A recent clinical trial indicates that fluvoxamine, a common antidepressant, may significantly reduce fatigue in long COVID patients, improving their quality of life.
New Delhi, India Jul 19, 2026 ALN: 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. This finding is particularly significant given the ongoing impact of the COVID-19 pandemic, which has left millions grappling with long-term issues, including long COVID, a condition characterized by a range of symptoms that persist long after the initial infection has resolved.
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 peer-reviewed medical journal that focuses on internal medicine and related fields.
Fatigue is among the most frequent and disabling symptoms reported by people with long COVID. For many individuals, the exhaustion is severe enough to interfere with employment, family responsibilities, and everyday activities. This debilitating fatigue can be accompanied by other symptoms such as brain fog, muscle pain, and sleep disturbances, making it a multifaceted issue that complicates recovery. Despite the scale of the problem, there are still few treatments supported by strong clinical evidence, leaving many patients in a state of uncertainty and distress.
"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 Research Methods, Evidence, and Impact, and co-principal investigator of the trial. Mills emphasized the importance of providing patients with reliable treatment options, especially as the pandemic has highlighted the limitations of current medical responses to long COVID. "Fluvoxamine showed consistent and meaningful benefits, and because it's already widely used and well understood, it has clear potential for clinical use," he added.
Researchers from Canada, Brazil, and the United States jointly led the study, demonstrating an international collaboration aimed at addressing a pressing crisis. Clinical sites were located in Belo Horizonte and throughout Minas Gerais, Brazil, indicating a focused effort to gather diverse data from a population that has been significantly affected by the pandemic.
The REVIVE-TOGETHER trial brought together investigators from prestigious institutions, including McMaster University, the University of British Columbia, Stanford University, the University of Pittsburgh, Duke University, Georgetown University, and several Brazilian institutions. This collaboration underscores the global nature of the long COVID challenge and the need for coordinated research efforts.
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, metformin (a common diabetes medication), or a placebo for 60 days. This design allowed researchers to rigorously assess the efficacy of these medications in alleviating long COVID symptoms.
"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. The rationale for selecting fluvoxamine and metformin stems from their known effects on inflammation and metabolic processes, which are thought to play a role in the pathophysiology of long COVID.
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, suggesting that the medication not only alleviated fatigue but also contributed to an improved sense of well-being.
In contrast, 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. However, in this trial, the drug provided no meaningful improvement for people who already had established long COVID fatigue. This finding highlights the complexity of long COVID and the need for targeted treatments that address specific symptoms.
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 adaptive design is particularly beneficial in the context of urgent crises, where timely data can influence treatment protocols and patient care.
"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, who is also a part-time associate professor at McMaster, noted that this innovative approach not only enhances the efficiency of clinical trials but also ensures that patients receive effective treatments sooner.
Long COVID continues to pose a major global challenge and is estimated to affect about 65 million people worldwide. The condition encompasses a wide range of symptoms, including fatigue, respiratory issues, cognitive impairments, and psychological effects. Because proven therapies remain scarce, most medical recommendations focus on supportive strategies, including activity pacing and management of individual symptoms. This highlights the urgency for continued research and the development of targeted interventions.
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. The complexity of long COVID necessitates a multifaceted approach to treatment, which may include pharmacological interventions, rehabilitation programs, and psychological support.
"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 hope is that fluvoxamine can be integrated into treatment plans for individuals suffering from long COVID fatigue, providing them with a much-needed avenue for relief.
The research was funded by The Latona Foundation.
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