{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:09:17Z","timestamp":1777943357095,"version":"3.51.4"},"reference-count":19,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Stroke Association, National Institute of Health Research"},{"name":"Australian Government National Health and Medical Research Council"},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003793","name":"Swedish Heart-Lung Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003792","name":"Swedish Brain Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007687","name":"Swedish Society of Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"crossref"}]},{"name":"King Gustav V and Queen Victoria's Foundation of Freemasons and STROKE-Riksf\u00f6rbundet"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Stroke"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Observational studies have shown that selective serotonin reuptake inhibitors are associated with an increased risk of bone fractures, but the association can be confounded by indication and other sources of systematic bias that can be minimized in randomized controlled trials (RCTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>Our aim was to report the rate, site, context, and predictors of fractures after stroke, and whether the fractures modified the effect of fluoxetine on modified Rankin scale (mRS) at 6\u2009months in an individual patient data meta-analysis of 5907 patients enrolled in three RCTs of fluoxetine (20\u2009mg for 6\u2009months) for stroke recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We classified fractures by treatment allocation, site (and thus likelihood of osteoporosis), and context, then performed multivariable analyses to explore the independent predictors of fractures. We explored whether the trend toward a poorer mRS at 6\u2009months was explained by a fracture excess. Risk of bias was assessed using GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among 5907 patients randomized at a mean of 6.6\u2009days (SD 3.6) post-stroke onset and followed for 6\u2009months, the number of fractures at 6\u2009months was 93 (3.15%) in the fluoxetine group versus 41 (1.39%) in the control group (difference 1.76, 95% CI 0.10\u20132.51). However, 128 patients with fractures were suitable for further analyses. Of these, 102 (80%) were in sites typically affected by osteoporosis; 115 (90%) were associated with falls and 1 (1%) with a seizure. Independent fracture risk factors were female sex (hazard ratio (HR) 1.96; 95% CI 1.37\u20132.81, p\u2009=\u20090.0002), age\u2009&gt;\u200970\u2009years (HR 2.30, 95% CI 1.52\u20133.49, p\u2009&lt;\u20090.001), previous fractures (HR 0.63 for no previous fractures, 95% CI 0.42\u20130.94, p\u2009=\u20090.0227), and randomized treatment (fluoxetine) (HR 2.39; 95% CI 1.64\u20133.49, p\u2009&lt;\u20090.001). The common odds ratio for the effect of fluoxetine on mRS at 6\u2009months was unchanged after excluding fracture patients. Risk of bias was high for imprecision.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Fractures were more common in the fluoxetine group but the absolute risk of fractures was small and risk estimates were imprecise. Most fractures occurred with a fall, and in osteoporotic locations. Fractures did not modify the effect of fluoxetine on functional outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17474930251316164","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:27:27Z","timestamp":1737347247000},"page":"540-549","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Fluoxetine and fractures after stroke: An individual patient data meta-analysis of three large randomized controlled trials of fluoxetine for stroke recovery"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-2023","authenticated-orcid":false,"given":"Gillian","family":"Mead","sequence":"first","affiliation":[{"name":"Usher Institute, The University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catriona","family":"Graham","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Research Facility, Western General Hospital, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5313-9052","authenticated-orcid":false,"given":"Erik","family":"Lundstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Neurology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-7328","authenticated-orcid":false,"given":"Graeme J","family":"Hankey","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular and Neurological Disorders, Medical School, The University of Western Australia, Perth, WA, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Perth, WA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1211-9087","authenticated-orcid":false,"given":"Maree L","family":"Hackett","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Barangaroo, NSW, Australia"},{"name":"Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia"},{"name":"University of Central Lancashire, Lancashire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4975-9793","authenticated-orcid":false,"given":"Laurent","family":"Billot","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"N\u00e4sman","sequence":"additional","affiliation":[{"name":"KTH Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Forbes","sequence":"additional","affiliation":[{"name":"University of Limerick, Limerick, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Dennis","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.043094"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcm067"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare10050803"},{"key":"e_1_3_3_5_2","article-title":"Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery","volume":"11","author":"Legg LA","year":"2021","unstructured":"Legg LA, Rudberg AS, Hua X, et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev 2021; 11: CD009286.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32823-X"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30207-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30219-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-017-2385-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/17474930241242628"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.026639"},{"key":"e_1_3_3_12_2","unstructured":"Higgins JPT Savovi\u0107 J Page MJ et al. Chapter 8: Assessing risk of bias in a randomized trial [last updated October 2019]. In: Higgins JPT Thomas J Chandler J et al. (editors). Cochrane handbook for systematic reviews of interventions (version 6.5). 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