The efficacy and safety of fluoxetine versus placebo for stroke recovery: a meta-analysis of randomized controlled trials

BackgroundFluoxetine is one of the selective serotonin reuptake inhibitors that can improve motor and function recovery after a stroke. Several randomized controlled trials (RCTs) have investigated the efficacy and safety of fluoxetine compared to placebo in post-stroke recovery. However, the results are still controversial.AimThis meta-analysis aimed to provide an updated analysis of the efficacy and safety of fluoxetine versus placebo in post-stroke recovery.MethodRCTs were searched from electronic databases of PubMed, Embase, Clinical Trials, and the Cochrane Central Register of Controlled Trials from inception until July 2022. Google Scholar and the reference lists of included studies were screened to identify additional studies. Outcomes were analyzed using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI).ResultsFourteen RCTs (6584 patients) were included. The fluoxetine group showed a significantly higher Fugl-Meyer motor scale (FMMS) score than the placebo group (MD 15.93, 95%CI 9.76-22.7, P < 0.01). No significant differences were observed in the modified Rankin Scale (mRS) (mRS <= 2, RR 1.00, 95%CI 0.88-1.15, P = 0.95), the Barthel index (MD 12.11, 95%CI - 0.71 to 24.92, P = 0.06), and the National Institutes of Health Stroke Scale scores (MD - 0.19, 95%CI - 0.43 to 0.04, P = 0.1) between the two groups. The fluoxetine group showed a lower rate of depression or anxiety than the placebo group (RR 0.67, 95% CI 0.49-0.92, P < 0.05). There were no significant differences between the groups regarding gastrointestinal adverse reactions (P > 0.05), drowsiness (P > 0.05) or insomnia (P > 0.05).ConclusionFluoxetine improved FMMS and reduced anxiety and depression. More well-designed and large sample-size RCTs are required to further analyze the efficacy of fluoxetine in post-stroke recovery.