Sudden death in patients receiving clozapine treatment: A preliminary investigation

The risk of sudden death during clozapine treatment is controversial. The authors present a review of sudden deaths that occurred at Sha'ar Menashe Mental Health Center between January 1991 and August 1997. The number of cases of deceased inpatients was retrieved from the hospital's computerized database and divided into three groups: sudden death, suicide, and disease-related death. Copies of mandatory reports of sudden death filed with the Ministry of Health were obtained, and the corresponding patient records were reviewed. The rates of sudden death, suicide, and disease-related deaths were calculated for clozapine-treated patients (CTPs) during and after treatment and for patients treated with other psychiatric agents (non-CTPs). Among 561 CTPs, there were 4 sudden deaths during treatment, 2 sudden deaths after treatment, 2 suicides during treatment, and 2 disease-related deaths during treatment. Among 4918 non-CTPs, there were 14 sudden deaths, 5 suicides, and 86 disease-related deaths, all of which occurred during treatment with other psychiatric agents. CTPs who experienced sudden death were 10.37 years younger and healthier than non-CTPs who experienced sudden death. The sudden death rate was 3.8 times higher for CTPs than for non-CTPs, whereas the rate of disease-related death was 5 times higher for non-CTPs than for CTPs. Contrary to expectations, the rate of suicide among patients currently receiving clozapine in this sample was 3.6 times higher than among non-CTPs. Because CTPs who experienced sudden death were also younger and healthier, it seems that treatment with clozapine may present a greater risk for sudden death than treatment with other psychiatric medications. The limited number of sudden death cases and deaths from other causes should be noted so that these findings are considered with caution.