Antidepressant Eases Long COVID Fatigue, Study Shows

Fluvoxamine significantly improved fatigue and quality of life among adults with long COVID, researchers find.

Mar. 31, 2026 at 8:04am

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A global research team co-led by McMaster University has identified the antidepressant fluvoxamine as one of the first medications shown to meaningfully reduce fatigue in people living with long COVID. The randomized, placebo-controlled clinical trial found that fluvoxamine significantly improved fatigue and quality of life among adults with long COVID, offering a promising new treatment option for the millions still struggling with persistent symptoms years after the pandemic began.

Why it matters

Fatigue is the most common and debilitating symptom of long COVID, leaving many people unable to work, care for their families, or resume their normal lives. Despite its global impact, few proven treatments exist, so this finding represents an important step forward for patients who have been desperate for evidence-based options.

The details

The REVIVE-TOGETHER trial enrolled 399 adults in Brazil who continued to experience fatigue for at least 90 days after a confirmed SARS-CoV-2 infection. Participants were randomly assigned to receive fluvoxamine, metformin (a common diabetes medication), or a placebo for 60 days. The researchers found fluvoxamine reduced fatigue more than the placebo, with a 99% probability the drug outperformed the placebo. The medication also produced improvements in overall quality of life.

  • The findings were published on March 31, 2026 in the Annals of Internal Medicine.
  • The trial enrolled participants in the city of Belo Horizonte and across Minas Gerais, Brazil.

The players

McMaster University

A public research university in Hamilton, Ontario, Canada, and the co-lead institution for the REVIVE-TOGETHER trial.

Edward Mills

Senior author, professor in McMaster's Department of Health Research Methods, Evidence, and Impact, and co-principal investigator of the trial.

Gilmar Reis

Lead author, researcher with Cardresearch, a Brazilian clinical research center based in Belo Horizonte, and a part-time associate professor at McMaster.

Jamie Forrest

Corresponding author and postdoctoral research fellow at the University of British Columbia.

The Latona Foundation

The organization that funded the research.

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What they’re saying

“This is an important step forward for patients who have been desperate for evidence-based options. Fluvoxamine showed consistent and meaningful benefits, and because it's already widely used and well understood, it has clear potential for clinical use.”

— Edward Mills, Senior author, professor in McMaster's Department of Health Research Methods, Evidence, and Impact, and co-principal investigator of the trial

“The trial used a sophisticated adaptive design that allowed it to reach conclusions more efficiently than traditional trials, stopping early when the evidence was clear enough – a design innovation as important as the findings themselves.”

— Gilmar Reis, Lead author, researcher with Cardresearch, a Brazilian clinical research center based in Belo Horizonte, and a part-time associate professor at McMaster

“This trial gives clinicians their first strong evidence for a medication that helps reduce long COVID fatigue. Patients want something they can try today – and this finding brings us closer to that reality.”

— Jamie Forrest, Corresponding author and postdoctoral research fellow at the University of British Columbia

What’s next

Further studies are needed to understand who benefits most from fluvoxamine, how the medication works, and how it might be combined with other emerging treatments for the complex condition of long COVID.

The takeaway

This study provides the first strong evidence for a medication that can help reduce the debilitating fatigue experienced by millions of long COVID patients, offering a promising new treatment option that is already widely available and understood.