Fluoxetine Does Not Decrease Symptoms of Clinical Depression in Patients After a Stroke

old man depression
old man depression
Researchers performed a secondary analysis of the AFFINITY trial that assessed the effects of fluoxetine treatment on depression symptoms in patients who recently had a stroke.

Among patients recovering from an ischemic or hemorrhagic stroke, treatment with fluoxetine vs placebo did not decrease symptoms of clinically significant depression, according to study findings published in JAMA Neurology.

The current study was a secondary analysis of the randomized, parallel-group, double-blind, placebo-controlled Assessment of Fluoxetine in Stroke Recovery (AFFINITY) trial. The study included 1221 patients enrolled in Australia, New Zealand, and Vietnam between 2013 and 2019 who had a recent stroke. Patients were randomly assigned 1:1 to receive either 6 months of treatment with oral fluoxetine 20 mg (n=614) or placebo (n=607). Symptoms of depression were assessed with the 9-item Patient Health Questionnaire (PHQ-9); clinically significant depression was defined as a PHQ-9 score of 9 or greater.

Patients included in the fluoxetine group had a mean age of 64.3±12.2 years; 62.3% were men; 85.1% had a history of ischemic stroke; 3.0% underwent prior treatment for depression; and 2.6% were currently receiving treatment for depression. Patients in the placebo group had a mean age of 63.4±12.4 years; 64.7% were men; 86.1% had a history of ischemic stroke; 4.9% had previously been treated for depression; and 2.4% were currently receiving treatment for depression.

Among patients in the fluoxetine and placebo groups, clinically significant decreases in depression symptoms were reported in 12.8% and 14.6% at 4 weeks, 10.8% and 9.7% at 12 weeks, and 7.0% and 8.2% at 26 weeks, respectively. Of patients who reported PHQ-9 scores of 9 or greater, 20.2% were in the fluoxetine group and 21.1% were in the placebo group.

Study findings indicated that among patients in both groups, symptoms of depression decreased with time (odds ratio [OR], 0.96; 95% CI, 0.80-1.27; P <.001), and that those treated with fluoxetine did not have significantly decreased symptoms of depression (OR, 1.01; 95% CI, 0.80-1.27; P =.94). In addition, the researchers did not observe a significant treatment-by-time interaction (OR range, 0.83-1.16; all P ³.34).

The factors that were found to have no significant association with depression outcomes included sex (P =.11), study site (P =.77), history of depression (P =.87), and stroke type (P =.94).

The study was limited by the inclusion of only patients with stable disease with mild to moderate cognitive deficits after sustaining a stroke. This limitation may have led to the relatively decreased prevalence of clinically significant depression reported during the trial.

Researchers concluded, “Current approaches to the prevention and management of clinically significant symptoms of depression after stroke require systematic assessment and attenuation of modifiable risk factors for depression, standardized diagnostic measures, and personalized interventions that are effective and safe rather than the routine prescription of antidepressants for all patients.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Almeida OP, Hankey GJ, Ford A, et al. Depression outcomes among patients treated with fluoxetine for stroke recovery: the AFFINITY randomized clinical trial. JAMA Neurol. Published online August 2, 2021. doi:10.1001/jamaneurol.2021.2418