7 January 2005. A report in the January issue of the Archives of General Psychiatry reinforces earlier observations that some antipsychotic drugs may increase the risk for, or even cause, diabetes in patients with schizophrenia. Since these drugs are often prescribed to patients with Alzheimer disease, and given the evidence of a link between diabetes and AD, this issue may become an important one in the AD clinical world, as well.
Psychiatrists have reported a trend toward greater incidence of type 2 ("insulin-resistant") diabetes mellitus in schizophrenia patients who take some of the newer, so-called "atypical," antipsychotic drugs. However, it is unclear whether this would be a direct effect of the drugs on glucose metabolism, or a secondary effect of the drugs promoting diabetes risk factors such as obesity or lipid abnormalities. David C. Henderson and colleagues at Massachusetts General Hospital and Harvard University assessed glucose function in a group of 36 non-obese patients with schizophrenia. They found that the atypical drugs olanzapine and clozapine increase insulin resistance and impair glucose effectiveness, relative to the drug risperidone, also in the atypical category. Since these patients were not obese, and had no differences in their lipid levels among the three drug groups, the researchers suggest that the drugs affect glucose metabolism directly.
Insulin resistance is the failure of cells to respond to insulin's signals to take up glucose from the blood, and it represents a major risk factor for type 2 diabetes. But interestingly, it may also be a risk factor for AD (see ARF related news story). The possibility that elderly patients taking antipsychotic drugs for behavioral symptoms, especially due to dementia, may be at increased risk of diabetes has been noted by some researchers (Lee et al., 2004). The doses given to these patients are typically less than those taken by younger people with schizophrenia, but altered pharmacokinetics may put older people at relatively greater risk.
Regarding possible mechanisms, the authors note, "The lower glucose effectiveness values observed in patients treated with clozapine and olanzapine could result from several mechanisms, including reduced functioning of glucose transporters or an impairment in the suppression of hepatic glucose production." However, they also point out the possibility that schizophrenia itself might be associated with insulin resistance and diabetes, independent of any effect of the drugs.—Hakon Heimer.
Henderson DC, Cagliero E, Copeland PM, Borba CP, Evins E, Hayden D, Weber MT, Anderson EJ, Allison DB, Daley TB, Schoenfeld D, Goff DC. Glucose Metabolism in Patients With Schizophrenia Treated With Atypical Antipsychotic Agents: A Frequently Sampled Intravenous Glucose Tolerance Test and Minimal Model Analysis. Arch Gen Psychiatry. 2005 Jan;62(1):19-28. Abstract