University of Limerick
Forbes_2024_Individual.pdf (538.73 kB)

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

Download (538.73 kB)
journal contribution
posted on 2024-05-08, 13:17 authored by Gillian Mead, Catriona Graham, Erik Lundström, Graeme J Hankey, Maree L Hackett, Laurent Billot, Per Näsman, John F ForbesJohn F Forbes, Martin Dennis

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.


Other Funding information

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Stroke Association, National Institute of Health Research, Australian Government National Health and Medical Research Council, Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Brain Foundation, Swedish Society of Medicine, King Gustav V and Queen Victoria’s Foundation of Freemasons, and STROKE-Riksförbundet

Sustainable development goals

  • (3) Good Health and Well-being
  • (17) Partnerships for the Goals

Department or School

  • School of Medicine

Usage metrics

    University of Limerick



    Ref. manager