For millions of people still hurting months after COVID-19, the most popular advice has been to relax and wait. A new international study contradicts that approach, demonstrating that long-term COVID tiredness is a detectable biological condition that may be treated with an available, low-cost medication. 

The study, which was co-led by McMaster University and published on March 31, 2026, in the Annals of Internal Medicine, discovered that fluvoxamine, a commonly used antidepressant, dramatically reduced fatigue and increased quality of life in persons with protracted COVID. The findings are one of the first times a medicine has demonstrated clear benefit for this illness, which affects an estimated 65 million people globally. 

Fatigue from a long COVID is not the same as typical exhaustion. Many people describe it as a deep, continuous tiredness that makes even the most basic chores difficult. It has put many out of work and disrupted daily life. Due to a lack of established treatments, clinicians have primarily relied on supportive care, such as pacing activities. 

"This is an important step forward for patients who have been desperate for evidence-based options," says Edward Mills, the study's principal author and a McMaster University professor. "Fluvoxamine showed consistent and meaningful benefits, and because it's already widely used and well understood, it has clear potential for clinical use." 

The experiment included 399 adults in Brazil who had been suffering fatigue for at least 90 days following a confirmed COVID-19 infection. Participants were randomly assigned to either fluvoxamine, metformin, or a placebo for 60 days. A placebo is a dummy tablet that has no active substance and is used to determine if a real medicine works. 

The findings were remarkable. Fluvoxamine alleviated weariness more than placebo, with a 99 per cent probability that the improvement was due to the medicine rather than chance. Patients reported higher overall quality of life. 

Simply put, fluvoxamine is thought to function by restoring equilibrium in brain chemicals that influence how the body responds to stress and inflammation. Scientists believe that in extended COVID, this system may become "switched off" or disturbed, resulting in chronic weariness. The medicine could help turn it back on. 

"We wanted to test whether two existing, widely available, and affordable medications could help," Mills tells me. "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." 

While metformin has previously showed promise in lowering the risk of long-term COVID when given early in the infection, this study discovered that it did not provide considerable relief for individuals who were already fatigued. This contrast emphasises the importance of timing and targeted treatment. 

The trial also employed a contemporary technique called 'Bayesian adaptive design'. Simply said, this is a more efficient method of conducting clinical trials that enables researchers to obtain valid conclusions faster by changing the study as results arrive. 

"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," reports Gilmar Reis, the study's principal author. 

Experts warn that chronic COVID is a complex disorder with numerous symptoms, and one treatment may not be effective for everyone. However, the availability of a widely used and reasonably priced medicine provides a practical choice for clinicians and patients today. 

"This research provides clinicians with the first strong evidence that a drug can help minimise long-term COVID tiredness. Patients want something they can try right now, and this result takes us closer to that reality," says Jamie Forrest, the study's co-author. 

The findings suggest a shift in how long COVID can be treated—from treating symptoms to addressing underlying biological causes—giving new hope that recovery may no longer rely solely on rest.