • Eldepryl, Zelapar
• Spironolactone • Aldactone
• Tamsulosin • Flomax
• Thioridazine • Mellaril
• Trazodone • Desyrel
• Warfarin • Coumadin

Disclosure

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

CASE: Agitated and paranoid

Police bring Mr. L, age 85, to the emergency department (ED) because he threatened his wife, claiming she is having an affair. Two days earlier, he was discharged from a different hospital, where he was treated for progressive and fluctuating irritability, depressed mood, confusion, disorientation, inattention, and delusional thinking that had started 4 to 5 months earlier. He has no other psychiatric history.

Mr. L has a history of atrial fibrillation, hypertension, benign prostatic hypertrophy, and noninsulin-dependent diabetes mellitus. Several months ago, he had hip surgery, which was complicated by a surgical wound infection. Medications include digoxin, 0.125 mg/d; atenolol, 100 mg/d; warfarin, 1 mg/d on Monday, Wednesday, Friday, Saturday, and Sunday and 0.5 mg/d Tuesday and Thursday; lisinopril, 40 mg/d; tamsulosin, 0.4 mg/d; and glyburide, 1.25 mg/d. During the previous hospitalization, physicians discovered he had myasthenia gravis, which they treated with prednisone and pyridostigmine. Mr. L also was diagnosed with hyperaldosteronism. An adrenal mass was found in an abdominal CT. At that time, he also was diagnosed with major depressive disorder (MDD) with psychotic features and started on aripiprazole, 10 mg/d, mirtazapine, 30 mg/d, and trazodone, 50 mg/d for sleep.

The authors’ observations

When evaluating mental status changes in older patients, consider the time course and characteristics of the changes, especially if the patient’s cognitive function changes. Acute mental status changes that occur over hours to days often represent delirium caused by a medical condition such as a coronary event or infection. Changes that develop over weeks to months often signal a primary psychiatric disorder such as depression, mania, or dementia. Mr. L’s mood and psychotic symptoms developed over 4 to 5 months and were thought to be a result of MDD with psychotic features. However, his fluctuating cognitive symptoms, confusion, and lack of psychiatric history suggest that the differential diagnosis should include a cognitive disorder such as delirium or dementia. The hypoactive form of delirium often is unrecognized or misdiagnosed as sedation or depression, particularly in older patients.¹

Multiple medical conditions and polypharmacy are important factors to consider when evaluating mental status changes in geriatric patients. In Mr. L’s case, atrial fibrillation, hypertension, and diabetes increase his risk of an acute cardiovascular or cerebrovascular event and chronic cerebrovascular disease. Hyperaldosteronism can lead to electrolyte abnormalities that may produce mental status changes. Treatment with an oral hypoglycemic raises the possibility that hypoglycemia is contributing to his mental status changes. Prednisone can cause psychosis, anxiety, and mania. Digoxin toxicity is associated with psychosis and irritability. Pyridostigmine also has been reported to cause psychosis. Use of an antidepressant, such as mirtazapine, could have exacerbated an underlying undiagnosed bipolar disorder. Antipsychotics, such as aripiprazole, may cause akathisia or activation. Substance intoxication or withdrawal should not be excluded solely because a patient is older. In older patients, medications with anti-cholinergic effects are common culprits for cognitive impairment (Table 1).^2,3

Table 1

Medications that could contribute to mental status changes

ASSESSMENT: More problems

At admission to the medical unit, Mr. L’s temperature is 36.7°C (98°F), with a heart rate of 77 beats per minute, respiratory rate of 24 breaths per minute, and blood pressure of 164/84 mm Hg with oxygen saturation of 96% at room air. Physical exam is notable for 2+ pitting edema in the lower extremities. Mr. L is oriented to person, place, and time and is psychomotorically activated. Neurologic examination is within normal limits.

Laboratory data reveal a potassium level of 2.5 mEq/L. Other results, including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, urinalysis, urine toxicology screen, B12, folate, venereal disease research laboratory, and ammonia are unremarkable. Chest radiography reveals an enlarged cardiomediastinum. A CT scan of the brain without contrast shows cortical volume loss and periventricular white matter disease without evidence of acute intracranial abnormality. ECG shows atrial fibrillation with a rate of 67 beats per minute.

Mr. L’s hypokalemia is corrected with potassium chloride and his hyperaldosteronism is treated with spironolactone, 25 mg/d. Physicians on the medical unit discontinue digoxin because Mr. L’s heart rate is controlled with atenolol and he is anticoagulated with warfarin.

Mr. L continues to be depressed and irritable with delusional jealousy. Mirtazapine is continued at 30 mg/d at bedtime. Aripiprazole and trazodone are discontinued and Mr. L is started on olanzapine, 10 mg/d, and haloperidol, 1 mg 4 times a day as needed for agitation. He requires multiple “as needed” haloperidol doses because of intermittent episodes of agitation. Mr. L is then transferred to the inpatient psychiatric unit for continued evaluation and treatment.

The authors’ observations

The fact that Mr. L is alert and oriented is encouraging; however, it does not rule out delirium because this condition is characterized by fluctuating levels of consciousness. Therefore, it is important to reassess him over time and perform a more thorough evaluation of cognitive function, especially attention and concentration, in addition to alertness and orientation. Psychomotor activation could suggest agitated depression, anxiety, mania, psychosis, substance intoxication, akathisia from antipsychotics, or delirium (Table 2).⁴ Initial evaluation— especially in older patients—should include a thorough history (including collateral sources) and be guided by the clinical presentation and physical examination, taking into consideration life-threatening conditions and common causes of mental status change such as infections, hypoxia, substance or medication effects, acute coronary syndromes, acute neurologic events, and metabolic conditions.

Table 2

DSM-IV-TR criteria for delirium caused by a medical condition

Reconsider the diagnosis

Even after being treated for hyperaldosteronism and discontinuing unnecessary medications, Mr. L continued to be treated for MDD with psychotic features despite intermittent confusion and agitation. At this point, it might have been useful to reconsider whether MDD with psychotic features was the most appropriate diagnosis to explain his mental status changes.

Mental status changes caused by medical disorders or medications do not immediately clear after the medical disorder is corrected or the medication is discontinued; it could take days or weeks for a patient to return to baseline. In Mr. L’s case it may be useful to simplify his medication regimen because polypharmacy contributes to delirium. Finally, olanzapine could worsen his condition because of its anticholinergic effects.⁵

EVALUATION: Poor cognitive status

Mental status examination upon admission to the psychiatric unit reveals a poorly cooperative patient with irritable mood and affect with slowed psychomotor activity. Mr. L’s thought process is organized with normal associations and thought content does not reveal suicidality or homicidality. However, he verbalizes delusions about his wife having an affair with a neighbor. He is partially oriented to time but believes he is in Germany. His insight is limited and he demonstrates impaired attention and concentration. We cannot complete a Mini-Mental State Exam (MMSE) because Mr. L does not cooperate.

After admission, Mr. L is intermittently confused, agitated, and disoriented. Between these episodes he is pleasant, cooperative, and oriented. Jealous delusions regarding his wife continue. Olanzapine and mirtazapine are tapered and discontinued. Haloperidol dose is changed to 1 mg 3 times a day, then to 1.5 mg in the morning and 3 mg in the evening. Prednisone is tapered and discontinued.

The authors’ observations

Cognitive testing is essential for the diagnosis and treatment of patients with mental status changes and for evaluating their response to treatment. Although the MMSE is widely used, other scales—including the Confusion Assessment Method, the Organic Brain Syndrome Scale, the Memorial Delirium Assessment Scale, and the delirium severity index⁶—may be more sensitive for detecting delirium. All of these scales can be difficult to complete when evaluating confused and combative patients. Quick screening instruments for inattention, such as the digit span test and listing days of the week backwards, could be used as well.

HISTORY: Surgical complications

Further questioning of Mr. L’s family reveals that his behavior started to change 7 months ago; this was 1 month after undergoing hip replacement surgery, which was complicated by a surgical wound infection and worsened his medical illnesses. Within a month, Mr. L became withdrawn and appeared depressed. He was confused and intermittently disoriented to place and time. He became irritable and started reporting concerns about his wife having an affair. During this time different medications were introduced, including steroids and several antibiotics.

The authors’ observations

A thorough history from the patient and caregivers, including the time course of mental status changes, new medication use, and history of medical and psychiatric disorders—especially depression and dementia—are important to obtain, especially early in the evaluation.

Although Mr. L’s irritability, delusions, and psychomotor slowing could be signs of psychotic depression, his fluctuating mental status, disorientation, poor attention, and impaired concentration suggest delirium (Table 3).^4,7 This diagnosis is supported by the fact that Mr. L’s symptoms emerged after orthopedic surgery. Delirium after orthopedic surgery is common among older patients.⁸ Contributing and perpetuating factors in Mr. L’s case may have included postoperative complications, hypokalemia (hyperaldosteronism), medications (prednisone, digoxin, and olanzapine), and environmental unfamiliarity during hospitalization. A delirium diagnosis should be based on a high index of suspicion and a careful clinical assessment rather than diagnostic tests.

Table 3

Deconstructing delirium

OUTCOME: Return home

Mr. L’s confusion and delusional jealousy decrease over time, as do his disorientation and inattention, as evidenced by improvement on MMSE scores. His last MMSE score is 27/30, failing mostly in attention and recall.

After sustained improvement in cognition and behavior, Mr. L is discharged home on haloperidol and the remainder of his nonpsychiatric medications with outpatient medical and psychiatric follow-up. Over several months, he continues to show improvement and haloperidol is discontinued.

The authors’ observations

Delirium treatment should focus on prompt identification and management of precipitating and contributing factors.⁷ Antipsychotics are considered first-line treatment for patients with delirium, agitation, or psychosis who pose a risk to themselves or others. Benzodiazepines should be avoided in older patients unless symptoms are secondary to CNS-depressant withdrawal (ie, alcohol, benzodiazepines).⁹

Although there are no-FDA approved medications for delirium, haloperidol has been widely studied and used for treatment of agitation and psychosis in delirium. There is no evidence that low-dose haloperidol is any less effective than olanzapine or risperidone, or is more likely to cause adverse drug effects such as extrapyramidal syndrome.¹⁰ Antipsychotic use in a confused or agitated dementia patient increases risk of mortality compared with dementia patients who do not receive antipsychotics.¹¹ The use of typical or atypical antipsychotics for delirium should be guided by the patient’s characteristics, such as cardiovascular status and presence or absence of underlying dementia. Atypical antipsychotics should be used carefully because—as in Mr. L’s case—anticholinergic side effects of medications such as olanzapine could worsen delirium.⁵ Once delirium has resolved, antipsychotics should be tapered and discontinued.

Other components of delirium treatment and prevention include:

• reorientation (verbally, with clocks, calendars, etc.)
• safe ambulation
• adequate sleep, food, and fluid intake
• adaptive equipment for vision and hearing impairment
• adequate management of pain and other comorbidities.¹²

Related Resources

• Khan RA, Kahn D, Bourgeois JA. Delirium: sifting through the confusion. Curr Psychiatry Rep. 2009;11(3):226-234.
• Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis, and treatment. Crit Care Clin. 2008;24:657-722.
• Young J, Inouye SK. Delirium in older people. BMJ. 2007;334(7598):842-846.

Drug Brand Names

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Atenolol • Tenormin
• Atropine • AtroPen
• Benztropine • Cogentin
• Cimetidine • Tagamet
• Clozapine • Clozaril
• Digoxin • Lanoxicaps, Lanoxin
• Glyburide • DiaBeta, Micronase
• Haloperidol • Haldol
• Levodopa/carbidopa • Parcopa, Sinemet
• Lisinopril • Prinivil, Zestril
• Lorazepam • Ativan
• Meperidine • Demerol
• Mirtazapine • Remeron
• Olanzapine • Zyprexa
• Omeprazole • Prilosec
• Oxybutynin • Ditropan
• Pergolide • Permax
• Phenytoin • Dilantin, Phenytek
• Prednisolone • Orapred, Prelone, others
• Prednisone • Deltasone, Meticorten
• Pyridostigmine • Mestinon
• Ranitidine • Zantac
• Risperidone • Risperdal
• Selegiline • Eldepryl, Zelapar
• Spironolactone • Aldactone
• Tamsulosin • Flomax
• Thioridazine • Mellaril
• Trazodone • Desyrel
• Warfarin • Coumadin

Disclosure

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

CASE: Worsening depression

Mr. N, age 64, is a disabled factory worker with a complicated medical history. He has poorly controlled type II diabetes mellitus; obesity (body mass index 40 kg/m²); complicated cryptogenic cirrhosis with prior esophageal varices, portal gastropathy, splenomegaly, and no encephalopathy; surgically treated colon adenocarcinoma; and bilateral thalamic and right occipital infarcts with residual left homonymous hemianopsia and vertical gaze paresis. Mr. N sustained a perioperative stroke 18 months ago while undergoing a colectomy procedure for colon adenocarcinoma; an MRI done at that time showed the bilateral thalamic and right occipital infarcts. While in the internal medicine consultation clinic, Mr. N expresses suicidal and homicidal thoughts, which prompted the internal medicine team to refer him to the emergency department (ED). The team deems Mr. N’s medical problems stable except for diabetic dyscontrol.

In the ED, Mr. N says he feels sad, worthless, and “tired” of his complex family issues and multiple medical conditions. He says he’s had these feeling for at least a year, but his depression has worsened in the last few days. Mr. N is tearful while explaining his discouragement with following a diet for diabetes; earlier that day he ate an entire chocolate cake. He says all 3 of his children have ongoing substance abuse and relationship problems, but he is particularly focused on his youngest daughter, who is involved with a man who is addicted to drugs and physically abuses her and her children. Mr. N describes a detailed plan to shoot him and then commit suicide. This disclosure prompts the ED physician to admit Mr. N to ensure his safety and stabilize his mood.

Mr. N’s temperature is 36. 4°C (97. 5°F), blood pressure is 123/60 mm Hg, pulse is 81 beats per minute, respiratory rate is 24 breaths per minute, and oxygen saturation is 96% on ambient air. His physical exam is notable only for dysphoria and mild gynecomastia. He shows no evidence of acute cardiopulmonary, gastrointestinal, or other neurologic changes. His serum glucose is 650 mg/dL, and his recent hemoglobin A_1c (HbA_1c) is 10. 9%. His other laboratory tests include a hemoglobin of 11. 7 g/dL; white cell count, 3500/mm³; platelet count, 41, 000/mm³; sodium, 129 mEq/L; potassium, 5. 0 mEq/L; alkaline phosphatase, 90 U/L; aspartate aminotransferase, 23 U/L; alanine aminotransferase, 21 U/L; total bilirubin, 1. 8 mg/dL; creatinine, 1. 2 mg/dL; prothrombin time, 10. 4 sec; and arterial ammonia, <50 ?g/dL. Arterial blood gases are normal.

A year ago, his primary care physician prescribed fluoxetine, 20 mg/d, for fatigue and chronic back pain and neuropathic pain related to diabetes. We continue Mr. N’s outpatient prescription of fluoxetine, 20 mg/d, and low-dose acetaminophen as needed for pain. Furosemide, 40 mg/d, spironolactone, 100 mg/d, and propranolol sustained release, 60 mg/d, are maintained for complications of cirrhosis. Insulin aspart, 22 units with breakfast, 24 units with lunch, and 24 units with supper, also are administered routinely.

We consult with the internal medicine, ophthalmology, neurology, endocrinology, and diabetes services to assist in evaluating and managing Mr. N’s multiple medical conditions.

The authors’ observations

Depression and other forms of psychopathology may be underrecognized in geriatric patients because older adults may not report psychiatric symptoms that are secondary to physical conditions. Cognitive impairment in some older adults also may lead to underreporting of symptoms. Mr. N denies a history of depression, which we confirmed with his wife, daughter, and primary care physician. The late onset of his initial presentation prompted close investigation for a potential medical etiology (Table 1).^1,2

We considered post-stroke depression because shortly after Mr. N’s stroke, his neurologist described emotional lability and frustration related to his poor vision. Depression occurs in one-third of chronic stroke survivors and is prevalent among patients referred for neurologic rehabilitation.¹ Premorbid neuroticism³ and a history of mental illness are predictors of post-stroke depression. Stroke laterality is not related to risk of post-stroke depressive symptoms,³ but women have a higher risk of developing post-stroke depression.³

Table 1

When to consider medical causes of depressive symptoms

Diabetes and depression

Up to 30% of patients with type 2 diabetes mellitus report a lifetime history of major depression.² Depression increases the risk of hyperglycemia and accompanying long-term metabolic complications.^4,5 Few studies have explored the effects of poor glycemic control on depressive symptoms among diabetic patients.^6-9 A literature review revealed no large-scale study investigating worsened depressive symptoms in patients with poor glycemic control.^10,11

The cross-sectional difference between a single episode of major depression and adjustment disorder can be subtle. DSM-IV-TR describes the latter as a maladaptive reaction to an identifiable psychosocial stressor, or stressors, that occurs within 3 months of onset of that stressor (Table 2).¹² Because we did not deem Mr. N’s depressive symptoms, which were evident only when he was hyperglycemic, to be grossly disproportionate to his stressors, we diagnose him with major depression rather than adjustment disorder.

Table 2

DSM-IV-TR diagnostic criteria for adjustment disorder

EVALUATION: No psychiatric history

On admission, Mr. N is overwhelmed, tearful, and dysphoric when describing his situation. He displays no evidence of psychosis, but his judgment and insight are impaired. He shows no change in consciousness or ability to stay awake. Mr. N acknowledges hypersomnolence, anhedonia, anergia, and decreased concentration and continues to express suicidal and homicidal thoughts. He repeatedly denies any personal or family psychiatric history or personal substance abuse, including alcohol and nicotine.

TREATMENT: Glycemic control

Mr. N receives 1 L of saline in the ED and is encouraged to drink more water during hospitalization. With appropriate insulin dosing, Mr. N’s serum glucose levels improve from 650 to 426 mg/dL by the next morning. On his third hospital day, Mr. N’s glucose level is 155 mg/dL in the morning. With tighter glycemic control, his dysphoria improves. He is future-oriented, markedly less dysphoric, and denies homicidal or suicidal ideation. Mr. N is interested in participating in group therapy, and his insight and judgment regarding his homicidal and suicidal thoughts improve. He still doesn’t fully understand the importance of diabetic control, and he struggles with his diet.

On the fourth hospital day, Mr. N’s glucose level rises to 325 mg/dL in the early evening. Subsequently, his mood deteriorates; he becomes increasingly withdrawn and somnolent. With appropriate attention to his dietary intake and supplemental insulin, his serum glucose improves to the 100 to 200 mg/dL range overnight, and his mood improves. When the glucose is controlled, he attends group therapy, tends to his hygiene, denies feeling hopeless, and offers several ideas about how to manage his family situation. After his glucose rises, Mr. N becomes isolative, hopeless, and unable to cope with stressors. With considerable education about the importance of glycemic control, Mr. N is hopeful and future-oriented when he is discharged after 9 days of hospitalization. At outpatient evaluation, he continues to report euthymia with adequate glycemic control.

The authors’ observations

Patients with hyperglycemia may experience symptoms secondary to volume depletion and hyperosmolality. The severity of these symptoms generally is proportional to the extent and duration of the hyperosmolar state. Initially, most patients complain of polyuria and polydipsia, but in more severe cases, mental status changes may evolve and include lethargy, twitching, cloudiness, motor or sensory defects, seizures, and coma. Some evidence shows that hyperglycemic patients with hyperosmolality are symptomatic only if hypernatremia is present.¹³ Mr. N was hyponatremic, which resolved with aggressive hydration and insulin administration.

Traditionally, depression has been observed to worsen glycemic control in diabetic patients; discussion of increased glucose levels leading to worsened depression rarely has been reported. In a meta-analysis, Lustman et al⁷ revealed that depression is significantly associated with hyperglycemia. A review by Li et al¹⁴ demonstrated that depression is much more common in patients with diabetes compared with general population and 45% of diabetes patients with depression were undiagnosed. Calhoun et al¹⁵ showed that for every 1-unit increase in HbA_1c the odds of depressive symptoms increase by 22%. Researchers also found a positive relationship between depression and glycemic control in American Indians.¹⁵

Mr. N’s case is further evidence that the relationship between diabetes and depression is bidirectional and diagnosis and treatment of each illness impacts the other. Although this case does not confirm causality, it highlights the importance of aggressive approaches to screening and treatment of depression in patients with diabetes, and vice versa.

Related Resources

• Katon W, Russo J, Lin EH, et al. Depression and diabetes: factors associated with major depression at five-year follow-up. Psychosomatics. 2009; 50(6): 570-579.
• Biessels GJ, Luchsinger JA. Diabetes and the brain. New York, NY: Humana Press; 2009.

Drug Brand Names

• Fluoxetine • Prozac
• Furosemide • Lasix
• Insulin aspart • NovoLog
• Insulin glargine • Lantus
• Methyldopa • Aldomet
• Propranolol • Inderal
• Reserpine • Serpasil
• Spironolactone • Aldactone

Disclosure

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

CASE: Worsening depression

Mr. N, age 64, is a disabled factory worker with a complicated medical history. He has poorly controlled type II diabetes mellitus; obesity (body mass index 40 kg/m²); complicated cryptogenic cirrhosis with prior esophageal varices, portal gastropathy, splenomegaly, and no encephalopathy; surgically treated colon adenocarcinoma; and bilateral thalamic and right occipital infarcts with residual left homonymous hemianopsia and vertical gaze paresis. Mr. N sustained a perioperative stroke 18 months ago while undergoing a colectomy procedure for colon adenocarcinoma; an MRI done at that time showed the bilateral thalamic and right occipital infarcts. While in the internal medicine consultation clinic, Mr. N expresses suicidal and homicidal thoughts, which prompted the internal medicine team to refer him to the emergency department (ED). The team deems Mr. N’s medical problems stable except for diabetic dyscontrol.

In the ED, Mr. N says he feels sad, worthless, and “tired” of his complex family issues and multiple medical conditions. He says he’s had these feeling for at least a year, but his depression has worsened in the last few days. Mr. N is tearful while explaining his discouragement with following a diet for diabetes; earlier that day he ate an entire chocolate cake. He says all 3 of his children have ongoing substance abuse and relationship problems, but he is particularly focused on his youngest daughter, who is involved with a man who is addicted to drugs and physically abuses her and her children. Mr. N describes a detailed plan to shoot him and then commit suicide. This disclosure prompts the ED physician to admit Mr. N to ensure his safety and stabilize his mood.

Mr. N’s temperature is 36. 4°C (97. 5°F), blood pressure is 123/60 mm Hg, pulse is 81 beats per minute, respiratory rate is 24 breaths per minute, and oxygen saturation is 96% on ambient air. His physical exam is notable only for dysphoria and mild gynecomastia. He shows no evidence of acute cardiopulmonary, gastrointestinal, or other neurologic changes. His serum glucose is 650 mg/dL, and his recent hemoglobin A_1c (HbA_1c) is 10. 9%. His other laboratory tests include a hemoglobin of 11. 7 g/dL; white cell count, 3500/mm³; platelet count, 41, 000/mm³; sodium, 129 mEq/L; potassium, 5. 0 mEq/L; alkaline phosphatase, 90 U/L; aspartate aminotransferase, 23 U/L; alanine aminotransferase, 21 U/L; total bilirubin, 1. 8 mg/dL; creatinine, 1. 2 mg/dL; prothrombin time, 10. 4 sec; and arterial ammonia, <50 ?g/dL. Arterial blood gases are normal.

A year ago, his primary care physician prescribed fluoxetine, 20 mg/d, for fatigue and chronic back pain and neuropathic pain related to diabetes. We continue Mr. N’s outpatient prescription of fluoxetine, 20 mg/d, and low-dose acetaminophen as needed for pain. Furosemide, 40 mg/d, spironolactone, 100 mg/d, and propranolol sustained release, 60 mg/d, are maintained for complications of cirrhosis. Insulin aspart, 22 units with breakfast, 24 units with lunch, and 24 units with supper, also are administered routinely.

We consult with the internal medicine, ophthalmology, neurology, endocrinology, and diabetes services to assist in evaluating and managing Mr. N’s multiple medical conditions.

The authors’ observations

Depression and other forms of psychopathology may be underrecognized in geriatric patients because older adults may not report psychiatric symptoms that are secondary to physical conditions. Cognitive impairment in some older adults also may lead to underreporting of symptoms. Mr. N denies a history of depression, which we confirmed with his wife, daughter, and primary care physician. The late onset of his initial presentation prompted close investigation for a potential medical etiology (Table 1).^1,2

We considered post-stroke depression because shortly after Mr. N’s stroke, his neurologist described emotional lability and frustration related to his poor vision. Depression occurs in one-third of chronic stroke survivors and is prevalent among patients referred for neurologic rehabilitation.¹ Premorbid neuroticism³ and a history of mental illness are predictors of post-stroke depression. Stroke laterality is not related to risk of post-stroke depressive symptoms,³ but women have a higher risk of developing post-stroke depression.³

Table 1

When to consider medical causes of depressive symptoms

Diabetes and depression

Up to 30% of patients with type 2 diabetes mellitus report a lifetime history of major depression.² Depression increases the risk of hyperglycemia and accompanying long-term metabolic complications.^4,5 Few studies have explored the effects of poor glycemic control on depressive symptoms among diabetic patients.^6-9 A literature review revealed no large-scale study investigating worsened depressive symptoms in patients with poor glycemic control.^10,11

The cross-sectional difference between a single episode of major depression and adjustment disorder can be subtle. DSM-IV-TR describes the latter as a maladaptive reaction to an identifiable psychosocial stressor, or stressors, that occurs within 3 months of onset of that stressor (Table 2).¹² Because we did not deem Mr. N’s depressive symptoms, which were evident only when he was hyperglycemic, to be grossly disproportionate to his stressors, we diagnose him with major depression rather than adjustment disorder.

Table 2

DSM-IV-TR diagnostic criteria for adjustment disorder

EVALUATION: No psychiatric history

On admission, Mr. N is overwhelmed, tearful, and dysphoric when describing his situation. He displays no evidence of psychosis, but his judgment and insight are impaired. He shows no change in consciousness or ability to stay awake. Mr. N acknowledges hypersomnolence, anhedonia, anergia, and decreased concentration and continues to express suicidal and homicidal thoughts. He repeatedly denies any personal or family psychiatric history or personal substance abuse, including alcohol and nicotine.

TREATMENT: Glycemic control

Mr. N receives 1 L of saline in the ED and is encouraged to drink more water during hospitalization. With appropriate insulin dosing, Mr. N’s serum glucose levels improve from 650 to 426 mg/dL by the next morning. On his third hospital day, Mr. N’s glucose level is 155 mg/dL in the morning. With tighter glycemic control, his dysphoria improves. He is future-oriented, markedly less dysphoric, and denies homicidal or suicidal ideation. Mr. N is interested in participating in group therapy, and his insight and judgment regarding his homicidal and suicidal thoughts improve. He still doesn’t fully understand the importance of diabetic control, and he struggles with his diet.

On the fourth hospital day, Mr. N’s glucose level rises to 325 mg/dL in the early evening. Subsequently, his mood deteriorates; he becomes increasingly withdrawn and somnolent. With appropriate attention to his dietary intake and supplemental insulin, his serum glucose improves to the 100 to 200 mg/dL range overnight, and his mood improves. When the glucose is controlled, he attends group therapy, tends to his hygiene, denies feeling hopeless, and offers several ideas about how to manage his family situation. After his glucose rises, Mr. N becomes isolative, hopeless, and unable to cope with stressors. With considerable education about the importance of glycemic control, Mr. N is hopeful and future-oriented when he is discharged after 9 days of hospitalization. At outpatient evaluation, he continues to report euthymia with adequate glycemic control.

The authors’ observations

Patients with hyperglycemia may experience symptoms secondary to volume depletion and hyperosmolality. The severity of these symptoms generally is proportional to the extent and duration of the hyperosmolar state. Initially, most patients complain of polyuria and polydipsia, but in more severe cases, mental status changes may evolve and include lethargy, twitching, cloudiness, motor or sensory defects, seizures, and coma. Some evidence shows that hyperglycemic patients with hyperosmolality are symptomatic only if hypernatremia is present.¹³ Mr. N was hyponatremic, which resolved with aggressive hydration and insulin administration.

Traditionally, depression has been observed to worsen glycemic control in diabetic patients; discussion of increased glucose levels leading to worsened depression rarely has been reported. In a meta-analysis, Lustman et al⁷ revealed that depression is significantly associated with hyperglycemia. A review by Li et al¹⁴ demonstrated that depression is much more common in patients with diabetes compared with general population and 45% of diabetes patients with depression were undiagnosed. Calhoun et al¹⁵ showed that for every 1-unit increase in HbA_1c the odds of depressive symptoms increase by 22%. Researchers also found a positive relationship between depression and glycemic control in American Indians.¹⁵

Mr. N’s case is further evidence that the relationship between diabetes and depression is bidirectional and diagnosis and treatment of each illness impacts the other. Although this case does not confirm causality, it highlights the importance of aggressive approaches to screening and treatment of depression in patients with diabetes, and vice versa.

Related Resources

• Katon W, Russo J, Lin EH, et al. Depression and diabetes: factors associated with major depression at five-year follow-up. Psychosomatics. 2009; 50(6): 570-579.
• Biessels GJ, Luchsinger JA. Diabetes and the brain. New York, NY: Humana Press; 2009.

Drug Brand Names

• Fluoxetine • Prozac
• Furosemide • Lasix
• Insulin aspart • NovoLog
• Insulin glargine • Lantus
• Methyldopa • Aldomet
• Propranolol • Inderal
• Reserpine • Serpasil
• Spironolactone • Aldactone

Disclosure

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

CASE: Worsening depression

Mr. N, age 64, is a disabled factory worker with a complicated medical history. He has poorly controlled type II diabetes mellitus; obesity (body mass index 40 kg/m²); complicated cryptogenic cirrhosis with prior esophageal varices, portal gastropathy, splenomegaly, and no encephalopathy; surgically treated colon adenocarcinoma; and bilateral thalamic and right occipital infarcts with residual left homonymous hemianopsia and vertical gaze paresis. Mr. N sustained a perioperative stroke 18 months ago while undergoing a colectomy procedure for colon adenocarcinoma; an MRI done at that time showed the bilateral thalamic and right occipital infarcts. While in the internal medicine consultation clinic, Mr. N expresses suicidal and homicidal thoughts, which prompted the internal medicine team to refer him to the emergency department (ED). The team deems Mr. N’s medical problems stable except for diabetic dyscontrol.

In the ED, Mr. N says he feels sad, worthless, and “tired” of his complex family issues and multiple medical conditions. He says he’s had these feeling for at least a year, but his depression has worsened in the last few days. Mr. N is tearful while explaining his discouragement with following a diet for diabetes; earlier that day he ate an entire chocolate cake. He says all 3 of his children have ongoing substance abuse and relationship problems, but he is particularly focused on his youngest daughter, who is involved with a man who is addicted to drugs and physically abuses her and her children. Mr. N describes a detailed plan to shoot him and then commit suicide. This disclosure prompts the ED physician to admit Mr. N to ensure his safety and stabilize his mood.

Mr. N’s temperature is 36. 4°C (97. 5°F), blood pressure is 123/60 mm Hg, pulse is 81 beats per minute, respiratory rate is 24 breaths per minute, and oxygen saturation is 96% on ambient air. His physical exam is notable only for dysphoria and mild gynecomastia. He shows no evidence of acute cardiopulmonary, gastrointestinal, or other neurologic changes. His serum glucose is 650 mg/dL, and his recent hemoglobin A_1c (HbA_1c) is 10. 9%. His other laboratory tests include a hemoglobin of 11. 7 g/dL; white cell count, 3500/mm³; platelet count, 41, 000/mm³; sodium, 129 mEq/L; potassium, 5. 0 mEq/L; alkaline phosphatase, 90 U/L; aspartate aminotransferase, 23 U/L; alanine aminotransferase, 21 U/L; total bilirubin, 1. 8 mg/dL; creatinine, 1. 2 mg/dL; prothrombin time, 10. 4 sec; and arterial ammonia, <50 ?g/dL. Arterial blood gases are normal.

A year ago, his primary care physician prescribed fluoxetine, 20 mg/d, for fatigue and chronic back pain and neuropathic pain related to diabetes. We continue Mr. N’s outpatient prescription of fluoxetine, 20 mg/d, and low-dose acetaminophen as needed for pain. Furosemide, 40 mg/d, spironolactone, 100 mg/d, and propranolol sustained release, 60 mg/d, are maintained for complications of cirrhosis. Insulin aspart, 22 units with breakfast, 24 units with lunch, and 24 units with supper, also are administered routinely.

We consult with the internal medicine, ophthalmology, neurology, endocrinology, and diabetes services to assist in evaluating and managing Mr. N’s multiple medical conditions.

The authors’ observations

Depression and other forms of psychopathology may be underrecognized in geriatric patients because older adults may not report psychiatric symptoms that are secondary to physical conditions. Cognitive impairment in some older adults also may lead to underreporting of symptoms. Mr. N denies a history of depression, which we confirmed with his wife, daughter, and primary care physician. The late onset of his initial presentation prompted close investigation for a potential medical etiology (Table 1).^1,2

We considered post-stroke depression because shortly after Mr. N’s stroke, his neurologist described emotional lability and frustration related to his poor vision. Depression occurs in one-third of chronic stroke survivors and is prevalent among patients referred for neurologic rehabilitation.¹ Premorbid neuroticism³ and a history of mental illness are predictors of post-stroke depression. Stroke laterality is not related to risk of post-stroke depressive symptoms,³ but women have a higher risk of developing post-stroke depression.³

Table 1

When to consider medical causes of depressive symptoms

Diabetes and depression

Up to 30% of patients with type 2 diabetes mellitus report a lifetime history of major depression.² Depression increases the risk of hyperglycemia and accompanying long-term metabolic complications.^4,5 Few studies have explored the effects of poor glycemic control on depressive symptoms among diabetic patients.^6-9 A literature review revealed no large-scale study investigating worsened depressive symptoms in patients with poor glycemic control.^10,11

The cross-sectional difference between a single episode of major depression and adjustment disorder can be subtle. DSM-IV-TR describes the latter as a maladaptive reaction to an identifiable psychosocial stressor, or stressors, that occurs within 3 months of onset of that stressor (Table 2).¹² Because we did not deem Mr. N’s depressive symptoms, which were evident only when he was hyperglycemic, to be grossly disproportionate to his stressors, we diagnose him with major depression rather than adjustment disorder.

Table 2

DSM-IV-TR diagnostic criteria for adjustment disorder

EVALUATION: No psychiatric history

On admission, Mr. N is overwhelmed, tearful, and dysphoric when describing his situation. He displays no evidence of psychosis, but his judgment and insight are impaired. He shows no change in consciousness or ability to stay awake. Mr. N acknowledges hypersomnolence, anhedonia, anergia, and decreased concentration and continues to express suicidal and homicidal thoughts. He repeatedly denies any personal or family psychiatric history or personal substance abuse, including alcohol and nicotine.

TREATMENT: Glycemic control

Mr. N receives 1 L of saline in the ED and is encouraged to drink more water during hospitalization. With appropriate insulin dosing, Mr. N’s serum glucose levels improve from 650 to 426 mg/dL by the next morning. On his third hospital day, Mr. N’s glucose level is 155 mg/dL in the morning. With tighter glycemic control, his dysphoria improves. He is future-oriented, markedly less dysphoric, and denies homicidal or suicidal ideation. Mr. N is interested in participating in group therapy, and his insight and judgment regarding his homicidal and suicidal thoughts improve. He still doesn’t fully understand the importance of diabetic control, and he struggles with his diet.

On the fourth hospital day, Mr. N’s glucose level rises to 325 mg/dL in the early evening. Subsequently, his mood deteriorates; he becomes increasingly withdrawn and somnolent. With appropriate attention to his dietary intake and supplemental insulin, his serum glucose improves to the 100 to 200 mg/dL range overnight, and his mood improves. When the glucose is controlled, he attends group therapy, tends to his hygiene, denies feeling hopeless, and offers several ideas about how to manage his family situation. After his glucose rises, Mr. N becomes isolative, hopeless, and unable to cope with stressors. With considerable education about the importance of glycemic control, Mr. N is hopeful and future-oriented when he is discharged after 9 days of hospitalization. At outpatient evaluation, he continues to report euthymia with adequate glycemic control.

The authors’ observations

Patients with hyperglycemia may experience symptoms secondary to volume depletion and hyperosmolality. The severity of these symptoms generally is proportional to the extent and duration of the hyperosmolar state. Initially, most patients complain of polyuria and polydipsia, but in more severe cases, mental status changes may evolve and include lethargy, twitching, cloudiness, motor or sensory defects, seizures, and coma. Some evidence shows that hyperglycemic patients with hyperosmolality are symptomatic only if hypernatremia is present.¹³ Mr. N was hyponatremic, which resolved with aggressive hydration and insulin administration.

Traditionally, depression has been observed to worsen glycemic control in diabetic patients; discussion of increased glucose levels leading to worsened depression rarely has been reported. In a meta-analysis, Lustman et al⁷ revealed that depression is significantly associated with hyperglycemia. A review by Li et al¹⁴ demonstrated that depression is much more common in patients with diabetes compared with general population and 45% of diabetes patients with depression were undiagnosed. Calhoun et al¹⁵ showed that for every 1-unit increase in HbA_1c the odds of depressive symptoms increase by 22%. Researchers also found a positive relationship between depression and glycemic control in American Indians.¹⁵

Mr. N’s case is further evidence that the relationship between diabetes and depression is bidirectional and diagnosis and treatment of each illness impacts the other. Although this case does not confirm causality, it highlights the importance of aggressive approaches to screening and treatment of depression in patients with diabetes, and vice versa.

Related Resources

• Katon W, Russo J, Lin EH, et al. Depression and diabetes: factors associated with major depression at five-year follow-up. Psychosomatics. 2009; 50(6): 570-579.
• Biessels GJ, Luchsinger JA. Diabetes and the brain. New York, NY: Humana Press; 2009.

Drug Brand Names

• Fluoxetine • Prozac
• Furosemide • Lasix
• Insulin aspart • NovoLog
• Insulin glargine • Lantus
• Methyldopa • Aldomet
• Propranolol • Inderal
• Reserpine • Serpasil
• Spironolactone • Aldactone

Disclosure

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

CASE: Self-surgery

Dr. T (a pseudonym), a middle-aged male surgeon, arrives in the emergency department (ED) by ambulance after vomiting and losing consciousness at his office. Paramedics place him on an involuntary psychiatric hold, which is permitted in California, after learning that he had been performing surgery on himself.

Dr. T has developed medical complications after attempting to repair his own umbilical hernia. He states that the hernia resulted from weakened periumbilical abdominal muscles after multiple abdominal liposuctions, during which he inserted a cannula through the umbilicus. Dr. T initially repaired the hernia 4 months ago, but the wound margins had dehisced. He had performed the procedure at his ambulatory care surgical suite with help from his surgical assistant. Dr. T says he has performed many procedures on himself, including abdominal and chest liposuction, dermal filler injections, and skin laser resurfacing to improve perceived blemishes and remove hair. These procedures often resulted in poor cosmetic outcomes.

The authors’ observations

Clinical interviews confirmed that Dr. T met DSM-IV-TR criteria for BDD (Table 1).¹ He is excessively preoccupied with perceived physical defects, which cause clinically significant distress, and this preoccupation is not better accounted for by another mental disorder.

Although Dr. T denied any psychotic symptoms during clinical interviews and Mini-Mental State Exam assessment, a reported 77% of BDD patients meet criteria for delusional disorder, somatic type (Table 2).^1,2 Both disorders can be diagnosed concurrently if a patient meets criteria for both disorders.¹ Phillips et al³ have suggested that delusional and non-delusional BDD may constitute the same disorder, spanning a continuum of insight. This hypothesis is supported by reports that selective serotonin reuptake inhibitors (SSRIs) work equally well for both BDD variants.⁴

Table 1

DSM-IV-TR criteria for body dysmorphic disorder

Table 2

DSM-IV-TR criteria for delusional disorder

HISTORY: Accomplishment, anxiety

When we ask Dr. T why he operated on himself, he replies that he did not have time to go to another surgeon. He disagrees when we suggest that he feared that his privacy and professional reputation might be compromised. Dr. T states, “Doctors with walking pneumonia prescribe pills for themselves; this is the same in principle” and “There is no law against operating on oneself.” When we ask if he regrets his actions, he says “I was just overconfident. I did them under local anesthesia and I have a high pain tolerance.” He denies enjoying the pain. He reports that his friends and significant other consider him “courageous” for operating on himself. He denies further plans to perform surgery on himself.

Dr. T has no history of psychiatric hospitalizations or suicide attempts. He has a history of “situational anxiety” and over 3 years his general practitioner prescribed unknown dosages of sertraline, alprazolam, and propranolol, but he did not take these medications regularly and denies taking any other medications. Except for impaired judgment, his mental status exam is within normal limits. He has no other medical problems. He denies alcohol or illicit drug use or a desire to harm himself or others. Dr. T states that as a younger man he was an accomplished athlete and is now an avid body builder who exercises daily and is proud of the intensity and rigor of his workouts.

The authors’ observations

Dr. T does not meet DSM-IV-TR criteria for a current mood or anxiety disorder; however, he has taken medications for what he described as “situational anxiety.” This pattern is consistent with data suggesting that BDD patients feel an unusually high degree of stress in their lives.⁵ Crerand et al⁶ found that >60% of BDD patients had a lifetime history of an anxiety disorder.

Dr. T’s history highlights traits often observed in patients with BDD. As is common in men with BDD, he follows a rigorous exercise regimen.⁷ He also was a competitive athlete, and hypercompetitiveness has significant positive correlation with BDD symptoms.⁸ He is preoccupied with excessive body hair, which is more prevalent in men than in women with BDD.⁹ Dr. T’s work required a keen sense of aesthetics, and it has been observed that individuals with BDD have increased aesthetic sensitivity.^10,11

Although many individuals with BDD struggle socially and financially, some BDD patients are successful and quite accomplished. In a study of 156 Pakistani medical students, 5.8% met criteria for BDD.¹² In The broken mirror,¹³ BDD expert Dr. Katharine Phillips describes caring for many high-functioning health care professionals who suffer from BDD, yet “they provide their patients with superb care … many with this disorder are productive, some are very high achievers.”

EVALUATION: Bad scars

Dr. T has multiple surgical scars on his chest and abdomen (Photo), ecchymoses, and tenderness on palpation. His vital signs are within normal limits and he is otherwise medically healthy. Notable laboratory findings include elevated white blood cell count and platelets, and decreased hemoglobin.

A CT scan shows a large hematoma over the anterior abdominal wall extending toward the flanks with extensive subcutaneous emphysema. The peritoneum is intact. These findings raise the medical team’s concern about possible infection and vascular instability. The involuntary psychiatric hold for observation is continued after evaluation in the ED.

Photo Dr. T’s chest and abdomen during presentation to the ED
Note the asymmetry of the nipples and scarring from prior self-surgeries

The authors’ observations

There is a disconnect between Dr. T’s perception of his physical attributes and the treatment team’s observations. He perceives himself as marred by physical defects, while the treatment team sees him as a handsome and attractive person— excluding his scars from self-surgery.

Patients with BDD frequently are concerned about perceived physical defects that objective observers would consider slight or not noticeable. Three-quarters of individuals with BDD seek surgery or other medical treatment for their perceived physical flaws.⁴ Many patients minimize their BDD symptoms and their distress when talking with health care professionals.¹⁴ Approximately 20% of cosmetic surgery patients report ongoing psychiatric treatment at the time of surgery.¹⁵ Eighty-four percent of cosmetic surgeons state they have refused to operate on a patient because of BDD.¹⁶ However, it may be difficult for surgeons to distinguish a “perfectionist” from a patient with BDD.¹⁷ Even “positive” cosmetic surgery outcomes do not ameliorate BDD symptoms because most patients develop new areas of concern. In a small study of patients with minimal defects who requested cosmetic surgery, surgery did not reduce symptoms of BDD, disability, or psychiatric comorbidity in 6 out of 7 patients at 5-year follow up.¹⁸

Specialized medical equipment, such as surgical instruments and dermabrasion or laser hair removal devices, can be purchased on the Internet, which may increase the likelihood of individuals attempting procedures on themselves. Veale¹⁴ published a retrospective case series of patients who were turned down or unable to afford cosmetic surgery who performed self-surgery. These efforts did not lead to the desired effect, and patients continued to be plagued by their original concerns as well as self-inflicted scarring and damage.

Dr. T had the training and resources to perform cosmetic procedures on himself. Unfortunately, these efforts led to disfigurement. Phillips¹³ states that although self-surgery appears infrequently, it reflects the severe emotional pain and desperation felt by some patients with BDD. Self-surgery is associated with an increased rate of serious suicide attempts.¹⁴ Carefully monitor any BDD patient for suicidal ideation, intent, or plans.

TREATMENT: Refuses follow-up

Dr. T is admitted to the medical service and stabilized with IV fluids and antibiotics. The consultation-liaison service followed him during hospitalization. Because repeated interviews do not uncover grave disability or an imminent danger to himself or others, the involuntary psychiatric hold is discontinued. Dr. T declines psychiatric follow-up care, but says he would consider seeing a mental health professional in the future.

The authors’ observations

This case involves challenging ethical, legal, and countertransference issues. One of the first dilemmas the treatment team encountered was the decision to continue the involuntary hold for observation and assessment. The ED physician and psychiatric resident were faced with telling a fellow physician that he had to remain in the hospital despite his adamant desire to leave. Dr. T’s articulate arguments against staying in the hospital were addressed in order to deliver needed medical treatment. The psychiatric, surgical, and internal medicine teams discussed these countertransference concerns extensively during Dr. T’s hospitalization.

Clearly, Dr. T demonstrated poor judgment by operating on himself, and we aimed to ensure that he received appropriate psychiatric follow-up, but it could not be mandated. After intense and strongly debated ethical and legal discussions with the hospital’s ethicists and risk management team, we determined that we could not file a report with the state medical board because there was no evidence of incompetence, malpractice, or imminent risk to patients. A detailed description of these discussions is omitted from this article to preserve Dr. T’s confidentiality. However, Dr. T will have to disclose and explain the involuntary psychiatric hold on his next medical license renewal.

Our decision was influenced by Phillips,¹³ who found that although patients with BDD may have minimal insight into their illness, “their judgment remains intact in areas unrelated to their body image problem. Attention span and memory are well preserved, and physical and neurologic examinations are normal.” Although Dr. T meets criteria for BDD, mental illness in physicians is not synonymous with impairment.¹⁹

BDD treatment options

With medications and psychotherapy, patients with BDD generally have a good prognosis. A recent meta-analysis found that SSRIs and cognitive-behavioral therapy are effective treatments for BDD.²⁰ In general, higher doses of SSRIs are needed to treat BDD compared with depression. Other medications with evidence of efficacy for BDD include the serotonin norepinephrine reuptake inhibitor venlafaxine²¹ and the anticonvulsant levetiracetam.²² However, clinicians often don’t have the opportunity to try these approaches because BDD patients are difficult to engage in treatment, as is evident in Dr. T’s case. Innovative approaches that combine practical and evidence-based strategies have been manualized.²³ These approaches can help clinicians engage BDD patients in treatment and recognize underlying issues of distorted body image.

Related Resources

• BDD Central. www.bddcentral.com.
• Phillips KA. The broken mirror: understanding and treating body dysmorphic disorder. New York, NY: Oxford University Press; 2005.

Drug Brand Names

• Alprazolam • Xanax
• Levetiracetam • Keppra
• Propranolol • Inderal
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Rapaport receives grant/research support from the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine and is a consultant for Affectis Pharmaceuticals, Methylation Sciences, PAX Pharmaceuticals, and Johnson and Johnson Pharmaceuticals.

Drs. Rafin and Pimstone report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors wish to thank Dr. Kristine Andrade for editorial assistance. We also wish to thank the Institutional Review Board at Cedars-Sinai Medical Center for its review and approval of this case report, and Dr. T for his consent to publish it.

CASE: Self-surgery

Dr. T (a pseudonym), a middle-aged male surgeon, arrives in the emergency department (ED) by ambulance after vomiting and losing consciousness at his office. Paramedics place him on an involuntary psychiatric hold, which is permitted in California, after learning that he had been performing surgery on himself.

Dr. T has developed medical complications after attempting to repair his own umbilical hernia. He states that the hernia resulted from weakened periumbilical abdominal muscles after multiple abdominal liposuctions, during which he inserted a cannula through the umbilicus. Dr. T initially repaired the hernia 4 months ago, but the wound margins had dehisced. He had performed the procedure at his ambulatory care surgical suite with help from his surgical assistant. Dr. T says he has performed many procedures on himself, including abdominal and chest liposuction, dermal filler injections, and skin laser resurfacing to improve perceived blemishes and remove hair. These procedures often resulted in poor cosmetic outcomes.

The authors’ observations

Clinical interviews confirmed that Dr. T met DSM-IV-TR criteria for BDD (Table 1).¹ He is excessively preoccupied with perceived physical defects, which cause clinically significant distress, and this preoccupation is not better accounted for by another mental disorder.

Although Dr. T denied any psychotic symptoms during clinical interviews and Mini-Mental State Exam assessment, a reported 77% of BDD patients meet criteria for delusional disorder, somatic type (Table 2).^1,2 Both disorders can be diagnosed concurrently if a patient meets criteria for both disorders.¹ Phillips et al³ have suggested that delusional and non-delusional BDD may constitute the same disorder, spanning a continuum of insight. This hypothesis is supported by reports that selective serotonin reuptake inhibitors (SSRIs) work equally well for both BDD variants.⁴

Table 1

DSM-IV-TR criteria for body dysmorphic disorder

Table 2

DSM-IV-TR criteria for delusional disorder

HISTORY: Accomplishment, anxiety

When we ask Dr. T why he operated on himself, he replies that he did not have time to go to another surgeon. He disagrees when we suggest that he feared that his privacy and professional reputation might be compromised. Dr. T states, “Doctors with walking pneumonia prescribe pills for themselves; this is the same in principle” and “There is no law against operating on oneself.” When we ask if he regrets his actions, he says “I was just overconfident. I did them under local anesthesia and I have a high pain tolerance.” He denies enjoying the pain. He reports that his friends and significant other consider him “courageous” for operating on himself. He denies further plans to perform surgery on himself.

Dr. T has no history of psychiatric hospitalizations or suicide attempts. He has a history of “situational anxiety” and over 3 years his general practitioner prescribed unknown dosages of sertraline, alprazolam, and propranolol, but he did not take these medications regularly and denies taking any other medications. Except for impaired judgment, his mental status exam is within normal limits. He has no other medical problems. He denies alcohol or illicit drug use or a desire to harm himself or others. Dr. T states that as a younger man he was an accomplished athlete and is now an avid body builder who exercises daily and is proud of the intensity and rigor of his workouts.

The authors’ observations

Dr. T does not meet DSM-IV-TR criteria for a current mood or anxiety disorder; however, he has taken medications for what he described as “situational anxiety.” This pattern is consistent with data suggesting that BDD patients feel an unusually high degree of stress in their lives.⁵ Crerand et al⁶ found that >60% of BDD patients had a lifetime history of an anxiety disorder.

Dr. T’s history highlights traits often observed in patients with BDD. As is common in men with BDD, he follows a rigorous exercise regimen.⁷ He also was a competitive athlete, and hypercompetitiveness has significant positive correlation with BDD symptoms.⁸ He is preoccupied with excessive body hair, which is more prevalent in men than in women with BDD.⁹ Dr. T’s work required a keen sense of aesthetics, and it has been observed that individuals with BDD have increased aesthetic sensitivity.^10,11

Although many individuals with BDD struggle socially and financially, some BDD patients are successful and quite accomplished. In a study of 156 Pakistani medical students, 5.8% met criteria for BDD.¹² In The broken mirror,¹³ BDD expert Dr. Katharine Phillips describes caring for many high-functioning health care professionals who suffer from BDD, yet “they provide their patients with superb care … many with this disorder are productive, some are very high achievers.”

EVALUATION: Bad scars

Dr. T has multiple surgical scars on his chest and abdomen (Photo), ecchymoses, and tenderness on palpation. His vital signs are within normal limits and he is otherwise medically healthy. Notable laboratory findings include elevated white blood cell count and platelets, and decreased hemoglobin.

A CT scan shows a large hematoma over the anterior abdominal wall extending toward the flanks with extensive subcutaneous emphysema. The peritoneum is intact. These findings raise the medical team’s concern about possible infection and vascular instability. The involuntary psychiatric hold for observation is continued after evaluation in the ED.

Photo Dr. T’s chest and abdomen during presentation to the ED
Note the asymmetry of the nipples and scarring from prior self-surgeries

The authors’ observations

There is a disconnect between Dr. T’s perception of his physical attributes and the treatment team’s observations. He perceives himself as marred by physical defects, while the treatment team sees him as a handsome and attractive person— excluding his scars from self-surgery.

Patients with BDD frequently are concerned about perceived physical defects that objective observers would consider slight or not noticeable. Three-quarters of individuals with BDD seek surgery or other medical treatment for their perceived physical flaws.⁴ Many patients minimize their BDD symptoms and their distress when talking with health care professionals.¹⁴ Approximately 20% of cosmetic surgery patients report ongoing psychiatric treatment at the time of surgery.¹⁵ Eighty-four percent of cosmetic surgeons state they have refused to operate on a patient because of BDD.¹⁶ However, it may be difficult for surgeons to distinguish a “perfectionist” from a patient with BDD.¹⁷ Even “positive” cosmetic surgery outcomes do not ameliorate BDD symptoms because most patients develop new areas of concern. In a small study of patients with minimal defects who requested cosmetic surgery, surgery did not reduce symptoms of BDD, disability, or psychiatric comorbidity in 6 out of 7 patients at 5-year follow up.¹⁸

Specialized medical equipment, such as surgical instruments and dermabrasion or laser hair removal devices, can be purchased on the Internet, which may increase the likelihood of individuals attempting procedures on themselves. Veale¹⁴ published a retrospective case series of patients who were turned down or unable to afford cosmetic surgery who performed self-surgery. These efforts did not lead to the desired effect, and patients continued to be plagued by their original concerns as well as self-inflicted scarring and damage.

Dr. T had the training and resources to perform cosmetic procedures on himself. Unfortunately, these efforts led to disfigurement. Phillips¹³ states that although self-surgery appears infrequently, it reflects the severe emotional pain and desperation felt by some patients with BDD. Self-surgery is associated with an increased rate of serious suicide attempts.¹⁴ Carefully monitor any BDD patient for suicidal ideation, intent, or plans.

TREATMENT: Refuses follow-up

Dr. T is admitted to the medical service and stabilized with IV fluids and antibiotics. The consultation-liaison service followed him during hospitalization. Because repeated interviews do not uncover grave disability or an imminent danger to himself or others, the involuntary psychiatric hold is discontinued. Dr. T declines psychiatric follow-up care, but says he would consider seeing a mental health professional in the future.

The authors’ observations

This case involves challenging ethical, legal, and countertransference issues. One of the first dilemmas the treatment team encountered was the decision to continue the involuntary hold for observation and assessment. The ED physician and psychiatric resident were faced with telling a fellow physician that he had to remain in the hospital despite his adamant desire to leave. Dr. T’s articulate arguments against staying in the hospital were addressed in order to deliver needed medical treatment. The psychiatric, surgical, and internal medicine teams discussed these countertransference concerns extensively during Dr. T’s hospitalization.

Clearly, Dr. T demonstrated poor judgment by operating on himself, and we aimed to ensure that he received appropriate psychiatric follow-up, but it could not be mandated. After intense and strongly debated ethical and legal discussions with the hospital’s ethicists and risk management team, we determined that we could not file a report with the state medical board because there was no evidence of incompetence, malpractice, or imminent risk to patients. A detailed description of these discussions is omitted from this article to preserve Dr. T’s confidentiality. However, Dr. T will have to disclose and explain the involuntary psychiatric hold on his next medical license renewal.

Our decision was influenced by Phillips,¹³ who found that although patients with BDD may have minimal insight into their illness, “their judgment remains intact in areas unrelated to their body image problem. Attention span and memory are well preserved, and physical and neurologic examinations are normal.” Although Dr. T meets criteria for BDD, mental illness in physicians is not synonymous with impairment.¹⁹

BDD treatment options

With medications and psychotherapy, patients with BDD generally have a good prognosis. A recent meta-analysis found that SSRIs and cognitive-behavioral therapy are effective treatments for BDD.²⁰ In general, higher doses of SSRIs are needed to treat BDD compared with depression. Other medications with evidence of efficacy for BDD include the serotonin norepinephrine reuptake inhibitor venlafaxine²¹ and the anticonvulsant levetiracetam.²² However, clinicians often don’t have the opportunity to try these approaches because BDD patients are difficult to engage in treatment, as is evident in Dr. T’s case. Innovative approaches that combine practical and evidence-based strategies have been manualized.²³ These approaches can help clinicians engage BDD patients in treatment and recognize underlying issues of distorted body image.

Related Resources

• BDD Central. www.bddcentral.com.
• Phillips KA. The broken mirror: understanding and treating body dysmorphic disorder. New York, NY: Oxford University Press; 2005.

Drug Brand Names

• Alprazolam • Xanax
• Levetiracetam • Keppra
• Propranolol • Inderal
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Rapaport receives grant/research support from the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine and is a consultant for Affectis Pharmaceuticals, Methylation Sciences, PAX Pharmaceuticals, and Johnson and Johnson Pharmaceuticals.

Drs. Rafin and Pimstone report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors wish to thank Dr. Kristine Andrade for editorial assistance. We also wish to thank the Institutional Review Board at Cedars-Sinai Medical Center for its review and approval of this case report, and Dr. T for his consent to publish it.

CASE: Self-surgery

Dr. T (a pseudonym), a middle-aged male surgeon, arrives in the emergency department (ED) by ambulance after vomiting and losing consciousness at his office. Paramedics place him on an involuntary psychiatric hold, which is permitted in California, after learning that he had been performing surgery on himself.

Dr. T has developed medical complications after attempting to repair his own umbilical hernia. He states that the hernia resulted from weakened periumbilical abdominal muscles after multiple abdominal liposuctions, during which he inserted a cannula through the umbilicus. Dr. T initially repaired the hernia 4 months ago, but the wound margins had dehisced. He had performed the procedure at his ambulatory care surgical suite with help from his surgical assistant. Dr. T says he has performed many procedures on himself, including abdominal and chest liposuction, dermal filler injections, and skin laser resurfacing to improve perceived blemishes and remove hair. These procedures often resulted in poor cosmetic outcomes.

The authors’ observations

Clinical interviews confirmed that Dr. T met DSM-IV-TR criteria for BDD (Table 1).¹ He is excessively preoccupied with perceived physical defects, which cause clinically significant distress, and this preoccupation is not better accounted for by another mental disorder.

Although Dr. T denied any psychotic symptoms during clinical interviews and Mini-Mental State Exam assessment, a reported 77% of BDD patients meet criteria for delusional disorder, somatic type (Table 2).^1,2 Both disorders can be diagnosed concurrently if a patient meets criteria for both disorders.¹ Phillips et al³ have suggested that delusional and non-delusional BDD may constitute the same disorder, spanning a continuum of insight. This hypothesis is supported by reports that selective serotonin reuptake inhibitors (SSRIs) work equally well for both BDD variants.⁴

Table 1

DSM-IV-TR criteria for body dysmorphic disorder

Table 2

DSM-IV-TR criteria for delusional disorder

HISTORY: Accomplishment, anxiety

When we ask Dr. T why he operated on himself, he replies that he did not have time to go to another surgeon. He disagrees when we suggest that he feared that his privacy and professional reputation might be compromised. Dr. T states, “Doctors with walking pneumonia prescribe pills for themselves; this is the same in principle” and “There is no law against operating on oneself.” When we ask if he regrets his actions, he says “I was just overconfident. I did them under local anesthesia and I have a high pain tolerance.” He denies enjoying the pain. He reports that his friends and significant other consider him “courageous” for operating on himself. He denies further plans to perform surgery on himself.

Dr. T has no history of psychiatric hospitalizations or suicide attempts. He has a history of “situational anxiety” and over 3 years his general practitioner prescribed unknown dosages of sertraline, alprazolam, and propranolol, but he did not take these medications regularly and denies taking any other medications. Except for impaired judgment, his mental status exam is within normal limits. He has no other medical problems. He denies alcohol or illicit drug use or a desire to harm himself or others. Dr. T states that as a younger man he was an accomplished athlete and is now an avid body builder who exercises daily and is proud of the intensity and rigor of his workouts.

The authors’ observations

Dr. T does not meet DSM-IV-TR criteria for a current mood or anxiety disorder; however, he has taken medications for what he described as “situational anxiety.” This pattern is consistent with data suggesting that BDD patients feel an unusually high degree of stress in their lives.⁵ Crerand et al⁶ found that >60% of BDD patients had a lifetime history of an anxiety disorder.

Dr. T’s history highlights traits often observed in patients with BDD. As is common in men with BDD, he follows a rigorous exercise regimen.⁷ He also was a competitive athlete, and hypercompetitiveness has significant positive correlation with BDD symptoms.⁸ He is preoccupied with excessive body hair, which is more prevalent in men than in women with BDD.⁹ Dr. T’s work required a keen sense of aesthetics, and it has been observed that individuals with BDD have increased aesthetic sensitivity.^10,11

Although many individuals with BDD struggle socially and financially, some BDD patients are successful and quite accomplished. In a study of 156 Pakistani medical students, 5.8% met criteria for BDD.¹² In The broken mirror,¹³ BDD expert Dr. Katharine Phillips describes caring for many high-functioning health care professionals who suffer from BDD, yet “they provide their patients with superb care … many with this disorder are productive, some are very high achievers.”

EVALUATION: Bad scars

Dr. T has multiple surgical scars on his chest and abdomen (Photo), ecchymoses, and tenderness on palpation. His vital signs are within normal limits and he is otherwise medically healthy. Notable laboratory findings include elevated white blood cell count and platelets, and decreased hemoglobin.

A CT scan shows a large hematoma over the anterior abdominal wall extending toward the flanks with extensive subcutaneous emphysema. The peritoneum is intact. These findings raise the medical team’s concern about possible infection and vascular instability. The involuntary psychiatric hold for observation is continued after evaluation in the ED.

Photo Dr. T’s chest and abdomen during presentation to the ED
Note the asymmetry of the nipples and scarring from prior self-surgeries

The authors’ observations

There is a disconnect between Dr. T’s perception of his physical attributes and the treatment team’s observations. He perceives himself as marred by physical defects, while the treatment team sees him as a handsome and attractive person— excluding his scars from self-surgery.

Patients with BDD frequently are concerned about perceived physical defects that objective observers would consider slight or not noticeable. Three-quarters of individuals with BDD seek surgery or other medical treatment for their perceived physical flaws.⁴ Many patients minimize their BDD symptoms and their distress when talking with health care professionals.¹⁴ Approximately 20% of cosmetic surgery patients report ongoing psychiatric treatment at the time of surgery.¹⁵ Eighty-four percent of cosmetic surgeons state they have refused to operate on a patient because of BDD.¹⁶ However, it may be difficult for surgeons to distinguish a “perfectionist” from a patient with BDD.¹⁷ Even “positive” cosmetic surgery outcomes do not ameliorate BDD symptoms because most patients develop new areas of concern. In a small study of patients with minimal defects who requested cosmetic surgery, surgery did not reduce symptoms of BDD, disability, or psychiatric comorbidity in 6 out of 7 patients at 5-year follow up.¹⁸

Specialized medical equipment, such as surgical instruments and dermabrasion or laser hair removal devices, can be purchased on the Internet, which may increase the likelihood of individuals attempting procedures on themselves. Veale¹⁴ published a retrospective case series of patients who were turned down or unable to afford cosmetic surgery who performed self-surgery. These efforts did not lead to the desired effect, and patients continued to be plagued by their original concerns as well as self-inflicted scarring and damage.

Dr. T had the training and resources to perform cosmetic procedures on himself. Unfortunately, these efforts led to disfigurement. Phillips¹³ states that although self-surgery appears infrequently, it reflects the severe emotional pain and desperation felt by some patients with BDD. Self-surgery is associated with an increased rate of serious suicide attempts.¹⁴ Carefully monitor any BDD patient for suicidal ideation, intent, or plans.

TREATMENT: Refuses follow-up

Dr. T is admitted to the medical service and stabilized with IV fluids and antibiotics. The consultation-liaison service followed him during hospitalization. Because repeated interviews do not uncover grave disability or an imminent danger to himself or others, the involuntary psychiatric hold is discontinued. Dr. T declines psychiatric follow-up care, but says he would consider seeing a mental health professional in the future.

The authors’ observations

This case involves challenging ethical, legal, and countertransference issues. One of the first dilemmas the treatment team encountered was the decision to continue the involuntary hold for observation and assessment. The ED physician and psychiatric resident were faced with telling a fellow physician that he had to remain in the hospital despite his adamant desire to leave. Dr. T’s articulate arguments against staying in the hospital were addressed in order to deliver needed medical treatment. The psychiatric, surgical, and internal medicine teams discussed these countertransference concerns extensively during Dr. T’s hospitalization.

Clearly, Dr. T demonstrated poor judgment by operating on himself, and we aimed to ensure that he received appropriate psychiatric follow-up, but it could not be mandated. After intense and strongly debated ethical and legal discussions with the hospital’s ethicists and risk management team, we determined that we could not file a report with the state medical board because there was no evidence of incompetence, malpractice, or imminent risk to patients. A detailed description of these discussions is omitted from this article to preserve Dr. T’s confidentiality. However, Dr. T will have to disclose and explain the involuntary psychiatric hold on his next medical license renewal.

Our decision was influenced by Phillips,¹³ who found that although patients with BDD may have minimal insight into their illness, “their judgment remains intact in areas unrelated to their body image problem. Attention span and memory are well preserved, and physical and neurologic examinations are normal.” Although Dr. T meets criteria for BDD, mental illness in physicians is not synonymous with impairment.¹⁹

BDD treatment options

With medications and psychotherapy, patients with BDD generally have a good prognosis. A recent meta-analysis found that SSRIs and cognitive-behavioral therapy are effective treatments for BDD.²⁰ In general, higher doses of SSRIs are needed to treat BDD compared with depression. Other medications with evidence of efficacy for BDD include the serotonin norepinephrine reuptake inhibitor venlafaxine²¹ and the anticonvulsant levetiracetam.²² However, clinicians often don’t have the opportunity to try these approaches because BDD patients are difficult to engage in treatment, as is evident in Dr. T’s case. Innovative approaches that combine practical and evidence-based strategies have been manualized.²³ These approaches can help clinicians engage BDD patients in treatment and recognize underlying issues of distorted body image.

Related Resources

• BDD Central. www.bddcentral.com.
• Phillips KA. The broken mirror: understanding and treating body dysmorphic disorder. New York, NY: Oxford University Press; 2005.

Drug Brand Names

• Alprazolam • Xanax
• Levetiracetam • Keppra
• Propranolol • Inderal
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Rapaport receives grant/research support from the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine and is a consultant for Affectis Pharmaceuticals, Methylation Sciences, PAX Pharmaceuticals, and Johnson and Johnson Pharmaceuticals.

Drs. Rafin and Pimstone report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors wish to thank Dr. Kristine Andrade for editorial assistance. We also wish to thank the Institutional Review Board at Cedars-Sinai Medical Center for its review and approval of this case report, and Dr. T for his consent to publish it.

CASE: Agitated and violent

Police bring Ms. Y, age 42, to the emergency room (ER) after her boyfriend calls 911 because she is physically aggressive. The police note that the home is in disarray and several windows are broken. Ms. Y is threatening and violent—she bites and spits at her boyfriend and the police. The ER assessment reports that she is “agitated, confused, and not making sense.” She receives IV haloperidol, 5 mg, for agitation and aggressive behavior, but does not improve and receives a second dose of haloperidol approximately 1 hour later.

On examination she is afebrile. Laboratory results are notable for elevated blood urea nitrogen (27 mg/dL) and creatinine (2.3 mg/dL), suggesting renal failure. Her white blood cell (WBC) count is elevated at 14.7 K/μL with increased neutrophil count. Her creatine phosphokinase (CPK) also is elevated at 2,778 U/L. Other lab results, including liver function tests and a rapid plasma reagin, are within normal limits. Urinalysis reveals WBC >50 and leukocyte esterase 3+ WBC/μL. Urine drug screen is negative for barbiturates, benzodiazepines, opiates, and cocaine and her blood alcohol level is <10 mg/dL. She is overweight, but not obese. Ms. Y is admitted to the medical service for workup of rhabdomyolysis and altered mental status.

When the psychiatric consultation-liaison (CL) service evaluates Ms. Y 12 hours after presentation, she is disheveled, drowsy, and lying in bed, with multiple superficial lacerations on her forearms. She is cooperative but claims to have no recollection of the events leading up to her admission. Her speech is soft with a lack of spontaneity, and she demonstrates substantial psychomotor retardation. Her mood is irritable and affect is restricted. She has a latency of thought and difficulty recalling basic historic information. Ms. Y appears confused and frequently responds to questions with “I don’t remember.” She seems frustrated and distressed by her inability to answer questions. She denies suicidal or homicidal ideation and auditory or visual hallucinations, although she appears to be responding to internal stimuli. We cannot complete a Mini-Mental State Exam because she becomes uncooperative. After 10 minutes, Ms. Y ends the interview, stating that too much is being “demanded” of her.

The authors’ observations

Ms. Y’s acute-onset agitation and confusion could be caused by an infection, such as a urinary tract infection, a frequent culprit in delirium or transient psychosis. Seizure activity with postictal confusion also has to be included in the differential, as well as an endogenous psychotic disorder such as schizophrenia or a manic bipolar episode. Ms. Y’s boyfriend of 16 months indicated that Ms. Y uses alcohol but cannot quantify the amount or frequency. We considered and ruled out other intoxicant use as a potential cause of her transient psychosis. An extended drug screen was negative and her lab values did not suggest heavy alcohol use.

HISTORY: Past psychotic episodes

Ms. Y’s boyfriend reports that she had 2 psychiatric hospitalizations approximately 30 years ago, which were precipitated by psychotic symptoms that she developed while abusing drugs. To the best of his knowledge Ms. Y had not used these agents recently. He stated that Ms. Y did not appear to have ongoing psychotic symptoms and had not received psychiatric treatment since she was a teenager until 6 months ago. He describes the current hospitalization as being “just like 6 months ago.”

Medical records reveal that Ms. Y was admitted to our hospital 6 months ago because she was acting violently and combative. She was “talking out of context,” “stated that she was God,” and had auditory hallucinations. She was admitted to the medical service for rhabdomyolysis, which was thought to be caused by hyperactivity or exertion. Ms. Y indicated that she was taking food supplements, including L-carnitine, to help lose weight. Her psychotic symptoms cleared within 24 hours and she was discharged without any psychiatric medications. Her behavioral disturbance was attributed to ingesting excessive amounts of carnitine supplements, and Ms. Y was counseled to abstain from them.

The authors’ observations

Carnitine is a common dietary supplement that is advertised as being safe and effective.¹ It is purported to increase fat oxidation or reduce fat synthesis; however, no trials demonstrate that L-carnitine is effective for weight loss (Box).^2-7 Evidence from well-designed randomized, controlled clinical trials indicates that the safe upper limit of long-term intake is 2,000 mg/d of L-carnitine equivalents.⁸ The data for doses >2,000 mg/d are not sufficient to make a confident conclusion on long-term safety.⁸

Further evaluation for possible causes of Ms. Y’s symptoms include a chest radiography and blood and urine cultures, which are unremarkable. Results of a lumbar puncture are within normal limits. Computed tomography of the head reveals confluent periventricular hypodensities compatible with moderate to severe non-specific white matter disease.

Box

TREATMENT: Rapid improvement

Ms. Y’s renal dysfunction resolves within 24 hours with aggressive hydration and supportive therapy. Her WBC count normalizes and her CPK decreases.

When Ms. Y becomes more cooperative, the CL team pieces together more of her story with further interviews and collateral information from her cousin. Ms. Y’s family history includes an aunt with schizophrenia. Three years ago Ms. Y moved from the Midwest to a large Southern city with her husband, from whom she is divorced. She has 2 children who were removed from her custody when she was a teenager for unclear reasons. At admission, she lives with her boyfriend, whom she plans on marrying.

Ms. Y says she was taking carnitine to improve her energy and lose weight. She recalls that her physicians advised her to discontinue carnitine supplements, but she continued to take “4 or 5 a day” in an ongoing attempt to lose weight. When asked about other supplements, Ms. Y reports regularly consuming 16-ounce energy drinks, including the day before admission. The label on this drink lists L-carnitine and caffeine as main ingredients. She denies regularly drinking other caffeine-containing beverages, including coffee, tea, or soda.

The authors’ observations

Supplements for weight loss may appeal to people’s desire for a “quick fix” that is less demanding than diets and increased physical activity. Supplements are available without a prescription and despite reports of adverse reactions generally are perceived as being safe and having few side effects. These supplements may be marketed as “natural,” which can be misinterpreted as an assurance of safety and efficacy.

Given the similarities of the current admission to the one 6 months ago, we suspect Ms. Y is experiencing transient psychosis secondary to carnitine intoxication. Based on Ms. Y’s boyfriend’s report and the product labeling, we estimate that Ms. Y took approximately 4,000 mg of carnitine in the 24 hours before admission.

Other causes of transient psychosis, such as infectious, metabolic, and neoplastic processes, were considered and ruled out. Seizures with postictal confusion also was ruled out because Ms. Y does not have a history of seizures and there is no evidence of convulsive activity, incontinence, or buccal lacerations. Given Ms. Y’s family history of schizophrenia and reported history of psychotic symptoms as a teenager we considered that she may have an endogenous psychotic disorder. However, her psychotic symptoms were transient, and Ms. Y returned to her baseline level of functioning between episodes.

OUTCOME: Advice to stop

We start Ms. Y on risperidone, 2 mg/d, at bedtime for her psychotic symptoms. Her psychotic symptoms quickly improve. She seems to return to her baseline state approximately 36 hours after admission and is medically cleared for discharge. Risperidone is discontinued after only 1 dose.

Ms. Y is remorseful over her recent aggressive behavior, and fears that her boyfriend will leave her. She denies suicidal and homicidal ideation and does not require inpatient psychiatric hospitalization. We strongly advise her to discontinue carnitine supplements and energy drinks and to limit her caffeine intake. Because Ms. Y’s had continued to use carnitine supplements despite adverse consequences and against medical advice, we refer her for substance abuse treatment.

The authors’ observations

Although temporal coincidence does not necessarily imply causality, in Ms. Y’s case, the relationship between carnitine ingestion and psychiatric symptoms cannot be ignored. Individuals predisposed to mania or psychosis may be more likely to respond adversely after ingesting nutritional supplements or energy drinks.⁹ Ms. Y’s past psychotic episodes suggest that she could be vulnerable to future episodes. She also might have a biologic predisposition to psychosis because of her family history of schizophrenia.

The literature contains at least 1 other reported case of carnitine-induced psychosis. A patient with a history of bipolar disorder presented with auditory hallucinations, persecutory delusions, and verbally threatening and physically assaultive behavior 5 days after beginning nutritional supplements containing carnitine.¹ There also are reports of patients who experienced acute changes in mental status after consuming other nutritional weight loss supplements (Table).^9-17 Chelben et al⁹ describe 3 patients with known psychiatric illness who showed clinical deterioration leading to psychiatric hospitalization after ingesting nutraceutical preparations. This may be a common but unrecognized cause of decompensation in psychiatric patients who take supplements.

This case highlights the importance of being aware of patients’ use of alternative medications or nutritional supplements. Physicians should routinely inquire about the use of weight loss products, energy drinks, and supplements, and patients should be educated about the risks, including potential to exacerbate pre-existing psychiatric disorders.

Table

Psychiatric effects of common weight loss supplements

Related Resources

• National Library of Medicine. Dietary supplements labels database. http://dietarysupplements.nlm.nih.gov/dietary.
• Grossberg G, Fox B. The essential herb-drug-vitamin interaction guide. New York, NY: Broadway Books; 2007.

Drug Brand Names

• Carbamazepine • Tegretol
• Haloperidol • Haldol
• Risperidone • Risperdal
• Valproic acid • Depakene

Disclosure

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

CASE: Agitated and violent

Police bring Ms. Y, age 42, to the emergency room (ER) after her boyfriend calls 911 because she is physically aggressive. The police note that the home is in disarray and several windows are broken. Ms. Y is threatening and violent—she bites and spits at her boyfriend and the police. The ER assessment reports that she is “agitated, confused, and not making sense.” She receives IV haloperidol, 5 mg, for agitation and aggressive behavior, but does not improve and receives a second dose of haloperidol approximately 1 hour later.

On examination she is afebrile. Laboratory results are notable for elevated blood urea nitrogen (27 mg/dL) and creatinine (2.3 mg/dL), suggesting renal failure. Her white blood cell (WBC) count is elevated at 14.7 K/μL with increased neutrophil count. Her creatine phosphokinase (CPK) also is elevated at 2,778 U/L. Other lab results, including liver function tests and a rapid plasma reagin, are within normal limits. Urinalysis reveals WBC >50 and leukocyte esterase 3+ WBC/μL. Urine drug screen is negative for barbiturates, benzodiazepines, opiates, and cocaine and her blood alcohol level is <10 mg/dL. She is overweight, but not obese. Ms. Y is admitted to the medical service for workup of rhabdomyolysis and altered mental status.

When the psychiatric consultation-liaison (CL) service evaluates Ms. Y 12 hours after presentation, she is disheveled, drowsy, and lying in bed, with multiple superficial lacerations on her forearms. She is cooperative but claims to have no recollection of the events leading up to her admission. Her speech is soft with a lack of spontaneity, and she demonstrates substantial psychomotor retardation. Her mood is irritable and affect is restricted. She has a latency of thought and difficulty recalling basic historic information. Ms. Y appears confused and frequently responds to questions with “I don’t remember.” She seems frustrated and distressed by her inability to answer questions. She denies suicidal or homicidal ideation and auditory or visual hallucinations, although she appears to be responding to internal stimuli. We cannot complete a Mini-Mental State Exam because she becomes uncooperative. After 10 minutes, Ms. Y ends the interview, stating that too much is being “demanded” of her.

The authors’ observations

Ms. Y’s acute-onset agitation and confusion could be caused by an infection, such as a urinary tract infection, a frequent culprit in delirium or transient psychosis. Seizure activity with postictal confusion also has to be included in the differential, as well as an endogenous psychotic disorder such as schizophrenia or a manic bipolar episode. Ms. Y’s boyfriend of 16 months indicated that Ms. Y uses alcohol but cannot quantify the amount or frequency. We considered and ruled out other intoxicant use as a potential cause of her transient psychosis. An extended drug screen was negative and her lab values did not suggest heavy alcohol use.

HISTORY: Past psychotic episodes

Ms. Y’s boyfriend reports that she had 2 psychiatric hospitalizations approximately 30 years ago, which were precipitated by psychotic symptoms that she developed while abusing drugs. To the best of his knowledge Ms. Y had not used these agents recently. He stated that Ms. Y did not appear to have ongoing psychotic symptoms and had not received psychiatric treatment since she was a teenager until 6 months ago. He describes the current hospitalization as being “just like 6 months ago.”

Medical records reveal that Ms. Y was admitted to our hospital 6 months ago because she was acting violently and combative. She was “talking out of context,” “stated that she was God,” and had auditory hallucinations. She was admitted to the medical service for rhabdomyolysis, which was thought to be caused by hyperactivity or exertion. Ms. Y indicated that she was taking food supplements, including L-carnitine, to help lose weight. Her psychotic symptoms cleared within 24 hours and she was discharged without any psychiatric medications. Her behavioral disturbance was attributed to ingesting excessive amounts of carnitine supplements, and Ms. Y was counseled to abstain from them.

The authors’ observations

Carnitine is a common dietary supplement that is advertised as being safe and effective.¹ It is purported to increase fat oxidation or reduce fat synthesis; however, no trials demonstrate that L-carnitine is effective for weight loss (Box).^2-7 Evidence from well-designed randomized, controlled clinical trials indicates that the safe upper limit of long-term intake is 2,000 mg/d of L-carnitine equivalents.⁸ The data for doses >2,000 mg/d are not sufficient to make a confident conclusion on long-term safety.⁸

Further evaluation for possible causes of Ms. Y’s symptoms include a chest radiography and blood and urine cultures, which are unremarkable. Results of a lumbar puncture are within normal limits. Computed tomography of the head reveals confluent periventricular hypodensities compatible with moderate to severe non-specific white matter disease.

Box

TREATMENT: Rapid improvement

Ms. Y’s renal dysfunction resolves within 24 hours with aggressive hydration and supportive therapy. Her WBC count normalizes and her CPK decreases.

When Ms. Y becomes more cooperative, the CL team pieces together more of her story with further interviews and collateral information from her cousin. Ms. Y’s family history includes an aunt with schizophrenia. Three years ago Ms. Y moved from the Midwest to a large Southern city with her husband, from whom she is divorced. She has 2 children who were removed from her custody when she was a teenager for unclear reasons. At admission, she lives with her boyfriend, whom she plans on marrying.

Ms. Y says she was taking carnitine to improve her energy and lose weight. She recalls that her physicians advised her to discontinue carnitine supplements, but she continued to take “4 or 5 a day” in an ongoing attempt to lose weight. When asked about other supplements, Ms. Y reports regularly consuming 16-ounce energy drinks, including the day before admission. The label on this drink lists L-carnitine and caffeine as main ingredients. She denies regularly drinking other caffeine-containing beverages, including coffee, tea, or soda.

The authors’ observations

Supplements for weight loss may appeal to people’s desire for a “quick fix” that is less demanding than diets and increased physical activity. Supplements are available without a prescription and despite reports of adverse reactions generally are perceived as being safe and having few side effects. These supplements may be marketed as “natural,” which can be misinterpreted as an assurance of safety and efficacy.

Given the similarities of the current admission to the one 6 months ago, we suspect Ms. Y is experiencing transient psychosis secondary to carnitine intoxication. Based on Ms. Y’s boyfriend’s report and the product labeling, we estimate that Ms. Y took approximately 4,000 mg of carnitine in the 24 hours before admission.

Other causes of transient psychosis, such as infectious, metabolic, and neoplastic processes, were considered and ruled out. Seizures with postictal confusion also was ruled out because Ms. Y does not have a history of seizures and there is no evidence of convulsive activity, incontinence, or buccal lacerations. Given Ms. Y’s family history of schizophrenia and reported history of psychotic symptoms as a teenager we considered that she may have an endogenous psychotic disorder. However, her psychotic symptoms were transient, and Ms. Y returned to her baseline level of functioning between episodes.

OUTCOME: Advice to stop

We start Ms. Y on risperidone, 2 mg/d, at bedtime for her psychotic symptoms. Her psychotic symptoms quickly improve. She seems to return to her baseline state approximately 36 hours after admission and is medically cleared for discharge. Risperidone is discontinued after only 1 dose.

Ms. Y is remorseful over her recent aggressive behavior, and fears that her boyfriend will leave her. She denies suicidal and homicidal ideation and does not require inpatient psychiatric hospitalization. We strongly advise her to discontinue carnitine supplements and energy drinks and to limit her caffeine intake. Because Ms. Y’s had continued to use carnitine supplements despite adverse consequences and against medical advice, we refer her for substance abuse treatment.

The authors’ observations

Although temporal coincidence does not necessarily imply causality, in Ms. Y’s case, the relationship between carnitine ingestion and psychiatric symptoms cannot be ignored. Individuals predisposed to mania or psychosis may be more likely to respond adversely after ingesting nutritional supplements or energy drinks.⁹ Ms. Y’s past psychotic episodes suggest that she could be vulnerable to future episodes. She also might have a biologic predisposition to psychosis because of her family history of schizophrenia.

The literature contains at least 1 other reported case of carnitine-induced psychosis. A patient with a history of bipolar disorder presented with auditory hallucinations, persecutory delusions, and verbally threatening and physically assaultive behavior 5 days after beginning nutritional supplements containing carnitine.¹ There also are reports of patients who experienced acute changes in mental status after consuming other nutritional weight loss supplements (Table).^9-17 Chelben et al⁹ describe 3 patients with known psychiatric illness who showed clinical deterioration leading to psychiatric hospitalization after ingesting nutraceutical preparations. This may be a common but unrecognized cause of decompensation in psychiatric patients who take supplements.

This case highlights the importance of being aware of patients’ use of alternative medications or nutritional supplements. Physicians should routinely inquire about the use of weight loss products, energy drinks, and supplements, and patients should be educated about the risks, including potential to exacerbate pre-existing psychiatric disorders.

Table

Psychiatric effects of common weight loss supplements

Related Resources

• National Library of Medicine. Dietary supplements labels database. http://dietarysupplements.nlm.nih.gov/dietary.
• Grossberg G, Fox B. The essential herb-drug-vitamin interaction guide. New York, NY: Broadway Books; 2007.

Drug Brand Names

• Carbamazepine • Tegretol
• Haloperidol • Haldol
• Risperidone • Risperdal
• Valproic acid • Depakene

Disclosure

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

CASE: Agitated and violent

Police bring Ms. Y, age 42, to the emergency room (ER) after her boyfriend calls 911 because she is physically aggressive. The police note that the home is in disarray and several windows are broken. Ms. Y is threatening and violent—she bites and spits at her boyfriend and the police. The ER assessment reports that she is “agitated, confused, and not making sense.” She receives IV haloperidol, 5 mg, for agitation and aggressive behavior, but does not improve and receives a second dose of haloperidol approximately 1 hour later.

On examination she is afebrile. Laboratory results are notable for elevated blood urea nitrogen (27 mg/dL) and creatinine (2.3 mg/dL), suggesting renal failure. Her white blood cell (WBC) count is elevated at 14.7 K/μL with increased neutrophil count. Her creatine phosphokinase (CPK) also is elevated at 2,778 U/L. Other lab results, including liver function tests and a rapid plasma reagin, are within normal limits. Urinalysis reveals WBC >50 and leukocyte esterase 3+ WBC/μL. Urine drug screen is negative for barbiturates, benzodiazepines, opiates, and cocaine and her blood alcohol level is <10 mg/dL. She is overweight, but not obese. Ms. Y is admitted to the medical service for workup of rhabdomyolysis and altered mental status.

When the psychiatric consultation-liaison (CL) service evaluates Ms. Y 12 hours after presentation, she is disheveled, drowsy, and lying in bed, with multiple superficial lacerations on her forearms. She is cooperative but claims to have no recollection of the events leading up to her admission. Her speech is soft with a lack of spontaneity, and she demonstrates substantial psychomotor retardation. Her mood is irritable and affect is restricted. She has a latency of thought and difficulty recalling basic historic information. Ms. Y appears confused and frequently responds to questions with “I don’t remember.” She seems frustrated and distressed by her inability to answer questions. She denies suicidal or homicidal ideation and auditory or visual hallucinations, although she appears to be responding to internal stimuli. We cannot complete a Mini-Mental State Exam because she becomes uncooperative. After 10 minutes, Ms. Y ends the interview, stating that too much is being “demanded” of her.

The authors’ observations

Ms. Y’s acute-onset agitation and confusion could be caused by an infection, such as a urinary tract infection, a frequent culprit in delirium or transient psychosis. Seizure activity with postictal confusion also has to be included in the differential, as well as an endogenous psychotic disorder such as schizophrenia or a manic bipolar episode. Ms. Y’s boyfriend of 16 months indicated that Ms. Y uses alcohol but cannot quantify the amount or frequency. We considered and ruled out other intoxicant use as a potential cause of her transient psychosis. An extended drug screen was negative and her lab values did not suggest heavy alcohol use.

HISTORY: Past psychotic episodes

Ms. Y’s boyfriend reports that she had 2 psychiatric hospitalizations approximately 30 years ago, which were precipitated by psychotic symptoms that she developed while abusing drugs. To the best of his knowledge Ms. Y had not used these agents recently. He stated that Ms. Y did not appear to have ongoing psychotic symptoms and had not received psychiatric treatment since she was a teenager until 6 months ago. He describes the current hospitalization as being “just like 6 months ago.”

Medical records reveal that Ms. Y was admitted to our hospital 6 months ago because she was acting violently and combative. She was “talking out of context,” “stated that she was God,” and had auditory hallucinations. She was admitted to the medical service for rhabdomyolysis, which was thought to be caused by hyperactivity or exertion. Ms. Y indicated that she was taking food supplements, including L-carnitine, to help lose weight. Her psychotic symptoms cleared within 24 hours and she was discharged without any psychiatric medications. Her behavioral disturbance was attributed to ingesting excessive amounts of carnitine supplements, and Ms. Y was counseled to abstain from them.

The authors’ observations

Carnitine is a common dietary supplement that is advertised as being safe and effective.¹ It is purported to increase fat oxidation or reduce fat synthesis; however, no trials demonstrate that L-carnitine is effective for weight loss (Box).^2-7 Evidence from well-designed randomized, controlled clinical trials indicates that the safe upper limit of long-term intake is 2,000 mg/d of L-carnitine equivalents.⁸ The data for doses >2,000 mg/d are not sufficient to make a confident conclusion on long-term safety.⁸

Further evaluation for possible causes of Ms. Y’s symptoms include a chest radiography and blood and urine cultures, which are unremarkable. Results of a lumbar puncture are within normal limits. Computed tomography of the head reveals confluent periventricular hypodensities compatible with moderate to severe non-specific white matter disease.

Box

TREATMENT: Rapid improvement

Ms. Y’s renal dysfunction resolves within 24 hours with aggressive hydration and supportive therapy. Her WBC count normalizes and her CPK decreases.

When Ms. Y becomes more cooperative, the CL team pieces together more of her story with further interviews and collateral information from her cousin. Ms. Y’s family history includes an aunt with schizophrenia. Three years ago Ms. Y moved from the Midwest to a large Southern city with her husband, from whom she is divorced. She has 2 children who were removed from her custody when she was a teenager for unclear reasons. At admission, she lives with her boyfriend, whom she plans on marrying.

Ms. Y says she was taking carnitine to improve her energy and lose weight. She recalls that her physicians advised her to discontinue carnitine supplements, but she continued to take “4 or 5 a day” in an ongoing attempt to lose weight. When asked about other supplements, Ms. Y reports regularly consuming 16-ounce energy drinks, including the day before admission. The label on this drink lists L-carnitine and caffeine as main ingredients. She denies regularly drinking other caffeine-containing beverages, including coffee, tea, or soda.

The authors’ observations

Supplements for weight loss may appeal to people’s desire for a “quick fix” that is less demanding than diets and increased physical activity. Supplements are available without a prescription and despite reports of adverse reactions generally are perceived as being safe and having few side effects. These supplements may be marketed as “natural,” which can be misinterpreted as an assurance of safety and efficacy.

Given the similarities of the current admission to the one 6 months ago, we suspect Ms. Y is experiencing transient psychosis secondary to carnitine intoxication. Based on Ms. Y’s boyfriend’s report and the product labeling, we estimate that Ms. Y took approximately 4,000 mg of carnitine in the 24 hours before admission.

Other causes of transient psychosis, such as infectious, metabolic, and neoplastic processes, were considered and ruled out. Seizures with postictal confusion also was ruled out because Ms. Y does not have a history of seizures and there is no evidence of convulsive activity, incontinence, or buccal lacerations. Given Ms. Y’s family history of schizophrenia and reported history of psychotic symptoms as a teenager we considered that she may have an endogenous psychotic disorder. However, her psychotic symptoms were transient, and Ms. Y returned to her baseline level of functioning between episodes.

OUTCOME: Advice to stop

We start Ms. Y on risperidone, 2 mg/d, at bedtime for her psychotic symptoms. Her psychotic symptoms quickly improve. She seems to return to her baseline state approximately 36 hours after admission and is medically cleared for discharge. Risperidone is discontinued after only 1 dose.

Ms. Y is remorseful over her recent aggressive behavior, and fears that her boyfriend will leave her. She denies suicidal and homicidal ideation and does not require inpatient psychiatric hospitalization. We strongly advise her to discontinue carnitine supplements and energy drinks and to limit her caffeine intake. Because Ms. Y’s had continued to use carnitine supplements despite adverse consequences and against medical advice, we refer her for substance abuse treatment.

The authors’ observations

Although temporal coincidence does not necessarily imply causality, in Ms. Y’s case, the relationship between carnitine ingestion and psychiatric symptoms cannot be ignored. Individuals predisposed to mania or psychosis may be more likely to respond adversely after ingesting nutritional supplements or energy drinks.⁹ Ms. Y’s past psychotic episodes suggest that she could be vulnerable to future episodes. She also might have a biologic predisposition to psychosis because of her family history of schizophrenia.

The literature contains at least 1 other reported case of carnitine-induced psychosis. A patient with a history of bipolar disorder presented with auditory hallucinations, persecutory delusions, and verbally threatening and physically assaultive behavior 5 days after beginning nutritional supplements containing carnitine.¹ There also are reports of patients who experienced acute changes in mental status after consuming other nutritional weight loss supplements (Table).^9-17 Chelben et al⁹ describe 3 patients with known psychiatric illness who showed clinical deterioration leading to psychiatric hospitalization after ingesting nutraceutical preparations. This may be a common but unrecognized cause of decompensation in psychiatric patients who take supplements.

This case highlights the importance of being aware of patients’ use of alternative medications or nutritional supplements. Physicians should routinely inquire about the use of weight loss products, energy drinks, and supplements, and patients should be educated about the risks, including potential to exacerbate pre-existing psychiatric disorders.

Table

Psychiatric effects of common weight loss supplements

Related Resources

• National Library of Medicine. Dietary supplements labels database. http://dietarysupplements.nlm.nih.gov/dietary.
• Grossberg G, Fox B. The essential herb-drug-vitamin interaction guide. New York, NY: Broadway Books; 2007.

Drug Brand Names

• Carbamazepine • Tegretol
• Haloperidol • Haldol
• Risperidone • Risperdal
• Valproic acid • Depakene

Disclosure

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

CASE: Nude and mute

Mr. M, age 45, is found naked outside his apartment. He has a history of schizophrenia, paranoid type, hypertension, and diet-controlled type 2 diabetes mellitus. His schizophrenia has been treated with ziprasidone, 160 mg/d, but 2 months ago he stopped taking his medication and seeing his psychiatrist. He does not respond to questions from police and is taken to a local emergency department for medical workup of altered mental status.

Mr. M is noted to have bilateral conjunctival discharge and a white blood cell (WBC) count of 15,000/mm³. Vital signs, physical examination, laboratory studies, and head CT are otherwise within normal limits. Mr. M is medically cleared for his 15^th admission to our inpatient psychiatric facility in the last 7 years. He is divorced, has 2 adult sons, and receives Social Security disability benefits.

Mr. M is alert but guarded and mute and appears to be internally preoccupied. His mood is euthymic and his facial expressions do not vary much and are similar to a blank stare. His grooming and hygiene are poor, but there is no evidence of delusions or suicidal or homicidal ideation. He paces around the unit or sits in his bed staring straight ahead, occasionally mouthing inaudible words but remaining nonverbal.

Mr. M is restarted on his previous dose of ziprasidone and referred to the primary care physician in our inpatient psychiatric facility for further evaluation. His admission vitals and laboratory values show a platelet count of 124,000/mm³, glucose of 113 mg/dL, triglycerides of 160 mg/dL, high-density lipoprotein of 37 mg/dL, and hemoglobin A_1c of 6%. Mr. M needs help drinking fluids but resists solid foods as well as medications, including lorazepam, 3 mg/d, and most scheduled doses of ziprasidone. On day 3, Mr. M’s extremities are rigid and he has poor oral intake. We diagnose Mr. M with catatonia based on his immobility, negativity, and mutism.

The authors’ observations

The literature describes >40 signs of catatonia.^1-11 According to DSM-IV-TR, catatonia may occur in the context of schizophrenia, a mood disorder, or a general medical condition. DSM-IV-TR criteria for catatonia include:

• motor immobility as evidenced by catalepsy or stupor
• excessive motor activity
• extreme negativism or mutism
• peculiarities of voluntary movements as evidenced by posturing, stereotypic movements, or grimacing
• echolalia or echopraxia.¹²

Only 2 signs are necessary to meet the diagnostic criteria for catatonia.^11,12 Several catatonia rating scales—including the Bush-Francis Catatonia Rating Scale (BFCRS)—have been found to be highly reliable for screening for and rating the severity of catatonia. Such tools also can be used serially to monitor treatment efficacy. The BFCRS takes 5 minutes to administer; the screen is considered positive if ≥2 of the first 14 items on the scale are present.¹³ Mr. M exhibits immobility and mutism, which are the most common signs of catatonia.

In patients with catatonia, poor oral intake may result in malnutrition that often requires parenteral nutrition or intravenous fluids^1,10 and dehydration that may lead to dental caries, gum disease, constipation, and ileus.¹ Pneumonia may occur secondary to atelectasis or buildup of respiratory secretions and possibly aspiration.⁷ Vaginal infections may develop secondary to poor hygiene.¹ Immobility and malnutrition may lead to infection and decubitus ulcers.¹ Finally, immobility also may cause urinary incontinence,^2,10 nerve palsies, flexion contractions, and rhabdomyolysis.¹

EVALUATION: Venous complications

On day 3, Mr. M is referred to a local emergency department, where he is assessed for delirium and dehydration because of increased WBC count and diaphoresis. The medical staff finds bilateral pulmonary embolisms and a deep vein thrombosis (DVT) of his left lower leg.

The authors’ observations

Catatonia is associated with an increased risk of venous thromboembolism because of the increased risk of venous stasis and hypercoagulability, both elements of Virchow’s triad for thrombogenesis.^1-10,14,15 The third element of Virchow’s triad, vascular injury, does not appear to directly increase the risk for thromboembolic events in catatonic states.

Catatonia-specific causes for venous stasis include immobility, prolonged use of physical restraints, and sedation as a side effect of antipsychotic use.¹⁶

Causes for hypercoagulability during catatonic states include:

• increased catecholamine levels during excited states³
• hyperhomocysteinemia secondary to poor diet, smoking, and/or high caffeine consumption¹⁶
• increased anticardiolipin and/or anti-phospholipid antibody levels secondary to use of specific antipsychotics, such as chlorpromazine and clozapine¹⁶
• increased platelet aggregation secondary to hyperprolactinemia caused by low-potency conventional antipsychotics, such as chlorpromazine^16,17
• increased platelet activation caused by altered levels of platelet serotonin in depressed patients.¹⁸

Patients taking low-potency conventional antipsychotics may have a 7-fold greater risk for thromboembolic events compared with those who do not use these medications.¹⁶

Reducing thromboembolic risk

Diagnose catatonia early. Treating symptoms of catatonia early with benzodiazepines (and, in refractory cases, with electroconvulsive therapy) prevents immobility, thereby decreasing the risk of thromboembolic events.^3,11 It may be useful to minimize antipsychotic use.

Monitor activity levels. Fatal thromboembolic events may appear early in the course of catatonia before risk factors associated with thromboembolic events are evident.⁴ However, these events may be more common when the patient resumes movement.³ Monitor patients’ activity status and encourage ambulation throughout treatment.

Monitor vital signs for signs of pulmonary embolism, including hypoxia, tachycardia, tachypnea, and fever. Take serial pulse oximetry and, if indicated, arterial blood gas measurements to monitor hemoglobin oxygen saturation. Be vigilant for other signs and symptoms of pulmonary embolism and DVT (Table).

Consider prophylactic treatment. Some studies recommend prophylaxis against thromboembolic events in catatonic patients.^3-6,10,15 These measures include:

• intravenous fluids
• nasogastric tube feeding
• physical examinations to assess for signs of DVT
• support stockings
• sequential/pneumatic compression devices
• physical therapy or range-of-motion exercises
• complete anticoagulation during immobility, although there are no data that support using anticoagulation medications in catatonic patients who have not yet experienced a thromboembolic event.

Consider prophylactic antithrombotic treatment in catatonic patients and other immobile inpatients who have risk factors for thromboembolic events.^9,16 Although it has not been rigorously tested, the Algorithm suggested by Malý et al¹⁵ can serve as a guideline for determining the need for prophylaxis against venous thromboembolism in psychiatric inpatient settings.

Table

Signs and symptoms of deep vein thrombosis and pulmonary embolism

Algorithm

Does my patient need venous thromboembolism prophylaxis?

OUTCOME: Stable and speaking

In the hospital, Mr. M remains immobile and mute for several days. The hospital’s psychiatric consult team recommends lorazepam, 3 mg/d, to address his catatonia. Mr. M improves and begins speaking and eating after starting lorazepam, but becomes agitated, banging his head against walls and threatening to jump out the window. Because this puts him at risk for trauma, Mr. M is not a good candidate for warfarin therapy, and an inferior vena cava filter is placed on an emergency basis. Later, a Dobhoff tube is placed for feeding and administering oral medications.

Mr. M’s catatonic state gradually improves and he begins to respond to the staff with short phrases, eats all of his food, and accepts oral medications. He is transferred back to our inpatient psychiatric facility with haloperidol, 10 mg/d, lorazepam, 3 mg/d, and benztro-pine, 2 mg/d, in addition to sulfacetamide eye drops for bilateral conjunctivitis. At our facility, we start him on warfarin, 5 mg/d, and closely monitor his international normalized ratio levels, with a plan to remove the inferior vena cava filter after 6 months of anticoagulation therapy. Mr. M remains at our facility for 3 weeks to stabilize his medications and is discharged to his apartment.

Six months after being discharged from our facility, Mr. M is stable at an intensive outpatient mental health program.

Related Resources

• Fink M, Taylor MA. Catatonia: a clinician’s guide to diagnosis and treatment. Cambridge, United Kingdom: Cambridge University Press; 2003.
• Snow V, Qaseem A, Barry P, et al, and American College of Physicians; American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146(3):204-210.

Drug Brand Names

• Benztropine • Cogentin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Haloperidol • Haldol
• Lorazepam • Ativan
• Sulfacetamide • Sulamyd
• Warfarin • Coumadin
• Ziprasidone • Geodon

Disclosure

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

CASE: Nude and mute

Mr. M, age 45, is found naked outside his apartment. He has a history of schizophrenia, paranoid type, hypertension, and diet-controlled type 2 diabetes mellitus. His schizophrenia has been treated with ziprasidone, 160 mg/d, but 2 months ago he stopped taking his medication and seeing his psychiatrist. He does not respond to questions from police and is taken to a local emergency department for medical workup of altered mental status.

Mr. M is noted to have bilateral conjunctival discharge and a white blood cell (WBC) count of 15,000/mm³. Vital signs, physical examination, laboratory studies, and head CT are otherwise within normal limits. Mr. M is medically cleared for his 15^th admission to our inpatient psychiatric facility in the last 7 years. He is divorced, has 2 adult sons, and receives Social Security disability benefits.

Mr. M is alert but guarded and mute and appears to be internally preoccupied. His mood is euthymic and his facial expressions do not vary much and are similar to a blank stare. His grooming and hygiene are poor, but there is no evidence of delusions or suicidal or homicidal ideation. He paces around the unit or sits in his bed staring straight ahead, occasionally mouthing inaudible words but remaining nonverbal.

Mr. M is restarted on his previous dose of ziprasidone and referred to the primary care physician in our inpatient psychiatric facility for further evaluation. His admission vitals and laboratory values show a platelet count of 124,000/mm³, glucose of 113 mg/dL, triglycerides of 160 mg/dL, high-density lipoprotein of 37 mg/dL, and hemoglobin A_1c of 6%. Mr. M needs help drinking fluids but resists solid foods as well as medications, including lorazepam, 3 mg/d, and most scheduled doses of ziprasidone. On day 3, Mr. M’s extremities are rigid and he has poor oral intake. We diagnose Mr. M with catatonia based on his immobility, negativity, and mutism.

The authors’ observations

The literature describes >40 signs of catatonia.^1-11 According to DSM-IV-TR, catatonia may occur in the context of schizophrenia, a mood disorder, or a general medical condition. DSM-IV-TR criteria for catatonia include:

• motor immobility as evidenced by catalepsy or stupor
• excessive motor activity
• extreme negativism or mutism
• peculiarities of voluntary movements as evidenced by posturing, stereotypic movements, or grimacing
• echolalia or echopraxia.¹²

Only 2 signs are necessary to meet the diagnostic criteria for catatonia.^11,12 Several catatonia rating scales—including the Bush-Francis Catatonia Rating Scale (BFCRS)—have been found to be highly reliable for screening for and rating the severity of catatonia. Such tools also can be used serially to monitor treatment efficacy. The BFCRS takes 5 minutes to administer; the screen is considered positive if ≥2 of the first 14 items on the scale are present.¹³ Mr. M exhibits immobility and mutism, which are the most common signs of catatonia.

In patients with catatonia, poor oral intake may result in malnutrition that often requires parenteral nutrition or intravenous fluids^1,10 and dehydration that may lead to dental caries, gum disease, constipation, and ileus.¹ Pneumonia may occur secondary to atelectasis or buildup of respiratory secretions and possibly aspiration.⁷ Vaginal infections may develop secondary to poor hygiene.¹ Immobility and malnutrition may lead to infection and decubitus ulcers.¹ Finally, immobility also may cause urinary incontinence,^2,10 nerve palsies, flexion contractions, and rhabdomyolysis.¹

EVALUATION: Venous complications

On day 3, Mr. M is referred to a local emergency department, where he is assessed for delirium and dehydration because of increased WBC count and diaphoresis. The medical staff finds bilateral pulmonary embolisms and a deep vein thrombosis (DVT) of his left lower leg.

The authors’ observations

Catatonia is associated with an increased risk of venous thromboembolism because of the increased risk of venous stasis and hypercoagulability, both elements of Virchow’s triad for thrombogenesis.^1-10,14,15 The third element of Virchow’s triad, vascular injury, does not appear to directly increase the risk for thromboembolic events in catatonic states.

Catatonia-specific causes for venous stasis include immobility, prolonged use of physical restraints, and sedation as a side effect of antipsychotic use.¹⁶

Causes for hypercoagulability during catatonic states include:

• increased catecholamine levels during excited states³
• hyperhomocysteinemia secondary to poor diet, smoking, and/or high caffeine consumption¹⁶
• increased anticardiolipin and/or anti-phospholipid antibody levels secondary to use of specific antipsychotics, such as chlorpromazine and clozapine¹⁶
• increased platelet aggregation secondary to hyperprolactinemia caused by low-potency conventional antipsychotics, such as chlorpromazine^16,17
• increased platelet activation caused by altered levels of platelet serotonin in depressed patients.¹⁸

Patients taking low-potency conventional antipsychotics may have a 7-fold greater risk for thromboembolic events compared with those who do not use these medications.¹⁶

Reducing thromboembolic risk

Diagnose catatonia early. Treating symptoms of catatonia early with benzodiazepines (and, in refractory cases, with electroconvulsive therapy) prevents immobility, thereby decreasing the risk of thromboembolic events.^3,11 It may be useful to minimize antipsychotic use.

Monitor activity levels. Fatal thromboembolic events may appear early in the course of catatonia before risk factors associated with thromboembolic events are evident.⁴ However, these events may be more common when the patient resumes movement.³ Monitor patients’ activity status and encourage ambulation throughout treatment.

Monitor vital signs for signs of pulmonary embolism, including hypoxia, tachycardia, tachypnea, and fever. Take serial pulse oximetry and, if indicated, arterial blood gas measurements to monitor hemoglobin oxygen saturation. Be vigilant for other signs and symptoms of pulmonary embolism and DVT (Table).

Consider prophylactic treatment. Some studies recommend prophylaxis against thromboembolic events in catatonic patients.^3-6,10,15 These measures include:

• intravenous fluids
• nasogastric tube feeding
• physical examinations to assess for signs of DVT
• support stockings
• sequential/pneumatic compression devices
• physical therapy or range-of-motion exercises
• complete anticoagulation during immobility, although there are no data that support using anticoagulation medications in catatonic patients who have not yet experienced a thromboembolic event.

Consider prophylactic antithrombotic treatment in catatonic patients and other immobile inpatients who have risk factors for thromboembolic events.^9,16 Although it has not been rigorously tested, the Algorithm suggested by Malý et al¹⁵ can serve as a guideline for determining the need for prophylaxis against venous thromboembolism in psychiatric inpatient settings.