Fluvoxamine reduces fatigue in long COVID patients, global trial finds

A widely available, low-cost antidepressant significantly eased fatigue and improved quality of life for adults with long COVID in a randomized, placebo-controlled trial, according to findings published in the Annals of Internal Medicine.

The REVIVE-TOGETHER trial enrolled 399 adults in Brazil who had experienced ongoing fatigue for at least 90 days after confirmed SARS-CoV-2 infection. Participants were randomly assigned to receive fluvoxamine (100 mg twice daily), the diabetes drug metformin (750 mg twice daily), or matching placebo for 60 days. The study used a Bayesian adaptive design that allowed treatment arms to stop early once evidence became clear, as detailed in the McMaster University summary of the work (healthsci.mcmaster.ca).

Fluvoxamine outperformed placebo in reducing fatigue. Researchers reported a 99 percent probability that the drug was more effective than placebo. On the Fatigue Severity Scale, fluvoxamine produced a mean difference of -0.43 points at day 60 versus placebo, with the effect sustained at day 90 (mean difference -0.58), according to coverage of the trial data (empr.com). Participants on fluvoxamine also showed gains in quality-of-life measures and experienced fewer adverse events (20 percent) than those on metformin (28.8 percent) or placebo (29.7 percent).

After 30 days, people taking fluvoxamine were nearly 50 percent more likely than those on placebo to rate their fatigue as three or less on the seven-point scale; the relative advantage was 36 percent at 60 days and 19 percent at 90 days (30 days after stopping treatment), reported CIDRAP (cidrap.umn.edu). Metformin provided no meaningful improvement for established long COVID fatigue, despite earlier evidence that it can lower the risk of developing long COVID when used during acute infection.

The international team was co-led by researchers from McMaster University, the University of British Columbia, and institutions in Brazil and the United States, including Stanford, Pittsburgh, Duke, and Georgetown. Clinical sites were in Belo Horizonte and across Minas Gerais, Brazil. Senior author Edward Mills of McMaster University stated that fluvoxamine “showed consistent and meaningful benefits, and because it’s already widely used and well understood, it has clear potential for clinical use,” according to the university release (healthsci.mcmaster.ca) and ScienceDaily summary (sciencedaily.com).

Fatigue is among the most common and disabling symptoms of long COVID, which is estimated to affect about 65 million people worldwide. Proven pharmacological treatments remain scarce, with most guidance limited to supportive care such as pacing. Fluvoxamine, an SSRI typically used for obsessive-compulsive disorder and sold as Luvox or generic, has previously shown anti-inflammatory effects and reduced hospitalization risk in acute COVID-19. Researchers cautioned that it is not a complete solution for the multi-symptom condition and that further studies are needed to identify who benefits most, clarify mechanisms, and test combinations with other therapies.

Corresponding author Jamie Forrest of the University of British Columbia noted the trial provides “clinicians their first strong evidence for a medication that helps reduce long COVID fatigue.” Independent experts have described the benefit as potentially modest and called for replication in broader populations, as noted in Reuters Health Rounds coverage (reuters.com).

The research was funded by The Latona Foundation. Results were first reported around the March 31, 2026, publication date and later amplified by specialist outlets.

Why this is uncovered

The trial and findings were covered promptly by university releases, specialist health sites including CIDRAP, HealthDay/MPR, News-Medical, Respiratory Therapy, and ScienceDaily, plus a brief item in Reuters Health Rounds. Full-length reporting in major mainstream newspapers or broadcast outlets has been limited.