Effects of fluoxetine on functional outcomes after acute stroke (FOCUS)

a pragmatic, double-blind, randomised, controlled trial

, Martin Dennis (Lead / Corresponding author), Gillian Mead, John Forbes, Catriona Graham, Maree Hackett, Graeme J. Hankey, Allan House, Stephanie Lewis, Erik Lundström, Peter Sandercock, Karen Innes, Carol Williams, Jonathan Drever, Aileen Mcgrath, Ann Deary, Ruth Fraser, Rosemary Anderson, Pauli Walker, David Perry & 32 others Connor Mcgill, David Buchanan, Yvonne Chun, Lynn Dinsmore, Emma Maschauer, Amanda Barugh, Shadia Mikhail, Gordon Blair, Ingrid Hoeritzauer, Maggie Scott, Greig Fraser, David Burgess, Daniel Morales, Frank Sullivan, Fiona Ross, Laura Burgess, Rachel Young, Maria Bokhari, David Bruce, Andrew Potter, Rachel Evans, Andrew Smith, Stuart Johnston, Sarah Ross, Mairi Stirling, Jennifer Simpson, Alison Wright, Syed Abid Raza, Angela Bell, Pradeep Kumar, Alastair Thompson, Muhammad Fozan Khan

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Abstract

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.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalThe Lancet
Volume393
Issue number10168
Early online date5 Dec 2018
DOIs
Publication statusPublished - 19 Jan 2019

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Fluoxetine
Randomized Controlled Trials
Stroke
Placebos
Bone Fractures
Recovery of Function
Therapeutics
Random Allocation
Caregivers
Registries
Odds Ratio
Delivery of Health Care

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Dennis, Martin ; Mead, Gillian ; Forbes, John ; Graham, Catriona ; Hackett, Maree ; Hankey, Graeme J. ; House, Allan ; Lewis, Stephanie ; Lundström, Erik ; Sandercock, Peter ; Innes, Karen ; Williams, Carol ; Drever, Jonathan ; Mcgrath, Aileen ; Deary, Ann ; Fraser, Ruth ; Anderson, Rosemary ; Walker, Pauli ; Perry, David ; Mcgill, Connor ; Buchanan, David ; Chun, Yvonne ; Dinsmore, Lynn ; Maschauer, Emma ; Barugh, Amanda ; Mikhail, Shadia ; Blair, Gordon ; Hoeritzauer, Ingrid ; Scott, Maggie ; Fraser, Greig ; Burgess, David ; Morales, Daniel ; Sullivan, Frank ; Ross, Fiona ; Burgess, Laura ; Young, Rachel ; Bokhari, Maria ; Bruce, David ; Potter, Andrew ; Evans, Rachel ; Smith, Andrew ; Johnston, Stuart ; Ross, Sarah ; Stirling, Mairi ; Simpson, Jennifer ; Wright, Alison ; Raza, Syed Abid ; Bell, Angela ; Kumar, Pradeep ; Thompson, Alastair ; Khan, Muhammad Fozan. / Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial. In: The Lancet. 2019 ; Vol. 393, No. 10168. pp. 265-274.
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title = "Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial",
abstract = "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.",
author = "Martin Dennis and Gillian Mead and John Forbes and Catriona Graham and Maree Hackett and Hankey, {Graeme J.} and Allan House and Stephanie Lewis and Erik Lundstr{\"o}m and Peter Sandercock and Karen Innes and Carol Williams and Jonathan Drever and Aileen Mcgrath and Ann Deary and Ruth Fraser and Rosemary Anderson and Pauli Walker and David Perry and Connor Mcgill and David Buchanan and Yvonne Chun and Lynn Dinsmore and Emma Maschauer and Amanda Barugh and Shadia Mikhail and Gordon Blair and Ingrid Hoeritzauer and Maggie Scott and Greig Fraser and David Burgess and Daniel Morales and Frank Sullivan and Fiona Ross and Laura Burgess and Rachel Young and Maria Bokhari and David Bruce and Andrew Potter and Rachel Evans and Andrew Smith and Stuart Johnston and Sarah Ross and Mairi Stirling and Jennifer Simpson and Alison Wright and Raza, {Syed Abid} and Angela Bell and Pradeep Kumar and Alastair Thompson and Khan, {Muhammad Fozan}",
note = "Funding: UK Stroke Association and NIHR Health Technology Assessment Programme.",
year = "2019",
month = "1",
day = "19",
doi = "10.1016/S0140-6736(18)32823-X",
language = "English",
volume = "393",
pages = "265--274",
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Dennis, M, Mead, G, Forbes, J, Graham, C, Hackett, M, Hankey, GJ, House, A, Lewis, S, Lundström, E, Sandercock, P, Innes, K, Williams, C, Drever, J, Mcgrath, A, Deary, A, Fraser, R, Anderson, R, Walker, P, Perry, D, Mcgill, C, Buchanan, D, Chun, Y, Dinsmore, L, Maschauer, E, Barugh, A, Mikhail, S, Blair, G, Hoeritzauer, I, Scott, M, Fraser, G, Burgess, D, Morales, D, Sullivan, F, Ross, F, Burgess, L, Young, R, Bokhari, M, Bruce, D, Potter, A, Evans, R, Smith, A, Johnston, S, Ross, S, Stirling, M, Simpson, J, Wright, A, Raza, SA, Bell, A, Kumar, P & Thompson, A & Khan, MF 2019, 'Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial', The Lancet, vol. 393, no. 10168, pp. 265-274. https://doi.org/10.1016/S0140-6736(18)32823-X

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial. /; Dennis, Martin (Lead / Corresponding author); Mead, Gillian; Forbes, John; Graham, Catriona; Hackett, Maree; Hankey, Graeme J.; House, Allan; Lewis, Stephanie; Lundström, Erik; Sandercock, Peter; Innes, Karen; Williams, Carol; Drever, Jonathan; Mcgrath, Aileen; Deary, Ann; Fraser, Ruth; Anderson, Rosemary; Walker, Pauli; Perry, David; Mcgill, Connor; Buchanan, David; Chun, Yvonne; Dinsmore, Lynn; Maschauer, Emma; Barugh, Amanda; Mikhail, Shadia; Blair, Gordon; Hoeritzauer, Ingrid; Scott, Maggie; Fraser, Greig; Burgess, David; Morales, Daniel; Sullivan, Frank; Ross, Fiona; Burgess, Laura; Young, Rachel; Bokhari, Maria; Bruce, David; Potter, Andrew; Evans, Rachel; Smith, Andrew; Johnston, Stuart; Ross, Sarah; Stirling, Mairi; Simpson, Jennifer; Wright, Alison; Raza, Syed Abid; Bell, Angela; Kumar, Pradeep; Thompson, Alastair; Khan, Muhammad Fozan.

In: The Lancet, Vol. 393, No. 10168, 19.01.2019, p. 265-274.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of fluoxetine on functional outcomes after acute stroke (FOCUS)

T2 - a pragmatic, double-blind, randomised, controlled trial

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 - Burgess, David

AU - Morales, Daniel

AU - Sullivan, Frank

AU - Ross, Fiona

AU - Burgess, Laura

AU - Young, Rachel

AU - Bokhari, Maria

AU - Bruce, David

AU - Potter, Andrew

AU - Evans, Rachel

AU - Smith, Andrew

AU - Johnston, Stuart

AU - Ross, Sarah

AU - Stirling, Mairi

AU - Simpson, Jennifer

AU - Wright, Alison

AU - Raza, Syed Abid

AU - Bell, Angela

AU - Kumar, Pradeep

AU - Thompson, Alastair

AU - Khan, Muhammad Fozan

N1 - Funding: UK Stroke Association and NIHR Health Technology Assessment Programme.

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.

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.

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

VL - 393

SP - 265

EP - 274

JO - Lancet

JF - Lancet

SN - 0140-6736

IS - 10168

ER -