Potentially fatal outcomes associated with clozapine

Abstract

Clozapine has been shown to be the most efficacious therapy for treatment resistant schizophrenia, estimated at one third of all schizophrenia cases. There is significant morbidity and mortality associated with clozapine including risk of agranulocytosis, aspiration pneumonia, bowel ischemia, myocarditis, seizures, and weight gain. Here we present a case of a 62-year-old man with chronic paranoid schizophrenia refractory to numerous antipsychotics who was started on clozapine therapy during an acute inpatient psychiatric admission. Within three weeks of starting clozapine, the patient developed flu-like symptoms, pleuritic chest pain, and was sent to a medical hospital for evaluation. After transfer, the patient had a rapidly deteriorating course with newly developed congestive heart failure, acute respiratory failure requiring intubation, and cardiovascular collapse requiring vasopressors. The patient expired within two days of transfer and four days after initial symptoms developed. The underlying etiology in this case is likely clozapine induced myocarditis leading to rapid cardiovascular collapse and death. Mortality with clozapine induced myocarditis has been estimated up to 24%. Given that 90% of clozapine cardiotoxic sequelae are seen in the first month post-initiation, more rigorous post-initiation surveillance is recommended for the first four weeks of clozapine with weekly cardiac enzymes (troponins, creatinine kinase-MB), EKG, and acute inflammatory markers (C-reactive protein, and erythrocyte sedimentation rate).