Clozapine and olanzapine appear to cause significant insulin resistance in non-obese patients, whereas risperidone does not appear to alter glucose tolerance testing, according to an article in the January issue of the Archives of General Psychiatry.

“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.”

David C. Henderson, MD, and his American colleagues evaluated 36 non-obese outpatients with schizophrenia or schizoaffective disorder who were treated with clozapine, olanzapine, or 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 non-obese 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 wrote: “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.”