Effect of antidepressants on motor and functional recovery in stroke: a systematic review and meta-analysis

Despite significant progress in acute stroke management, the burden of persistent motor impairments necessitates ongoing research into novel therapeutic strategies. Our study aims to study if antidepressants can effectively improve the motor function and functional independence in patients after stroke.

This meta-analysis encompassed Randomized Controlled Trials (RCTs) that enrolled adult stroke patients and compared any antidepressant drug against placebo, and reporting motor outcomes. We excluded studies which reported only cognitive outcomes or single arm studies with no comparator. We searched PubMed, Scopus, Cochrane, and Web of Science for records from inception up to August 2024. Outcomes data were pooled as standardized mean differences (SMDs) with the corresponding 95% confidence intervals (CI). Risk of Bias 2 (RoB2) tool was considered for quality assessment of the included studies.

The preliminary search yielded 22 articles. A total of 11,396 patients were included, with a majority being elderly. Anti-depressants, primarily fluoxetine and citalopram, significantly improved Fugl Meyer Motor scale Scores (FMMS) at the endpoint (SMD = 0.79, 95%CI [0.056, 1.02], p-value < 0.00001) and change from baseline (SMD = 0.75, 95%CI [0.27, 1.24], p-value = 0.002), suggesting a substantial positive effect equivalent to a large effect size, potentially reflecting significant improvements in motor control and function. There wasn't a significant subgroup difference between fluoxetine, citalopram, and selegiline. Also, Barthel index (BI) scores endpoints were significantly improved by antidepressants (SMD = 0.54, 95%CI [0.12, 0.96], p-value = 0.01) and change from baseline (SMD = 0.46, 95%CI [0.02, 0.9], p-value = 0.04), indicating a moderate positive effect, likely representing noticeable gains in independence for activities of daily living. There was a significant difference in both BI endpoints score and change from baseline (P < 0.00001) between subgroups favoring escitalopram. However, anti-depressants did not improve modified Rankin Scale (mRS) Scores (SMD = 0.06, 95%CI [-0.01, 0.12], p-value = 0.08). There wasn't a significant subgroup difference between fluoxetine and citalopram (p-value = 0.17). Based on RoB2, 12 studies were rated as having an overall low risk of bias, four were rated as having some concerns, and six were assessed as high risk.

Certain antidepressants may enhance motor performance and independence in performing activities of daily living during post-stroke recovery among elderly patients. Fluoxetine was the most common antidepressant described in the literature with significant improvement in motor (FMMS) functional (BI) scales. However, substantial heterogeneity and potential study biases warrant cautious interpretation. Rigorous, large-scale RCTs are necessary to verify these findings and establish long-term safety profiles. They will also help define the optimal therapeutic strategies before routine clinical use is considered.