FOCUS trial - Fluoxetine Or Control Under Supervision (2019)

The FOCUS trial was a randomised controlled trial that aimed to find out whether fluoxetine given to people for six months after a stroke improves long-term recovery, even if they do not have depression.

3127 participants were recruited from 103 hospitals across the UK. The results did not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.

Trial dates

2012-2019

Trial team

FOCUS was led by Prof Martin Dennis and Prof Gillian Mead, with collaborators from:

University of Edinburgh
National Health Service
The UK Stroke research network including their user group
The Scottish Stroke Research Network
University of Dundee
University of Leeds
The George Institute, New South Wales
University of Western Australia
Karolinska Institute, Stockholm

FOCUS trial collaborators (608.41 KB PDF)

Study summary & findings

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

FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial of 3127 patients 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. Functional status, measured with the modified Rankin Scale (mRS), was assessed at 6 months and 12 months after randomisation.

Fluoxetine did not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. The results did not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.

FOCUS study summary (v1.4, May 2012) (26.48 KB PDF)

FOCUS trial full protocol (857.4 KB PDF)

ISRCTN registry: ISRCTN83290762

Publications

1: Dennis M, Forbes J, Graham C, Hackett M, Hankey GJ, House A, Lewis S, Lundström E, Sandercock P, Mead G. Fluoxetine to improve functional outcomes in patients after acute stroke: the FOCUS RCT. Health Technol Assess. 2020 May;24(22):1-94. doi: 10.3310/hta24220.

2: Dennis M, Forbes J, Graham C, Hackett ML, Hankey GJ, House A, Lewis S, Lundström E, Sandercock P, Mead G. Fluoxetine and Fractures After Stroke: Exploratory Analyses From the FOCUS Trial. Stroke. 2019 Nov;50(11):3280-3282. doi: 10.1161/STROKEAHA.119.026639. Epub 2019 Aug 20.

3: FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2019 Jan 19;393(10168):265-274. doi: 10.1016/S0140-6736(18)32823-X. Epub 2018 Dec 5.

4: Graham C, Lewis S, Forbes J, Mead G, Hackett ML, Hankey GJ, Gommans J, Nguyen HT, Lundström E, Isaksson E, Näsman P, Rudberg AS, Dennis M. The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis. Trials. 2017 Dec 28;18(1):627. doi: 10.1186/s13063-017-2385-6.

5: Mead G, Hackett ML, Lundström E, Murray V, Hankey GJ, Dennis M. The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: a study protocol for three multicentre randomised controlled trials. Trials. 2015 Aug 20;16:369. doi: 10.1186/s13063-015-0864-1.

Funding

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).

Related trials

EFFECTS (Sweden)

Functional outcome after acute stroke did not improve with oral fluoxetine 20 mg once daily for 6 months. Fluoxetine reduced the occurrence of depression but increased the risk of bone fractures and hyponatraemia.

EFFECTS Trial Collaboration. Safety and efficacy of fluoxetine on functional recovery after acute stroke (EFFECTS): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020 Aug;19(8):661-669. doi: 10.1016/S1474-4422(20)30219-2.

AFFINITY (Australia, New Zealand & Vietnam)

Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures.

AFFINITY Trial Collaboration. Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020 Aug;19(8):651-660. doi: 10.1016/S1474-4422(20)30207-6.

This article was published on 30 Nov, 2021