Safety and Efficacy of SSRIs in Improving Poststroke Recovery: A Systematic Review and Meta-Analysis

Background Several studies investigated the role of selective serotonin reuptake inhibitors (SSRIs) in improving poststroke recovery; thus, we have decided to conduct this systematic review and meta-analysis to investigate the efficacy and safety of SSRIs in poststroke recovery. Methods and Results In this meta-analysis we searched the following databases: PubMed, Cochrane, Scopus, and Google Scholar. The studies were included if they were placebo-controlled trials in design and reported SSRIs' effects on poststroke depression, anxiety, disability, dependence, motor abilities, and cognitive functions. The quality of the included studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The search yielded 44 articles that included 16 164 patients, and about half of the participants were treated with SSRIs. Our results showed that SSRIs had a significant effect on preventing depression (weighted mean difference [WMD], -7.05 [95% CI, -11.78 to -2.31]), treating depression according to the Hamilton Rating Scale for Depression score (WMD, -1.45 [95% CI, -2.77 to -0.14]), anxiety (relative risk, 0.23 [95% CI, 0.09-0.61]), dependence (WMD, 8.86 [95% CI, 1.23-16.48]), motor abilities according to National Institutes of Health Stroke Scale score (WMD, -0.79 [95% CI, -1.42 to -0.15]), and cognitive functions (WMD, 1.00 [95% CI, 0.12-1.89]). On the other hand, no significant effect of SSRIs on disability was observed. Additionally, we found that treating with SSRIs increased the risk of seizures (relative risk, 1.44 [95% CI, 1.13-1.83]), whereas there was no difference in the incidence of gastrointestinal symptoms or bleeding between SSRIs and a placebo. Conclusions Our study showed that SSRIs are effective in preventing and treating depression, and improving anxiety, motor function, cognitive function, and dependence in patients after stroke. These benefits were only reproducible with the citalopram subanalysis but not fluoxetine. Further well-conducted placebo-controlled trials are needed to investigate the safety and efficacy of citalopram among patients after stroke. Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021285766.