Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

FOCUS Trial Collaboration

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BACKGROUND: Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.

METHODS: FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.

FINDINGS: Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839-1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26-6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38-2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.

INTERPRETATION: Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.

FUNDING: UK Stroke Association and NIHR Health Technology Assessment Programme.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalThe Lancet
Issue number10168
Early online date5 Dec 2018
Publication statusPublished - 19 Jan 2019

Bibliographical note

The start-up phase of the FOCUS trial was funded by the UK Stroke Association (TSA 2011101) and the main phase funded by the NIHR Health Technology Assessment Programme (project number 13/04/30). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the NIHR Health Technology Assessment Programme. Recruitment and follow-up was supported by the NIHR-funded UK Stroke Research Network and the Scottish Stroke Research Network, which was supported by NHS Research Scotland (NRS).

The study protocol and statistical analysis plan have been published.5, 6 A fully anonymised trial dataset with individual participant data and a data dictionary will be made available to other researchers after the publication of the full trial report in the Health Technology Assessment journal in 2019. Requests should first be directed to Martin Dennis (Co-Chief Investigator). Written proposals will be assessed by the FOCUS trial team and a decision made about the appropriateness of the use of data. A data sharing agreement will be put in place before any data will be shared.


  • Administration, Oral
  • Aged
  • Antidepressive Agents, Second-Generation/administration & dosage
  • Depression/epidemiology
  • Double-Blind Method
  • Female
  • Fluoxetine/administration & dosage
  • Fractures, Bone/chemically induced
  • Humans
  • Male
  • Middle Aged
  • Recovery of Function
  • Stroke Rehabilitation/methods
  • Surveys and Questionnaires


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