Use of selective serotonin reuptake inhibitors and risk of stroke: a systematic review and meta-analysis

Since several studies have inconsistently reported the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of stroke, we performed a meta-analysis on this issue. We identified studies by searching three electronic databases (MEDLINE, EMBASE, and the Cochrane Library) from their inception to August, 2013. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirteen relevant studies (three case-control, six nested case-control, and four cohort studies) were finally included in our study. In our meta-analyses, the use of SSRIs was associated with an increased risk of all types of stroke [adjusted odds ratio (aOR), 1.40; 95 % confidence interval (CI), 1.09-1.80], ischemic stroke (aOR 1.48; 95 % CI 1.08-2.02), and hemorrhagic stroke (aOR 1.32; 95 % CI 1.02-1.71). Between the two subtypes of hemorrhagic stroke, that is, intracerebral and subarachnoid, the increased risk of intracerebral hemorrhage was associated with the use of SSRIs (aOR 1.30; 95 % CI 1.02-1.67). When the analysis was restricted to the studies in which potential confounding by depression was considered, the risks were still higher in SSRI users than in non-users and the heterogeneities among studies were significantly decreased. Since there was heterogeneity among studies and a possible confounding effect from depression could not be fully excluded, further well-designed studies are needed to confirm this association.