Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: Results of a 10-year naturalistic study

Objective: The goal of this 10-year naturalistic study was to examine, in clozapine-treated patients, the change in cardiovascular risk factors following clozapine initiation and the mortality estimates from cardiovascular disease. Method: Data were collected from medical records from January 1992 to December 2003 and included age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation for clozapine-treated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Clozapine dosage and laboratory results were recorded at 12-month intervals. Results: At the time of clozapine initiation, the mean +/- SD age of the 96 patients studied was 36.5 +/- 7.9 years; 28% (N = 27) were women. The Kaplan-Meier estimate for 10-year mortality from cardiovascular disease was 9%. African American and Hispanic American patients exhibited elevated risk of cardiovascular disease-related mortality (odds ratio [OR] = 7.2, p =.09; OR = 11.3, p =.04, respectively) compared to white patients. Body mass index (BMI) significantly increased the odds ratio of mortality (OR = 1.2, p <.01). The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p =.027) and African American (OR = 11.5, p =.0001) patients showed elevated risks of developing diabetes mellitus compared to white patients. Additionally, BMI (OR = 1.11, p =.0006), total cholesterol level (OR = 1.006, p =.04), and serum triglyceride level (OR = 1.002, p =.04) modestly increased the odds ratio for the development of diabetes mellitus. Conclusions: These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia.