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

Abstract

Background
Three large randomised controlled trials of fluoxetine for stroke recovery have been performed. We perfomed an individual patient data meta-analysis (IPDM) on the combined data.
Methods
Fixed effects meta-analyses was performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined.
Findings
The three trials recruited a combined total of 5907 people (mean age 69∙5 years (SD 12∙3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, UK, Sweden and Vietnam; and randomized them to fluoxetine 20mg daily or matching placebo for 6 months. Data on 5833 (98∙75%) were available at 6 months. 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 6 months, 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 hyponatraemia (1∙22% vs 0∙61%, p=0∙01) but reduced new depression (10∙05% vs 13∙42%, p<0∙0001). At 12 months, there was no difference in adjusted mRS (n=5760; COR 0∙98, 95% CI 0∙89 to 1∙07). Sensitivity analyses gave the same results.
Interpretation
Fluoxetine 20mg daily for six months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.