Muhammad Rizwan Husain, MD

Lundström E, Isaksson E, Greilert Norin N, Näsman P, Wester P, Mårtensson B, Norrving B, Wallén H, Borg J, Hankey GJ, et al. Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial. Stroke. 2021.

The Efficacy oF Fluoxetine—a randomisEd Controlled Trial in Stroke (EFFECTS) was a randomized clinical trial whose primary outcome was to assess if oral fluoxetine initiated within 2-15 days of an acute stroke (ischemic or hemorrhagic) and taken up to 6 months improved functional outcomes. The initial trial results, which were published in August 2020, demonstrated no improvement in functional outcomes (modified Rankin Score-mRS-adjusted odds ratio: 0.94 [95% CI 0.78–1.13]) at 6 months with fluoxetine use and noted an increased rate of fractures and hyponatremia, though occurrence of depression was reduced (by 4%).

The authors now report 12-month follow-up results on outcomes that include the mRS, health status, quality of life, fatigue, mood and depression to see if any effects of fluoxetine persisted or were delayed.

At the 12-month follow-up, 87.4% had an ischemic stroke, 38.3% were women and median NIHSS was 3. No difference at 12 months was noted in the mRS categories (0 to 6) between fluoxetine and placebo (adjusted odds ratio 0.92 -95% CI 0.76–1.10). The authors also noted on the Stroke Impact Scale that patients on fluoxetine did poorly in domains of memory (89 vs 93; p=0.0021) and communication (93 vs 96; P=0.024). No other differences were noted in the rest of the secondary outcomes, such as fatigue, mood or health-related quality of life or depression.

Some limitations prudent to mention are that patients were monitored at the 6- and then 12-month mark and not in between, so data for safety and any intensive rehabilitation during this period are unknown. Depression was defined as those on an antidepressant at the 12-month mark, so this excludes patients who might have discontinued it at the 11-month mark and would not be accounted for. No clinical (face-face) evaluation of depression was done at the 12-month follow-up period. Most patients had mild strokes (median NIHSS 3), so it is unclear how this would correlate to a cohort with more severe strokes. The study continues to follow patients up to 3 years to evaluate for depression, fractures and seizures. 

To summarize, fluoxetine taken up to 6 months after stroke did not demonstrate any positive effect on functional outcomes at 12 months.