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Randomized Controlled Trial
. 2021 Sep 1;78(9):1072-1079.
doi: 10.1001/jamaneurol.2021.2418.

Depression Outcomes Among Patients Treated With Fluoxetine for Stroke Recovery: The AFFINITY Randomized Clinical Trial

Osvaldo P Almeida  1 , Graeme J Hankey  2 , Andrew Ford  1 , Christopher Etherton-Beer  2 , Leon Flicker  2 , Maree Hackett  3 ; Assessment of Fluoxetine in Stroke Recovery (AFFINITY) Trial Collaboration
Collaborators, Affiliations
Randomized Controlled Trial

Depression Outcomes Among Patients Treated With Fluoxetine for Stroke Recovery: The AFFINITY Randomized Clinical Trial

Osvaldo P Almeida et al. JAMA Neurol. .

Abstract

Importance: One in 3 adults experiences clinically significant symptoms of depression during the first year after a stroke, but evidence to support the use of antidepressants in this population remains scant.

Objective: To investigate whether daily treatment with 20 mg of fluoxetine hydrochloride reduces the proportion of people affected by clinically significant symptoms of depression after stroke.

Design, setting, and participants: In this secondary analysis of the Assessment of Fluoxetine in Stroke Recovery parallel-group, randomized (1:1 assignment), double-blind, placebo-controlled clinical trial, 1221 participants in Australia, New Zealand, and Vietnam were recruited between January 11, 2013, and June 30, 2019, and were followed up for 6 months. Adults aged 18 years or older were recruited 2 to 15 days after experiencing a stroke associated with modified Rankin Scale score of 1 or higher.

Interventions: Fluoxetine hydrochloride, 20 mg, or matched placebo daily for 26 weeks.

Main outcomes and measures: A 9-item Patient Health Questionnaire (PHQ-9) score of 9 or lower was a prespecified secondary outcome of the trial. Assessments were completed at baseline and at 4, 12, and 26 weeks. Other outcomes of interest included participant-reported clinician diagnosis of depression, prescription of a nontrial antidepressant, or nonpharmacologic treatment of depression. Analysis was on an intention-to-treat basis.

Results: A total of 607 participants (378 men [62.3%]; mean [SD] age, 64.3 [12.2] years) were randomly assigned treatment with placebo, and 614 participants (397 men [64.7%]; mean [SD] age, 63.4 [12.4] years) were randomly assigned treatment with 20 mg of fluoxetine hydrochloride daily. The groups were balanced for demographic and clinical measures. At baseline, 112 patients (18.5%) in the placebo group and 116 patients (18.9%) in the fluoxetine group had PHQ-9 scores of 9 or higher. During follow-up, 126 of 596 participants (21.1%) treated with placebo and 121 of 598 participants (20.2%) treated with fluoxetine had PHQ-9 scores of 9 or higher (P = .70). A similar proportion of participants with PHQ-9 scores less than 9 at baseline who were treated with fluoxetine hydrochloride and placebo developed PHQ-9 scores of 9 or higher during the trial (placebo, 72 of 488 [14.8%]; and fluoxetine, 63 of 485 [13.0%]; P = .43). A slightly higher number of participants in the placebo group than in the fluoxetine group had a participant-reported clinician diagnosis of depression (42 of 602 [7.0%] vs 26 of 601 [4.3%]; P = .05). By week 26, 14 participants (2.3%) in the placebo group and 12 participants (1.9%) in the fluoxetine group had died (P = .67).

Conclusions and relevance: Routine daily treatment with 20 mg of fluoxetine did not decrease the proportion of people affected by clinically significant symptoms of depression after a stroke, nor did it affect the proportion of people prescribed an antidepressant or receiving nonpharmacologic treatments compared with placebo.

Trial registration: http://anzctr.org.au Identifier: ACTRN12611000774921.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Almeida, Hankey, Ford, Etherton-Beer, Flicker, and Hackett reported receiving grants from National Health and Medical Research Council of Australia outside the submitted work. Dr Almeida reported receiving grants from National Health and Medical Research Council of Australia outside the submitted work. Dr Hankey reported receiving grants from the Swedish Research Council and the UK National Institute for Health Research and Technology, and personal fees from the American Heart Association outside the submitted work. Dr Flicker reported receiving grants from an Australian Medical Research Future Fund Next Generation Clinical Researchers Practitioner Fellowship outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow of Participants During the AFFINITY (Assessment of Fluoxetine in Stroke Recovery) Trial
PHQ indicates Patient Health Questionnaire.
Figure 2.
Figure 2.. Proportion of Participants With a 9-Item Patient Health Questionnaire (PHQ-9) Total Score of 9 or Higher During the Trial
Error bars indicate the SE of the proportions, darker colors indicate prevalent cases of depression, and lighter colors indicate new cases of depression.
See this image and copyright information in PMC

Comment in

References

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