Selective Serotonin Reuptake Inhibitors and the Risk of Stroke: A Population-Based Case-Control Study

Abstract

Background and Purpose— Selective serotonin reuptake inhibitors (SSRIs) have been associated with increased risk of bleeding complications, possibly as a result of inhibition of platelet aggregation. Little is known about the risk of intracerebral hemorrhage in users of SSRIs and whether the effect on platelet aggregation reduces the risk of ischemic stroke. We used population-based data to estimate the risk of hemorrhagic and ischemic stroke in users of SSRIs. Methods— We performed a nested case-control study in Funen County (465 000 inhabitants), Denmark. All patients with a first-ever stroke discharge diagnosis in the period of 1994 to 1999 were identified, and a validated diagnosis of stroke was reached in 4765 cases. In all, 40 000 controls were randomly selected from the background population. Information on drug use for cases and controls was retrieved from a prescription registry with full coverage of the county. Odds ratios were adjusted for age, sex, calendar year, and use of other medication. To evaluate the effect of various potential confounders not recorded in the register data, we performed separate analyses on data from 2 large population-based surveys with more detailed information on risk factors. Results— Of 659 patients with hemorrhagic stroke, 21 were current users of SSRIs. The adjusted odds ratio of hemorrhagic stroke in current SSRI users compared with never users was 1.0 [95% confidence interval (CI), 0.6 to 1.6]. Of 2717 patients with ischemic stroke, 100 were current users of SSRIs, and the adjusted odds ratio of ischemic stroke in cases compared with controls was 1.1 (95% CI, 0.9 to 1.4). The survey data indicated that additional confounder control would not have led to an increase in the relative risk estimates. Conclusions— Current exposure to SSRIs is not associated with increased risk of intracerebral hemorrhage and is probably not associated with a decreased risk of ischemic stroke.