Clozapine and Postmortem Redistribution

Ms. A, a 22-year-old obese African American woman, was hospitalized for treatment of schizoaffective disorder, impulse control disorder, mild mental retardation, and borderline personality disorder. Because of previous treatment problems, she was given clozapine. It was titrated to 350 mg/day over the next month; improvement was noted. Ms. A’s other medications included haloperidol, gabapentin, ranitidine, benztropine, birth control pills, and docusate sodium. Ms. A displayed no signs of toxicity nor did she complain of side effects. About 6 weeks after starting clozapine, Ms. A was found unresponsive. Resuscitation attempts were unsuccessful. An autopsy performed approximately 8 hours later revealed no clozapine in her stomach (consistent with reports of medication refusal for 24 hours before her death and her history of noncompliance) and a clozapine level obtained from cardiac blood of 4500 ng/ml (a level greater than 1300 ng/ml is considered toxic). The coroner expressed concern over the possibility of suicide. On the basis of our review of the case, suicide seems very unlikely. There were no overt signs of toxicity, and staff reported no change in behavior.