A major international clinical trial co-led by McMaster University found that the antidepressant fluvoxamine significantly reduced fatigue and improved quality of life for adults with long COVID, according to a March 30 announcement. The findings were published in the Annals of Internal Medicine.
Fatigue is reported as the most common and disabling symptom of long COVID, affecting millions globally and often preventing people from working or resuming normal activities. Few proven treatments exist for this condition.
Edward Mills, senior author and professor at McMaster's Department of Health Research Methods, Evidence, and Impact, said, "This is an important step forward for patients who have been desperate for evidence-based options. Fluvoxamine showed consistent and meaningful benefits, and because it's already widely used and well understood, it has clear potential for clinical use."
The study was conducted by a global team including researchers from Canada, Brazil, and the United States. Clinical sites were located in Belo Horizonte city and across Minas Gerais state in Brazil. The REVIVE-TOGETHER trial enrolled 399 adults who experienced fatigue at least 90 days after confirmed SARS-CoV-2 infection. Participants received either fluvoxamine (brand name: Luvox), metformin (a diabetes medication), or placebo over a period of 60 days.
Mills said the research aimed to test "whether two existing, widely available, and affordable medications could help" with long COVID fatigue since neither had previously been rigorously tested for this purpose.
Results showed that fluvoxamine reduced fatigue more than placebo with a high probability—99 percent—that it outperformed placebo. The drug also improved overall quality of life on several measures. In contrast to previous studies showing metformin can reduce risk if taken during acute infection phase, this trial found no significant benefit from metformin once long COVID symptoms are established.
Gilmar Reis of Cardresearch in Belo Horizonte described the methodology: "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." Reis is also part-time associate professor at McMaster University.
Despite an estimated 65 million people affected worldwide by long COVID—with most medical guidelines currently offering only supportive care—the researchers caution that while fluvoxamine appears promising for managing fatigue specifically, further studies are needed to understand which patients benefit most and how best to use such treatments alongside others under development.
Jamie Forrest from University of British Columbia concluded: "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." Funding was provided by The Latona Foundation.
