Hamilton, ON, Apr 3: A global research team co-led by McMaster University has identified one of the first medications shown to significantly reduce fatigue in people living with Long COVID—marking a major breakthrough for millions affected by persistent post-pandemic symptoms.
The randomized, placebo-controlled clinical trial found that Fluvoxamine, a widely available and low-cost antidepressant, significantly improved fatigue levels and overall quality of life among adults with long COVID. The findings were published in Annals of Internal Medicine on March 31, 2026.
Fatigue remains the most common and debilitating symptom of long COVID, often preventing individuals from returning to work or normal daily activities. Despite its widespread impact, effective treatments have remained limited.
“This is an important step forward for patients who have been desperate for evidence-based options,” said Edward Mills, senior author of the study and professor at McMaster University. “Fluvoxamine showed consistent and meaningful benefits, and because it is already well understood, it has strong potential for clinical use.”
The REVIVE-TOGETHER trial enrolled 399 adults in Brazil who experienced fatigue for at least 90 days following a confirmed COVID-19 infection. Participants were randomly assigned to receive fluvoxamine, Metformin, or a placebo over a 60-day period.
Results showed a 99% probability that fluvoxamine outperformed placebo in reducing fatigue, along with measurable improvements in quality of life. In contrast, metformin—while previously shown to reduce the risk of developing long COVID—did not demonstrate meaningful benefits for treating established fatigue symptoms.
The study also utilized an advanced Bayesian adaptive trial design, allowing researchers to efficiently evaluate outcomes and discontinue less effective treatments early while maintaining scientific rigor.
“This innovative trial design enabled us to reach conclusions more quickly and effectively,” said Gilmar Reis, lead author and researcher at Cardresearch in Brazil.
Long COVID continues to pose a major global health challenge, affecting an estimated 65 million people worldwide. Current medical guidelines largely focus on symptom management due to the lack of proven therapies.
Researchers emphasize that while fluvoxamine represents a promising option, further studies are needed to determine which patients benefit most and how the treatment can be integrated with other emerging therapies.
“This trial gives clinicians their first strong evidence for a medication that helps reduce long COVID fatigue,” said Jamie Forrest of the University of British Columbia. “It brings us closer to offering patients a practical solution they can use today.”
The study was funded by the Latona Foundation.
