TY - JOUR
T1 - Effects of fluoxetine on functional outcomes after acute stroke (FOCUS)
T2 - a pragmatic, double-blind, randomised, controlled trial
AU - FOCUS Trial Collaboration
AU - Dennis, Martin
AU - Mead, Gillian
AU - Forbes, John
AU - Graham, Catriona
AU - Hackett, Maree
AU - Hankey, Graeme J.
AU - House, Allan
AU - Lewis, Stephanie
AU - Lundström, Erik
AU - Sandercock, Peter
AU - Innes, Karen
AU - Williams, Carol
AU - Drever, Jonathan
AU - Mcgrath, Aileen
AU - Deary, Ann
AU - Fraser, Ruth
AU - Anderson, Rosemary
AU - Walker, Pauli
AU - Perry, David
AU - Mcgill, Connor
AU - Buchanan, David
AU - Chun, Yvonne
AU - Dinsmore, Lynn
AU - Maschauer, Emma
AU - Barugh, Amanda
AU - Mikhail, Shadia
AU - Blair, Gordon
AU - Hoeritzauer, Ingrid
AU - Scott, Maggie
AU - Fraser, Greig
AU - Lawrence, Katherine
AU - Shaw, Alison
AU - Williamson, Judith
AU - Burgess, David
AU - Macleod, Malcolm
AU - Morales, Dan
AU - Sullivan, Frank
AU - Brady, Marian
AU - French, Ray
AU - Van Wijck, Frederike
AU - Watkins, Caroline
AU - Proudfoot, Fiona
AU - Skwarski, Joanna
AU - Mcgowan, Diane
AU - Murphy, Rachael
AU - Burgess, Seona
AU - Rutherford, William
AU - Mccormick, Katrina
AU - Blackburn, Ruth
AU - Williams, Sarah
N1 - Funding Information:
The protocol was approved by the Scotland A Multicentre Research Ethics Committee (Dec 21, 2011). The study was jointly sponsored by the University of Edinburgh and NHS Lothian. The full protocol is available in the appendix .
Funding Information:
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).
Publisher Copyright:
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
PY - 2019/1/19
Y1 - 2019/1/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060034267&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(18)32823-X
DO - 10.1016/S0140-6736(18)32823-X
M3 - Article
C2 - 30528472
AN - SCOPUS:85060034267
SN - 0140-6736
VL - 393
SP - 265
EP - 274
JO - The Lancet
JF - The Lancet
IS - 10168
ER -