Anti-Psychotic Drugs May Reduce -- Not Increase -- Risk of Diabetes in Mentally Ill Patients, UB Studies Show

BUFFALO, N.Y. -- Two related University at Buffalo studies examining the incidence of diabetes and related conditions among patients suffering from schizophrenia or bipolar disorder indicate that it is the illness -- not the atypical antipsychotic medications used to treat the disorders -- that contributes to the increased incidence of diabetes in these patients.

The findings suggest that the atypical antipsychotics, second-generation antipsychotic medications that became available after 1991, such as Clozaril (clozapine), Zyprexa (olanzapine), Risperdal (risperidone) and Seroquel (quetiapine fumarate), may actually have a protective effect against diabetes.

The results seem to contradict growing fears that antipsychotic medications cause the increased rate of diabetes in patients with these mental illnesses, fears that recently led Japan and the European Union to require one atypical antipsychotic to include warnings about diabetes-related complications in its product information sheets.

The studies were conducted by researchers in the Department of Pharmacy Practice in the UB School of Pharmacy and Pharmaceutical Sciences.

One study will be presented May 2 in a poster session at the annual conference of the College of Psychiatric and Neurologic Pharmacists in Charleston, S.C. The other will be presented May 21 in a poster session at the annual conference of the American Psychiatric Association in San Francisco.

Based on the findings, the UB researchers conclude that psychiatric care for patients with the two disorders should be modified to include routine screening for diabetes (adult onset or type 2), hypertension and obesity.

They also suggest that severe mental illness should be listed, along with family history of diabetes, as a primary risk factor for diabetes.

"According to our findings in these studies, an association between schizophrenia and bipolar disorder and diabetes seems to exist independent of any antipsychotic use," said Terrance Bellnier, R.Ph., assistant clinical professor of pharmacy practice, director of psychiatric pharmacy practice at UB and co-author of the study.

"The question is, whether these drugs induce diabetes at the same rate, or it's the mental illness itself -- what we're using the drugs for -- that induces diabetes," Bellnier said. "That's the question we tried to answer."

More than 2 million Americans suffer from schizophrenia and the same number suffer from bipolar disorder.

Diabetes is estimated to affect more than 15 million Americans.

Data in the study to be presented at the annual conference of the American Psychiatric Association demonstrate that an increased incidence of diabetes among patients with schizophrenia or bipolar disorder predates the use of antipsychotic medications to treat the disorders.

That study, based on a retrospective review of medical data for 569 randomly selected patients with the two disorders admitted to a state psychiatric hospital between 1940 and 1950, before antipsychotic medications were available, found that metabolic disturbances were significantly greater in those patients than among the general population.

According to the results, the rate of diabetes among the patients was 20.9 percent, or 10 times that reported at that time for the general population. The incidence of hypertension was 29.1 percent, compared to 16.5 percent in the general population, and the incidence of "overweight" was 28.2 percent versus 21.8 percent in the general population.

The other UB study compared in a matched-pair analysis the data for these untreated patients with data from 569 patients admitted to a state psychiatric hospital between 1999 and 2002, all of whom were treated with atypical antipsychotics.

In patients treated with the medications, the rate of diabetes was 10.4 percent, half of what was reported in the group that received no medication, and slightly more than twice the rate reported in the general population.

The second study also found that the incidence of hypertension in the treated patients was 15.6 percent, compared to 7.2 percent in the general population, while hypertension in the untreated population was nearly twice as prevalent.

"When you effectively treat schizophrenia and bipolar disorder, you reduce most of these other metabolic risk factors," said Bellnier.

"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 may actually have a protective effect," he said.

According to Bellnier, it is possible that hypercortisolemia, the elevated levels of cortisol -- the hormone secreted by the adrenal gland in response to stress -- may contribute to metabolic syndrome in severely mentally ill patients.

"When you effectively treat these disorders and therefore reduce the psychotic and manic episodes associated with the elevation of cortisol, then you may also be protecting them from diabetes," he said.

According to the study's authors, one metabolic disturbance did increase with the use of antipsychotic medications and that was the incidence of patients considered overweight.

While untreated patients had an incidence of "overweight" of 28.2 percent, versus 21.8 percent in the general population at that time, the incidence of "overweight" in the treated population was 68.6 percent, compared to 37 percent in the general population at that time.

Bellnier said this striking statistic provides strong evidence of a connection between the use of multiple psychotrophics, such as antipsychotics, antidepressants, mood stabilizers and anticonvulsants, and the incidence of overweight in severely mentally ill patients.

Still, he noted, this single metabolic disturbance does not account for the incidence of diabetes among these patients.

"Obesity alone does not explain it. You can be heavy for years and not develop diabetes," he said.

Based on their findings, the UB researchers conclude that psychiatric care should be modified to include routine screening for diabetes, hypertension and obesity.

"An enormous amount of energy has been wasted in trying to blame one drug over another as the cause of this higher risk," said Bellnier. "What we need to do now is to raise the bar a little in caring for these patients so that they now receive the same routine screening for diabetes and related conditions that the general population receives."

According to Bellnier, advocates for the mentally ill have, for good reason, focused primarily on good psychiatric care.

"But we've moved into an era where that care is available," said Bellnier. "These patients are predisposed to metabolic disturbances and they deserve the same care that everyone else gets. And ultimately, when they start getting preventive care or treatment for these conditions, instead of emergency care because their diabetes has never been treated, there will be a major economic benefit to the health-care system as well."

Funded by UB, the studies were co-authored by Bellnier's post-doctoral fellow, Adam Decatur, Pharm.D.; Kashinath Patil, M.D., assistant clinical professor, Department of Psychiatry, University of Rochester, and Tulio Ortega, M.D., adjunct assistant clinical professor, UB Department of Pharmacy Practice.