Compared with placebo, treatment with fluoxetine following an acute stroke had no effect on functional outcomes at 12 months; patients who received fluoxetine scored lower in memory and communication at follow-up, according to study findings published in Stroke.
In a primary analysis, results of a clinical trial (Efficacy of Fluoxetine – A Randomised Controlled Trial in Stroke [EFFECTS]), showed that 20 mg of fluoxetine vs placebo once daily for 6 months following acute stroke did not improve functional outcomes.
The EFFECTS trial was a multicenter study conducted in Sweden that randomly assigned adult patients with stroke (mean age, 71 years) to receive either 20 mg oral fluoxetine (n=750) or placebo (n=750) orally daily for up to 6 months.
Researchers of the primary analysis noted that although fluoxetine reduced depression, it increased fractures and hyponatremia.
The current study sought to determine whether the effects seen at 6 months persisted at 12 months among this patient population.
In the secondary analysis, patients were followed up for another 6 months to determine functional outcomes using the modified Rankin scale (mRS). In addition, the researchers assessed quality of life, fatigue, mood, and depression at the 1-year follow-up. Health status was also assessed using the 59-item self-reported Stroke Impact Scale (SIS) questionnaire version 3.0.
Patients in the EFFECTS trial had received a clinical diagnosis of acute stroke within 2 to 15 days from study entry. The majority of patients had ischemic stroke (87.4%), while the remaining patients had either intracerebral hemorrhage (12.3%) or nonstroke (0.2%). The median duration of treatment for both groups was 180 days, with 89% of patients taking their assigned medication for at least 150 days.
At 1 year, data were available for 715 patients in the fluoxetine group (95%) and 712 patients in the placebo group (95%). There was no difference between the 2 groups with regard to the distribution of mRS categories at 12 months (adjusted common odds ratio, 0.92; 95% CI, 0.76-1.10).
In addition, there was no difference between the fluoxetine and placebo groups at 12 months in terms of median scores on assessments of fatigue (56 vs 56, respectively; P =.22), mental health (76 vs 76, respectively; P =.57), and health-related quality of life (0.74 vs 0.74, respectively; P =.86).
Despite these findings, patients who received fluoxetine vs those who received placebo demonstrated significantly worse values on the SIS domains for memory (median, 89 vs 93, respectively; P =.0021) and communication (median, 93 vs 96, respectively; P =.024). The researchers mentioned that these findings were “unexpected” and not supported by previous trials, suggesting the worsened memory and communication scores were caused by “chance” that was “due to random error associated with multiple analyses.”
Study limitations included the inclusion of only patients receiving care in the Swedish health care system, as well as the lack of assessment for the level and intensity of rehabilitation during follow-up.
The researchers concluded that “more precise estimates of any effects of fluoxetine will be available from our prospective meta-analysis of individual patient data from the FOCUS, AFFINITY and EFFECTS trials.”
Lundström E, Isaksson E, Greilert Norin N, et al. Effects of fluoxetine on outcomes at 12 months after acute stroke: Results from EFFECTS, a randomized controlled trial. Stroke. Published online August 31, 2021. doi:10.1161/STROKEAHA.121.034705