Published in the Annals of Internal Medicine, the REVIVE-TOGETHER trial was co-led by McMaster University and involved researchers from Canada, Brazil, and the United States. The study included 399 adults in Brazil who had experienced persistent fatigue for at least 90 days after a confirmed SARS-CoV-2 infection. Participants were randomly assigned to receive fluvoxamine (brand name Luvox), metformin, or a placebo for 60 days.
Fluvoxamine performed significantly better than the placebo in reducing fatigue. The statistical analysis showed a 99 percent probability that the medication was more effective than placebo. Participants receiving fluvoxamine also reported gains in overall quality of life across multiple measures. Metformin, a common diabetes drug tested alongside fluvoxamine, did not produce meaningful improvement for established long COVID fatigue, though earlier research suggested it could reduce the risk of developing long COVID when taken during the initial infection.
The trial used a Bayesian adaptive design, which allowed researchers to stop individual treatment groups early once the evidence became clear. This approach produces reliable conclusions more efficiently than conventional trials. "The trial used a sophisticated adaptive design that allowed it to reach conclusions more efficiently than traditional trials," said lead author Dr. Gilmar Reis.
Long COVID is estimated to affect about 65 million people worldwide, with fatigue as the most common and disabling symptom. Despite the scale of the problem, few treatments have been supported by strong clinical evidence — until now. "This is an important step forward for patients who have been desperate for evidence-based options," said senior author Edward Mills of McMaster University. "Fluvoxamine showed consistent and meaningful benefits, and because it's already widely used and well understood, it has clear potential for clinical use."
The researchers caution that fluvoxamine is not a complete cure for long COVID, which can involve many different symptoms and biological processes. However, the medication appears specifically promising for fatigue management, offering a new tool for one of the condition's most challenging symptoms.
Knowledge takeaway: Fluvoxamine, a low-cost SSRI antidepressant, reduced long COVID fatigue in a 399-person randomized trial; the drug showed a 99% probability of being more effective than placebo; metformin did not help with established long COVID fatigue; long COVID affects roughly 65 million people globally; the study was published in the Annals of Internal Medicine and led by McMaster University.