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Exposure to Antipsychotics and Risk for Stroke

Use of antipsychotics, especially atypical drugs, raises risk for stroke, and this risk is higher in patients with dementia than in those without.

During 2002, analysis of clinical trial data raised concerns that exposure to the atypical antipsychotic drug risperidone led to excess stroke risk in dementia patients. However, whether stroke risk associated with antipsychotic drug exposure differs among people with or without dementia is unknown. Using a large database that predated these concerns, U.K. investigators compared stroke incidence during periods of exposure and nonexposure to antipsychotic drugs within individual patients who had or did not have dementia.

Of 6790 patients who had first strokes and were prescribed antipsychotic drugs between 1988 and 2002, 6334 were prescribed at least one typical drug (most commonly phenothiazines), and 905 patients were prescribed at least one atypical drug (most commonly risperidone). The median age at first exposure to any antipsychotic drug was 80, and the median age at first stroke was 81. Exposure to any antipsychotic drug was associated with significantly higher risk for stroke (rate ratio, 1.73); excess risk was noted for both typical drugs (RR, 1.69) and atypical drugs (RR, 2.32). In patients with dementia, exposure to any antipsychotic drug was associated with a rate ratio for stroke of 3.50, whereas, in patients without dementia, the rate ratio was 1.41. In all analyzed groups, the rate ratios decreased towards 1.0 during the 5 months after treatment ended.

Comment: Exposure to antipsychotic drugs is associated with excess risk for stroke, and this risk appears to be higher among patients with dementia than among those without dementia. Notably, the mechanism by which these drugs raise stroke risk is unclear. Nevertheless, these results should serve as yet another red flag for clinicians, joining those of recent studies that showed minimal efficacy in patients with dementia who received antipsychotic drugs (JW Dec 28 2006).

— Paul S. Mueller, MD, MPH, FACP

Published in Journal Watch General Medicine September 11, 2008

Citation(s):

Douglas IJ and Smeeth L. Exposure to antipsychotics and risk of stroke: Self controlled case series study. BMJ 2008 Aug 28; 337:a1227. (http://dx.doi.org/10.1136/bmj.a1227)

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