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

Gillian Mead*, Catriona Graham, Erik Lundström, Graeme Hankey, Maree Hackett, Laurent Billot, Per Näsman, John Forbes, Martin Dennis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

We collaboratively designed three large trials of fluoxetine for stroke recovery to facilitate an individual patient data meta-analysis (IPDM).
We performed fixed effects meta-analyses 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.
We recruited 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. 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.
Fluoxetine 20mg daily for six months did not improve functional recovery. It increased seizures, falls with injury, bone fractures but reduced depression frequency at 6 months.
Trial Funding
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
Original languageEnglish
JournalInternational Journal of Stroke
Early online date18 Mar 2024
Publication statusE-pub ahead of print - 18 Mar 2024


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