Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial

Erik Lundström, Eva Isaksson, Nora Greilert Norin, Per Näsman, Per Wester, Björn Mårtensson, Bo Norrving, Håkan Wallén, Jörgen Borg, Graeme J. Hankey, Maree L Hackett, Gillian Mead, Martin Dennis, Katharina Stibrant Sunnerhagen, EFFECTS Writing Committee

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

BACKGROUND AND PURPOSE
The Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke (EFFECTS) recently reported that 20 mg fluoxetine once daily for 6 months after acute stroke did not improve functional outcome but reduced depression and increased fractures and hyponatremia at 6
months. The purpose of this pre-defined secondary analysis was to identify if any effects of fluoxetine were maintained or delayed over 12 months.

METHODS
EFFECTS was an investigator-led, randomized, placebo-controlled, double-blind, parallel group trial in Sweden that enrolled adult stroke patients. Patients were randomized to 20 mg oral fluoxetine or matching placebo for 6 months and followed for another 6 months. The
primary outcome was functional outcome (modified Rankin scale, mRS), at 6 months. Predefined secondary outcomes for these analyses included the mRS, health status, quality of life, fatigue, mood and depression at 12 months.

RESULTS
1500 patients were recruited from 35 centers in Sweden between 2014 and 2019; 750 were allocated fluoxetine and 750 placebo. At 12 months, mRS data were available in 715 (95%) patients allocated fluoxetine and 712 (95%) placebo. The distribution of mRS categories was similar in the two groups (adjusted common odds ratio 0.92 [95% CI 0.76–1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (IQR 75–100) vs 93 (IQR 82–100); p=0.0021) and communication 93 (IQR 82–100) vs 96 (IQR 86–100); p=0.024) domains of the Stroke Impact Scale compared to placebo. There were no other
differences in secondary outcomes.

CONCLUSIONS
Fluoxetine after acute stroke had no effect on functional outcome at 12 months. Patients allocated fluoxetine scored worse on memory and communication on the Stroke Impact Scale compared to placebo, but this is likely to be due to chance.

CLINICAL TRIAL REGISTRATIONS
The EU Clinical Trials Register https://www.clinicaltrialsregister.eu/ctrsearch/search?query=2011-006130-16.
ClinicalTrials.gov NCT02683213. https://clinicaltrials.gov/ct2/show/NCT02683213.

Non-standard Abbreviations and Acronyms
AFFINITY Assessment oF FluoxetINe In sTroke recoverY trial
EFFECTS Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke
EQ-5D-5L The 5-level EQ-5D version
FLAME FLuoxetine for motor recovery After acute ischeMic strokE trial
FOCUS Fluoxetine Or Control Under Supervision trial
MHI-5 Mental Health Inventory-5
N06A The Anatomical Therapeutic Chemical (ATC) code for antidepressant drugs.
N06A includes N06AA, N06AB, N06AF, N06AG, and N06AX.
RCT Randomized controlled trial
SIS Stroke Impact Scale version 3.0
SSRI Selective serotonin re-uptake inhibitor
mRS Modified Rankin Scale
SF-36 36-Item Short Form Health Survey
Original languageEnglish
JournalStroke
Early online date31 Aug 2021
DOIs
Publication statusE-pub ahead of print - 31 Aug 2021

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