Antidepressant Fluvoxamine Shows Promise Against Long COVID Fatigue in Major Trial

An inexpensive antidepressant already on pharmacy shelves worldwide could become one of the first proven treatments for long COVID fatigue, according to findings from a large international clinical trial coordinated by McMaster University.

The study, published in the Annals of Internal Medicine on July 18, 2026, tested fluvoxamine — marketed under the brand name Luvox and long prescribed for depression — in adults struggling with persistent exhaustion after COVID-19. Results showed that the drug significantly reduced fatigue and improved quality of life compared with a placebo, marking a rare breakthrough for a condition that has left millions without proven options.

A Global Effort to Address a Disabling Symptom

Fatigue ranks among the most frequent and debilitating symptoms associated with long COVID. For many patients, the exhaustion is severe enough to undermine employment, family responsibilities, and routine daily tasks. Yet despite the enormous scale of the problem — long COVID is estimated to affect roughly 65 million people globally — clinicians have had almost no evidence-based therapies to offer.

"This is an important step forward for patients who have been desperate for evidence-based options," said Edward Mills, senior author and professor in McMaster University's Department of Health Research Methods, Evidence, and Impact. "Fluvoxamine showed consistent and meaningful benefits, and because it's already widely used and well understood, it has clear potential for clinical use."

Known as the REVIVE-TOGETHER trial, the study united investigators from McMaster University, the University of British Columbia, Stanford University, the University of Pittsburgh, Duke University, Georgetown University, and multiple Brazilian institutions. All clinical sites were based in Belo Horizonte and the surrounding state of Minas Gerais, Brazil.

Testing Two Existing Medications

The trial enrolled 399 adults in Brazil who had been experiencing ongoing fatigue for at least 90 days following a confirmed SARS-CoV-2 infection. Participants were randomly assigned to one of three groups and received either fluvoxamine, metformin (a standard diabetes drug), or a placebo over a 60-day period.

"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," Mills noted.

Fluvoxamine clearly outperformed the placebo. Statistical analysis revealed a 99 percent probability that the drug was genuinely more effective at reducing fatigue. Participants taking fluvoxamine also reported gains in overall quality of life across multiple measures.

Metformin, by contrast, delivered no meaningful improvement. Earlier studies had suggested that taking metformin during acute COVID-19 infection might reduce the risk of later developing long COVID, but the drug showed no benefit for those already suffering from established long COVID fatigue.

An Innovative Trial Design

The research team employed a Bayesian adaptive trial design, a methodology that permits researchers to close individual treatment arms early once the data becomes sufficiently conclusive. This approach can generate reliable findings faster than a traditional trial design while preserving 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," said Gilmar Reis, lead author and researcher with Cardresearch, a Brazilian clinical research center based in Belo Horizonte. Reis also holds a part-time associate professorship at McMaster.

More Research Still Needed

The investigators stressed that fluvoxamine is not a cure-all for long COVID. The syndrome can involve numerous symptoms and biological pathways, and the medication appears specifically promising for managing fatigue rather than addressing the full spectrum of the condition.

Future studies will be needed to identify which patients are most likely to respond, to elucidate the mechanism by which the drug reduces fatigue, and to examine whether it might complement other treatments under development.

"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," said Jamie Forrest, corresponding author and postdoctoral research fellow at the University of British Columbia.

The research was funded by The Latona Foundation.

As long COVID continues to affect tens of millions of people worldwide, findings like these offer a glimmer of hope for patients and clinicians alike. If you found this article informative, consider sharing it with others who may benefit from learning about this breakthrough in long COVID treatment research.

Source: ScienceDaily