ScienceDaily (Jan. 5, 2005) — CHICAGO -- Patients treated with the atypical anti-psychotic agents clozapine and olanzapine may be at an increased risk for insulin resistance, which is a major risk factor for diabetes mellitus, according to a study in the January issue of the Archives of General Psychiatry, one of the JAMA/Archives journals.

"Compared with the general population, life expectancy in patients with schizophrenia is shorter by as much as 20 percent, attributable to higher rates of suicide, accidental deaths, and natural causes such as cardiovascular disease, infectious disease, and endocrine disorders," according to background information in the article. "Recently, the newer 'atypical' antipsychotic agents have been linked to several forms of morbidity, including obesity; hyperlipidemia; type 2 diabetes mellitus; and diabetic ketoacidosis [a severe complication of diabetes]."

David C. Henderson, M.D., from Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues, evaluated 36 non-obese outpatients with schizophrenia or schizoaffective disorder who were treated with clozapine, olanzapine, or another medication, risperidone. Participants were given a diet to follow to maintain body weight and were told to fast for 12 hours prior to undergoing a frequently sampled intravenous glucose tolerance test.

"Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects," the researchers found.

In conclusion, the authors write: "Psychiatrists and primary care professionals should be aware that patients treated with clozapine and olanzapine may be at increased risk for insulin resistance, even if not obese. Insulin resistance is associated with hyperlipidemia, hypertension, and cardiovascular disease and over time may increase the risk for diabetes mellitus in vulnerable individuals. Patients treated with these agents should be routinely screened, counseled to reduce risk, and provided early interventions."

(Arch Gen Psychiatry. 2005;62:19–28. Available post-embargo at archgenpsychiatry.com)

Editor's Note: This study was supported by a grant from the National Institutes of Health General Clinical Research Center, Bethesda, Md.; a Young Investigator Award from the National Alliance for Research of Schizophrenia and Depression, Great Neck, N.Y. (Dr. Henderson); and an Investigator-Initiated Independent Research Grant from Janssen Pharmaceutica, Beerse, Belgium.

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Adapted from materials provided by Journal Of The American Medical Association.

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