No abstract

The goal of this 21-year naturalistic study of clozapine treated patients was to examine the cardiovascular risk factors following clozapine initiation and resultant mortality estimates from cardiovascular disease. Data was collected from medical records of clozapine treated patients with schizophrenia or schizoaffective disorder from January 1992 to February 2012. Demographics, clozapine dosage and laboratory results were extracted at 12-month intervals. At clozapine initiation, the mean age of 96 patients was 36.4 years ±7.6 years; N=27(28%) were women. The mean duration of clozapine use was 13 years. The Kaplan-Meier estimate for 21-year cardiovascular events was 29%, while the Kaplan-Meier estimate for 21-year mortality from cardiovascular disease was 10%. The mean cardiovascular risk increased during the first ten years (p<.01), while a slight decrease occurred beyond ten years (p<.01). Patients involved in cardiometabolic research showed a greater decrease in cardiovascular risk factors over 21 years (p = .05). The Kaplan-Meier estimate for 21-year all-cause mortality was 22%. Forty-one patients were diagnosed with diabetes (42.7%), compared to a nationwide prevalence of 13.7% in a similar age group. These results support the hypothesis that clozapine-treated patients are at risk for cardiovascular events and death secondary to an increased risk of medical disorders. Interventions that target weight loss, smoking cessation, and lipid profile improvement may alleviate the increased risk of cardiovascular mortality.

Objective People with schizophrenia are at greater risk for cardiovascular disease and their overallmortality rate is elevated compared to the general population. The metabolic side effects of antipsychotic medications have been widely studied; however, the effect of adding conventional mood stabilizers, such as lithium and valproate, to antipsychotic medication has not been assessed in terms of metabolic risk. The primary purpose of this secondary analysis was to examine whether treatment with lithium or valproate in addition to a second-generation antipsychotic is associated with poorer metabolic outcomes than treatment with a second-generation antipsychotic without lithium or depakote. Methods Baseline data from 3 studies, which included measurement of body mass index, waist circumference, fasting glucose, insulin, homeostatic model assessment of insulin resistance, insulin sensitivity index, glucose utilization, and acute insulin response to glucose, were included in the analysis. Results No differences were found between those taking lithium or valproate and those who were not in terms of fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance. Insulin sensitivity was lower among participants taking lithium or valproate. Participants taking lithium or valproate had a higher body mass index than those not taking conventional mood stabilizers, although the difference did not reach statistical significance. Conclusions These cross-sectional findings suggest it may be beneficial to monitor insulin sensitivity and body mass index in patients taking lithium or valproate in combination with a second-generation antipsychotic.