A widely available antidepressant may provide significant relief to people experiencing persistent fatigue due to 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 drug 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-term COVID fatigue
Fatigue is among the most common and disabling symptoms reported by people with long COVID. For some, burnout is severe enough to interfere with employment, family responsibilities, and daily activities. Despite the magnitude of the problem, there are still few treatments supported by solid 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 the Department of Health Research Methods, Evidence and Impact at McMaster and co-principal investigator of the trial. “Fluvoxamine showed consistent and significant benefits, and because it is 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 researchers from McMaster University, the University of British Columbia, Stanford University, the University of Pittsburgh, Duke University, Georgetown University and several Brazilian institutions.
Fluvoxamine and Metformin Test
The trial included 399 adults in Brazil who had experienced continuous 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 drugs 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 placebo in reducing fatigue. Statistical analysis indicated a 99 percent probability that the drug was more effective than the placebo. Participants receiving fluvoxamine also reported improvements in overall quality of life on several measures.
Metformin did not produce the same results. Previous research found that taking metformin during the early stage of a COVID infection could reduce the risk of developing long COVID in the future. However, in this trial, the drug did not provide any significant improvement for people who already had long COVID fatigue.
An adaptive clinical trial design
The researchers used an adaptive Bayesian 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 and researcher at 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 significant global health challenge, affecting an estimated 65 million people worldwide. Because proven therapies remain scarce, most medical recommendations focus on supportive strategies, including activity pacing and treatment of individual symptoms.
Researchers caution that fluvoxamine is not a complete solution for long COVID. The condition can involve many different symptoms and biological processes, and the drug specifically shows promise for managing fatigue.
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 treatments in development.
“This trial gives doctors their first solid evidence of a drug that helps reduce long-COVID fatigue. Patients want something they can try today, and this finding brings us closer to that reality,” said Jamie Forrest, corresponding author and postdoctoral researcher at the University of British Columbia.
The research was funded by the Latona Foundation.