{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:52:58Z","timestamp":1790823178153,"version":"4.1.0"},"reference-count":97,"publisher":"National Institute for Health and Care Research","issue":"22","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["13\/04\/30"],"award-info":[{"award-number":["13\/04\/30"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000364","name":"Stroke Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title><jats:p>Our Cochrane review of selective serotonin inhibitors for stroke recovery indicated that fluoxetine may improve functional recovery, but the trials were small and most were at high risk of bias.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objectives<\/jats:title><jats:p>The Fluoxetine Or Control Under Supervision (FOCUS) trial tested the hypothesis that fluoxetine improves recovery after stroke.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title><jats:p>The FOCUS trial was a pragmatic, multicentre, parallel-group, individually randomised, placebo-controlled trial.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title><jats:p>This trial took place in 103 UK hospitals.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title><jats:p>Patients were eligible if they were aged \u2265\u200918 years, had a clinical stroke diagnosis, with focal neurological deficits, between 2 and 15 days after onset.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title><jats:p>Patients were randomly allocated 20\u2009mg of fluoxetine once per day or the matching placebo for 6 months via a web-based system using a minimisation algorithm.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Main outcome measures<\/jats:title><jats:p>The primary outcome was the modified Rankin Scale at 6 months. Patients, carers, health-care staff and the trial team were masked to treatment allocation. Outcome was assessed at 6 and 12 months after randomisation. Patients were analysed by their treatment allocation as specified in a published statistical analysis plan.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title><jats:p>Between 10 September 2012 and 31 March 2017, we recruited 3127 patients, 1564 of whom were allocated fluoxetine and 1563 of whom were allocated placebo. The modified Rankin Scale score at 6 months was available for 1553 out of 1564 (99.3%) of those allocated fluoxetine and 1553 out of 1563 (99.4%) of those allocated placebo. The distribution across modified Rankin Scale categories at 6 months was similar in the two groups (common odds ratio adjusted for minimisation variables 0.951, 95% confidence interval 0.839 to 1.079;<jats:italic>p<\/jats:italic>\u2009=\u20090.439). Compared with placebo, patients who were allocated fluoxetine were less likely to develop a new episode of depression by 6 months [210 (13.0%) vs. 269 (16.9%), difference \u20133.78%, 95% confidence interval \u20131.26% to \u20136.30%;<jats:italic>p<\/jats:italic>\u2009=\u20090.003], but had more bone fractures [45 (2.9%) vs. 23 (1.5%), difference 1.41%, 95% confidence interval 0.38% to 2.43%;<jats:italic>p<\/jats:italic>\u2009=\u20090.007]. There were no statistically significant differences in any other recorded events at 6 or 12 months. Health economic analyses showed no differences between groups in health-related quality of life, hospital bed usage or health-care costs.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Limitations<\/jats:title><jats:p>Some non-adherence to trial medication, lack of face-to-face assessment of neurological status at follow-up and lack of formal psychiatric diagnosis during follow-up.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Conclusions<\/jats:title><jats:p>20\u2009mg of fluoxetine daily for 6 months after acute stroke did not improve patients\u2019 functional outcome but decreased the occurrence of depression and increased the risk of fractures. These data inform decisions about using fluoxetine after stroke to improve functional outcome or to prevent or treat mood disorders. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) (Australasia\/Vietnam) and Efficacy oF Fluoxetine \u2013 a randomisEd Controlled Trial in Stroke (EFFECTS) (Sweden) trials recruited an additional 2780 patients and will report their results in 2020. These three trials have an almost identical protocol, which was collaboratively developed. Our planned individual patient data meta-analysis will provide more precise estimates of the effects of fluoxetine after stroke and indicate whether or not effects vary depending on patients\u2019 characteristics and health-care setting.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Trial registration<\/jats:title><jats:p>Current Controlled Trials ISRCTN83290762.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-12\"><jats:title>Funding<\/jats:title><jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in<jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 24, No. 22. See the NIHR Journals Library website for further project information. The Stroke Association (reference TSA 2011101) funded the start-up phase.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta24220","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T11:55:31Z","timestamp":1590494131000},"page":"1-94","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Fluoxetine to improve functional outcomes in patients after acute stroke: the FOCUS RCT"],"prefix":"10.3310","volume":"24","clinical-trial-number":[{"clinical-trial-number":"isrctn83290762","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-8972","authenticated-orcid":true,"given":"Martin","family":"Dennis","sequence":"first","affiliation":[{"name":"Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-7328","authenticated-orcid":true,"given":"Graeme J","family":"Hankey","sequence":"additional","affiliation":[{"name":"Medical School, University of Western Australia, Crawley, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-8026","authenticated-orcid":true,"given":"Allan","family":"House","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1210-2314","authenticated-orcid":true,"given":"Stephanie","family":"Lewis","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, 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