Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke

Background: Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data.

Methods: Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6months), and secondary outcomes common to the individual trials. As a sensitivity analysis, sum?mary statistics from each trial were created and combined.

Findings: The three trials recruited a combined total of 5907 people (mean age 69.5years (SD 12.3), 2256 (38%) females, 2–15days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20mg daily or matching placebo for 6months. Data on 5833 (98.75%) were available at 6months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p=0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p=0.03), falls with injury (6.26% vs 4.51%, p=0.03), fractures (3.15% vs 1.39%, p<0.0001) and hyponatre?mia (1.22% vs 0.61%, p=0.01) but reduced new depression (10.05% vs 13.42%, p<0.0001). At 12months, there was no difference in adjusted mRS (n=5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results.

Interpretation: Fluoxetine 20mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6months.