Two drugs commonly prescribed for schizophrenia - clozapine and olanzapine - may carry a small risk of an increased risk of diabetes, new research shows.

The study of nearly 57,000 schizophrenia patients in the Veterans Affairs (VA) health system found that just over 7 percent developed diabetes over 1 to 2 years of follow-up. The risk of diabetes was higher among those who were on the antipsychotic drugs clozapine or olanzapine for at least 3 months during the study period.

Both of the drugs belong to a class of medications known as atypical antipsychotics, which are newer schizophrenia drugs developed in the 1990s that carry fewer side effects than conventional antipsychotics. They are now considered first-line therapy for the disorder.

Still, past research has suggested that these newer drugs may raise the risk of diabetes, and the U.S. Food and Drug Administration has already instructed manufacturers to place a warning on product labels.

The FDA decision applies to all atypical antipsychotics, but the new findings suggest that the risk may be real only for clozapine and olanzapine, study co-author Dr. Douglas L. Leslie told Reuters Health.

And even that risk appears small, the study found. For instance, the “attributable risk” of diabetes associated with clozapine was about 2 percent.

That means that of clozapine patients who developed diabetes during the study, 2 percent would not have become diabetic if they been on a conventional antipsychotic, explained Leslie, an assistant professor of psychiatry at the Yale School of Medicine in New Haven, Connecticut.

He and colleague Dr. Robert A. Rosenheck report the findings in the September issue of the American Journal of Psychiatry.

Atypical antipsychotic drugs are thought to raise the odds of type 2 diabetes by promoting weight gain. A number of reports have suggested that people on these medications have a higher-than-average prevalence of diabetes, but the studies did not follow patients over time to document new cases of the disease.

Leslie and Rosenheck used VA data to follow 57,849 schizophrenia patients who had been treated with an antipsychotic for at least three months. By the end of the study, 4,132 patients were newly diagnosed with diabetes - at an annual rate of 4.4 percent, which is much higher than the 0.6-percent rate in the general public.

While clozapine and olanzapine seemed to account for some of this risk, the researchers note that it’s unclear how much of the risk could have been due to the underlying schizophrenia, poorer overall health or other factors.

But, according to Leslie, doctors can use what’s known about the risk associated with schizophrenia medications to monitor patients for weight gain and possibly head off the development of diabetes.

SOURCE: American Journal of Psychiatry, September 2004.