A widely available antidepressant may provide meaningful relief for people experiencing persistent fatigue from long COVID, according to a global clinical trial co-led by McMaster University.
Researchers found that fluvoxamine (sold under the brand name Luvox), an inexpensive medication already commonly used to treat depression and other conditions, reduced fatigue and improved quality of life in adults with long COVID. The randomized, placebo-controlled trial was published in the Annals of Internal Medicine.
A Potential Treatment for Long COVID Fatigue
Fatigue is among the most frequent and disabling symptoms reported by people with long COVID. For some, the exhaustion is severe enough to interfere with employment, family responsibilities, and everyday activities. Despite the scale of the problem, there are still few treatments supported by strong clinical evidence.
“This is an important step forward for patients who have been desperate for evidence-based options,” says Edward Mills, senior author, professor in McMaster’s Department of Health Research Methods, Evidence, and Impact, and co-principal investigator of the trial. “Fluvoxamine showed consistent and meaningful benefits, and because it’s already widely used and well understood, it has clear potential for clinical use.”
Researchers from Canada, Brazil, and the United States jointly led the study. Clinical sites were located in Belo Horizonte and throughout Minas Gerais, Brazil.
The REVIVE-TOGETHER trial brought together investigators from McMaster University, the University of British Columbia, Stanford University, the University of Pittsburgh, Duke University, Georgetown University, and several Brazilian institutions.
Testing Fluvoxamine and Metformin
The trial included 399 adults in Brazil who had experienced ongoing fatigue for at least 90 days after a confirmed SARS-CoV-2 infection. Participants were randomly placed into one of three groups and received fluvoxamine (sold under the brand name Luvox), metformin (a common diabetes medication), or a placebo for 60 days.
“We wanted to test whether two existing, widely available, and affordable medications could help. Both had biological reasons to think they might work against long COVID fatigue, but neither had been rigorously tested for this purpose in a proper clinical trial,” says Mills.
Fluvoxamine performed better than the placebo in reducing fatigue. The statistical analysis indicated a 99 percent probability that the medication was more effective than the placebo. Participants who received fluvoxamine also reported gains in overall quality of life across several measures.
Metformin did not produce the same results. Earlier research found that taking metformin during the initial stage of a COVID infection could lower the risk of later developing long COVID. In this trial, however, the drug provided no meaningful improvement for people who already had established long COVID fatigue.
An Adaptive Clinical Trial Design
Researchers used a Bayesian adaptive trial design, which allowed them to end individual treatment groups early once the evidence became sufficiently clear. This approach can produce reliable conclusions more quickly than a conventional trial while maintaining scientific rigor.
“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,” says Gilmar Reis, lead author, researcher with Cardresearch, a Brazilian clinical research center based in Belo Horizonte. Reis is also a part-time associate professor at McMaster.
More Research Is Still Needed
Long COVID continues to pose a major global health challenge and is estimated to affect about 65 million people worldwide. Because proven therapies remain scarce, most medical recommendations focus on supportive strategies, including activity pacing and management of individual symptoms.
The researchers caution that fluvoxamine is not a complete solution for long COVID. The condition can involve many different symptoms and biological processes, and the medication appears specifically promising for fatigue management.
Additional studies will be needed to determine which patients are most likely to benefit, understand why the drug works, and explore whether it could be used alongside other developing treatments.
“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,” says Jamie Forrest, corresponding author and postdoctoral research fellow at the University of British Columbia.
The research was funded by The Latona Foundation.