Sudden cardiac death with clozapine and sertraline combination

OBJECTIVE: To report a case of sudden cardiac death in a patient receiving combination therapy with clozapine and sertraline. CASE SUMMARY: A 26-year-old white man was discovered dead at his residence. His medical history included chronic paranoid schizophrenia, obsessive-com pulsive disorder, major depressive disorder, obstructive sleep apnea, and a kathisia, He had no prior history of cardiovascular disease. His medication regimen included clozapine 100 mg twice daily (started 4 y prior to his de ath), risperidone 3 mg twice daily, sertraline 200 mg once daily, atenolol 50 mg twice daily, and lorazepam 0.5 mg four times daily. Autopsy and toxic ology studies revealed cardiomegaly suggestive of idiopathic cardiomyopathy , single-vessel coronary artery disease, sertraline and clozapine blood con centrations in the expected range, undetectable lorazepam and risperidone b lood concentrations, obesity, and moderate fatty changes to the liver. The most likely cause of death was sudden cardiac death due to acute cardiac ar rhythmia. DISCUSSION: Clozapine is structurally similar to the tricyclic antidepressa nts, which have type 1A antiarrhythmic properties. Case reports have descri bed electrocardiographic abnormalities, cardiomyopathy, and fatal myocardit is associated with its use. Unexplained bath in patients on clozapine thera py has also been reported. Sertraline appears to have less cardiac effect; however, one report as observed clinically significant QT prolongation duri ng sertraline therapy. CONCLUSIONS: Clozapine-induced cardiomyopathy and cardiac arrhythmia from c lozapine and/or sertraline use may have contributed to this man's death.