Residents' Voices

Constipation: A potentially serious adverse effect of clozapine that’s often overlooked

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Clozapine is the most effective second-generation antipsychotic for the treatment of refractory schizophrenia. It can reduce delusions and hallucinations in patients who are unresponsive to other antipsychotic medications. Further, clozapine is the only agent known to reduce suicidal urges.1

Unfortunately, clozapine is associated with numerous adverse effects, most notably agranulocytosis, a rare but potentially fatal adverse effect that occurs in approximately 1% to 2% of patients during the first year of treatment.2 Other adverse effects associated with clozapine are weight gain, sedation, orthostatic hypotension, sialorrhea, constipation, hyperglycemia, hyperlipidemia, myocarditis, and seizures. Among these adverse effects, constipation, which can progress to life-threatening gastrointestinal (GI) hypomotility and ileus, is often overlooked. Up to 60% of patients who are administered clozapine experience constipation.3 A recent review found that potentially life-threatening clozapine-induced ileus occurred in approximately 3 per 1,000 patients, and 28 deaths have been documented.4

In this case report, I describe a patient who received clozapine and experienced constipation that led to an intestinal obstruction. I discuss the importance of prompt diagnosis and treatment approaches to prevent severe constipation in patients who are prescribed clozapine.

CASE REPORT

Mr. L, age 24, has schizophrenia, depression, mild intellectual disability, and congenital human immunodeficiency virus (HIV). He has had multiple unsuccessful antipsychotic trials but is compliant with highly active antiretroviral therapy for HIV. After experiencing worsening aggressive behavior for a third time, Mr. L was involuntarily committed to our Crises Response Center.

Mr. L was admitted to the acute inpatient psychiatry unit. He reported having auditory hallucinations, which included whispering sounds with intermittent music, mostly at night. He also reported decreased sleep, poor appetite, and low energy, but denied feelings of depression or mania.

During the mental status examination, Mr. L was calm and cooperative, but easily distracted. He said he smoked cigarettes but denied any current alcohol or illicit drug use. Mr. L’s urine drug screen was negative.

External medication records showed Mr. L had been prescribed haloperidol, risperidone, chlorpromazine, olanzapine, aripiprazole, quetiapine, bupropion, sodium valproate, and topiramate, for the treatment of schizophrenia, with no significant improvement.

Continue to: On hospital Day 3, Mr. L...

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