Fluvoxamine Demonstrates Efficacy in Managing Long COVID Fatigue, Study Shows

A global clinical trial led by McMaster University has identified fluvoxamine, a commonly prescribed antidepressant, as a potential treatment for alleviating persistent fatigue associated with long COVID.

The randomized, placebo-controlled study, published in the Annals of Internal Medicine, demonstrated that fluvoxamine significantly reduced fatigue and enhanced quality of life among adults with post-COVID-19 condition. The medication, marketed under the brand name Luvox, is already approved for use in treating depression and other disorders.

Fatigue remains one of the most debilitating symptoms of long COVID, impairing daily functioning for many patients. Despite its prevalence, evidence-based treatments for this symptom are limited.

“This study represents a critical advancement for patients who have long sought clinically validated therapies,” states Edward Mills, the trial’s senior author and co-principal investigator. “Fluvoxamine’s rapid onset of action and established safety profile make it a promising candidate for immediate clinical application.”

The research collaboration spanned institutions in Canada, Brazil, and the United States, with clinical sites concentrated in Minas Gerais, Brazil.

The REVIVE-TOGETHER trial evaluated fluvoxamine alongside metformin and placebo in 399 Brazilian participants exhibiting fatigue lasting at least 90 days post-SARS-CoV-2 infection. Participants received one of the three interventions for 60 days.

According to Mills, the trial prioritized testing affordable, accessible medications with plausible biological mechanisms for alleviating long COVID symptoms. While fluvoxamine demonstrated statistically significant superiority over placebo (99% probability of effectiveness), metformin showed no meaningful benefit in this patient cohort.

The study employed a Bayesian adaptive trial design, enabling early termination of underperforming treatment arms once sufficient evidence emerged. This method accelerated conclusion-drawing while maintaining rigorous standards, as explained by co-lead author Gilmar Reis, a Brazilian researcher affiliated with McMaster and Cardresearch.

Long COVID affects an estimated 65 million people globally, with fatigue remaining inadequately addressed by current guidelines focused on symptom management. The research team emphasizes that fluvoxamine specifically targets fatigue rather than serving as a universal treatment for all long COVID manifestations.

“This trial provides the first robust clinical evidence for a medication effective against long COVID fatigue, offering a tangible option for clinicians and patients,” notes corresponding author Jamie Forrest, a University of British Columbia postdoctoral fellow. However, further research is needed to identify responders, explore drug mechanisms, and assess combination therapies.

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