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.


METHODS
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.
Henderson
David C
DC
Schizophrenia Program, MGH Weight Center, Massachusetts General Hospital, Boston, MA 02114, USA. dchenderson@partners.org
Nguyen
Dana D
DD
Copeland
Paul M
PM
Hayden
Doug L
DL
Borba
Christina P
CP
Louie
Pearl M
PM
Freudenreich
Oliver
O
Evins
A Eden
AE
Cather
Corrine
C
Goff
Donald C
DC
D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality*; D002423:Cause of Death; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000453:epidemiology*; D005260:Female; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000453:epidemiology*; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000453:epidemiology; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000453:epidemiology; D012307:Risk Factors; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy / Q000453:epidemiology; D016019:Survival Analysis
D014150:Antipsychotic Agents; D003024:Clozapine; D018967:Risperidone