Fluvoxamine shows efficacy in long-COVID fatigue
Researchers report that the antidepressant fluvoxamine has significantly reduced long COVID–related fatigue, and that the diabetes drug metformin has no such benefit.
“Patients taking fluvoxamine reported steadily improving fatigue and quality-of-life scores over 60 to 90 days, with fewer side effects than those on placebo, they said.
The findings were published on March 30,2026 in Annals of Internal Medicine.
The investigators enrolled 399 adults with fatigue persisting 90 or more days following a confirmed SARS-CoV-2 infection.
The trial was conducted in 22 outpatient medical sites in Brazil between October 2023 and February 2025.
The subjects were randomized to 60-day treatment with fluvoxamine (100 mg twice daily), metformin (750 mg twice daily) or matching placebo.
The study excluded people with diabetes, stroke, Lyme disease or other COVID-19 complications. It also excluded people identified as substance abusers, those with uncontrolled psychiatric conditions and those already being treated with fluvoxamine or metformin.
The primary outcome was the change between baseline and 60-day scores on the Fatigue Severity Scale (FSS), a 9-item self-reported measure of fatigue severity, with higher scores indicating worse fatigue.
The investigators reported that, at day 60, fluvoxamine subjects had achieved a significant reduction in fatigue compared with placebo subjects. And the effect was sustained at day 90.
Fluvoxamine treatment also improved quality-of-life scores, while metformin treatment showed no such benefit.
They reported that adverse events were less frequent with fluvoxamine (20.0%) than with metformin (28.8%) or placebo (29.7%).
The authors concluded, “This study supports the potential benefit of fluvoxamine in people with long COVID and fatigue lasting at least 90 days after acute COVID-19.”
