Objective: To determine whether fluoxetine, at any dose, given within the first year after stroke to patients who did not have to have mood disorders at randomization reduced disability, dependency, neurological deficits and fatigue; improved motor function, mood, and cognition at the end of treatment and follow-up, with the same number or fewer adverse effects.
Methods: Searches (from 2012) in July 2018 included databases, trials registers, reference lists, and contact with experts. Co-primary outcomes were dependence and disability. Dichotomous data were synthesized using risk ratios (RR) and continuous data using standardized mean differences (SMD). Quality was appraised using Cochrane risk of bias methods. Sensitivity analyses explored influence of study quality.
Results: The searches identified 3414 references of which 499 full texts were assessed for eligibility. Six new completed RCTs (n = 3710) were eligible, and were added to the seven trials identified in a 2012 Cochrane review (total: 13 trials, n = 4145). There was no difference in the proportion independent (3 trials, n = 3249, 36.6% fluoxetine vs. 36.7% control; RR 1.00, 95% confidence interval 0.91 to 1.09, p = 0.99, I2 = 78%) nor in disability (7 trials n = 3404, SMD 0.05, -0.02 to 0.12 p = 0.15, I2 = 81%) at end of treatment. Fluoxetine was associated with better neurological scores and less depression. Among the four (n = 3283) high-quality RCTs, the only difference between groups was lower depression scores with fluoxetine.
Conclusion: This class I evidence demonstrates that fluoxetine does not reduce disability and dependency after stroke but improves depression.
Keywords: Stroke; fluoxetine; recovery; rehabilitation.