Age, Antipsychotics, and the Risk of Ischemic Stroke in the Veterans Health Administration

Abstract

Background and Purpose— Time-dependent effects of antipsychotics on risk of stroke and potential effect modification by age have not been fully investigated. A case–case–time–control design uses within- and between-case comparisons to evaluate short-term effects at the same time as adjusting for unmeasured time-invariant confounders and exposure-time trends. Methods— We conducted a case–case–time–control design study using data from the Veterans Health Administration. Veterans with inpatient hospitalizations for ischemic stroke between 2002 and 2007 were included. For every stroke case, the “current” exposure period was defined as 1 to 30 days before hospitalization and the “reference” period as 91 to 120 days before hospitalization. Exposure during the current period was compared with exposure during the reference period within cases. Exposure-time trend-adjusted estimates of the effect of antipsychotic exposure on risk of stroke were obtained by dividing exposure odds for antipsychotic exposure by average exposure odds for other medications over the same time period among the same cases. Results— After adjusting for exposure-time trends, odds of stroke were 1.8 (95% CI, (1.7–1.9) times higher when exposed to antipsychotics than when unexposed. Age-stratified estimates suggest a greater triggering effect of antipsychotics among older patients. Conclusions— Exposure to antipsychotics may be a proximal trigger for stroke. Elevation in risk is apparent after brief exposure to antipsychotics.