Clozapine and Pulmonary Embolus

Mr. A, a 29-year-old man (6 feet tall, 180 lb) with a longstanding history of schizoaffective disorder and panic disorder with agoraphobia, was treated with a combination of 20 mg/day of olanzapine and 225 mg/day of extended-release venlafaxine as well as clonazepam, 1 mg/day as needed. During a hospitalization for a recurrence of mixed manic and psychotic symptoms and severe self-mutilation, his olanzapine treatment was discontinued. Since he had only partially responded to both risperidone and olanzapine, clozapine treatment was initiated. The other psychotropic medications were continued. Standard titration was used, and his pulse rate was assessed.

After 6 weeks Mr. A had reached a dose of 300 mg/day and had had a good clinical response to clozapine. He then complained of chest pain and was noted to have symptomatic supraventricular tachycardia, which disappeared after cardioversion. He was admitted to a medical unit and hooked up to telemetry equipment. Six hours later he was found collapsed on the floor and failed to respond to resuscitation. An autopsy revealed a large pulmonary saddle embolus. Mr. A had no family history suggestive of a familial coagulopathy or cardiovascular illness except for an aunt who died of sudden cardiac arrest in her 30s. He exercised moderately, was not obese, did not smoke, and had not had surgery recently. He had had a previous episode of supraventricular tachycardia while taking olanzapine, which disappeared spontaneously.