SAN FRANCISCO AND CHARLESTON, SC— Based on clinical trial findings, concern has been growing that atypical antipsychotics may precipitate type 2 diabetes mellitus in patients taking those medications for severe mental illness. Japan and the European Union have even required the product information sheets of at least one atypical antipsychotic to contain warnings about the possibility of diabetic complications.

However, two recent studies found no link between atypical antipsychotics and diabetes. “We found instead that schizophrenia and bipolar disorder are associated with diabetes independently of antipsychotic use,” said Terrance Bellnier, RPh, MPA, coauthor of both studies and Clinical Assistant Professor at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

One of the studies, presented at the American Psychiatric Association’s annual meeting, was a retrospective review of 569 randomly selected patients with schizophrenia or bipolar disorder. The investigators found significantly higher rates of metabolic disorders such as diabetes in the study population than in the general population. Importantly, Professor Bellnier noted, the patients had been hospitalized for mental illness between 1940 and 1950—years before antipsychotic drugs became available.

During that interval, about 21% of the patients had diabetes and 29% were hypertensive; about 28% were overweight. By contrast, the rates of those conditions in the general population were markedly lower, at about 2%, 16.5%, and 22%, respectively.

The fact that schizophrenic and bipolar patients do not typically eat well and are often in poor overall health could help to explain their increased rate of metabolic disorders. Some recent smaller studies suggest that these patients also have significant hypercortisolemia in response to psychosocial stress. “If you elevate cortisol, then you increase visceral fat, which is a risk factor for diabetes,” said Professor Bellnier.

Lack of access to atypical antipsychotics may have amplified the study population’s cortisol-related risk of metabolic disease. Indeed, some investigators believe that these agents may actually help to suppress cortisol by enhancing adaptability to psychosocial stress; the second study by Professor Bellnier and colleagues appears to support that hypothesis.

In this study, presented at the Sixth Annual Meeting of the College of Psychiatric and Neurologic Pharmacists, the subjects of the retrospective review were compared to an equal number of patients admitted to a state psychiatric hospital for bipolar disorder or schizophrenia between 1999 and 2002. All of the contemporary patients received atypical antipsychotic therapy.

Their rate of diabetes was slightly above 10% or about half that of the 1940–1950 cohort, none of whom received antipsychotics. The contemporary patients also had a lower rate of hypertension, about 16%, although the proportion that was overweight (69%) was more than double—an amount Professor Bellnier described as “strikingly high.” This may be related to the use of multiple psychotropic medications in the severely mentally ill, he suggested, adding that further research is necessary to determine if the protective effect is due to a decline in cortisol.

Taken together, the two studies strongly suggest that atypical antipsychotic therapy protects against, not causes, most metabolic disorders. “While the incidence of diabetes has actually gone up in the general population since the 1940s and 1950s, our study shows it has gone down significantly in patients being treated with antipsychotic medications, so these antipsychotic drugs appear to reduce the risk of diabetes,” Professor Bellnier said.

It is time, he concluded, for severe mental illness to be considered a primary risk factor for type 2 diabetes mellitus. Furthermore, psychiatric care for patients with schizophrenia or bipolar disorder must now include routine screening for diabetes, hypertension, and weight problems, he urged.

—Timothy Begany

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