The Efficacy and Tolerability of Selective Serotonin Reuptake Inhibitors for Motor Recovery in Non-depressed Patients After Acute Stroke: A Meta-Analysis

Objective: To explore the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) for motor recovery in non-depressed patients after acute stroke. Methods: According to the predefined retrieval strategy, multiple electronic databases were searched for randomized controlled trials (RCTs) that met the inclusion criteria. The primary efficacy outcome was measured by Fugl-Meyer Motor Scale (FMMS) score and the indicators of tolerability included withdrawal rate and the incidence of adverse events (AEs). Results: 10RCTs were included, the pooled analyses showed patients who received fluoxetine (endpoint: MD = 21.17, 95% CI 14.13–28.21, P < 0.00001; mean change: MD = 16.27, 95% CI 10.05–22.50, P < 0.00001) and citalopram (endpoint: MD = 22.93, 95% CI 11.13–34.73, P = 0.0001; mean change: MD = 24.06, 95% CI 10.47–37.65, P = 0.0005) experienced greater improvement in FMMS score. There was no evident difference in total withdrawal rate (fluoxetine: OR = 1.11, 95% CI 0.90–1.27, P = 1.38; citalopram: OR = 0.94, 95% CI 0.69–1.28, P = 0.71; escitalopram: OR = 0.87, 95% CI 0.58–1.28, P = 0.47) between two groups. Besides, the incidence of hyponatremia (OR = 2.01, 95% CI 1.16–3.50, P = 0.01), seizure (OR = 1.46, 95% CI 1.03–2.08, P = 0.04) and fracture (OR = 2.34, 95% CI 1.61–3.40, P < 0.00001) in the fluoxetine group was higher than in the placebo group. Conclusions: Fluoxetine and citalopram can promote motor recovery in non-depressed patients with acute stroke, but it is necessary to pay attention to the possible AEs of fluoxetine, such as hyponatremia, seizure and fracture. Systematic Review Registration: PROSPERO, identifier [CRD42021227452].