Common antidepressant shows promise in easing Long COVID fatigue
New study suggests fluvoxamine significantly reduces symptoms of fatigue and improves quality of life in Long COVID sufferers.
- 31 March 2026
- 4 min read
- by Priya Joi
At a glance
- A randomised trial found that fluvoxamine, a common antidepressant, reduced fatigue and improved quality of life in adults with Long COVID, while metformin (a diabetes drug) showed no benefit.
- The study enrolled 399 adults in Brazil with Long COVID with symptoms lasting at least 90 days after SARS-CoV-2 infection.
- Researchers say the findings offer one of the first robust signals for a treatment targeting one of Long COVID’s most disabling symptoms.
Years after the acute phase of the pandemic, Long COVID continues to affect an estimated 65 million people worldwide.
For many, the defining symptom is not respiratory illness, but persistent, debilitating fatigue that can make everyday life difficult to sustain.
Now, a randomised trial suggests that fluvoxamine, a widely used and inexpensive antidepressant, may help ease that burden.
In a study published in Annals of Internal Medicine, researchers reported that fluvoxamine significantly reduced fatigue in adults with Long COVID compared with a placebo, and improved their quality of life.
Fluvoxamine has piqued the interest of Long COVID researchers before. In 2020, a randomised trial published in JAMA found that the drug reduced clinical deterioration in outpatients with COVID-19.
Since then, fluvoxamine has also been proposed as a potential candidate treatment for neurocognitive symptoms of Long COVID such as brain fog, although robust trial evidence has been limited.
The new findings mark one of the first strong pieces of clinical trial evidence for a drug targeting Long COVID.
Antidepressant vs. anti-diabetic
The new study, known as the REVIVE-TOGETHER trial, enrolled 399 adults in Brazil who had experienced fatigue for at least 90 days after confirmed SARS-CoV-2 infection.
Participants were randomly assigned to receive fluvoxamine (a selective serotonin reuptake inhibitor or SSRI), metformin (a diabetes drug) or placebo for 60 days. The trial used an innovative adaptive design, allowing researchers to stop treatment arms early when results became clear.
Fluvoxamine showed a significant reduction in fatigue compared with placebo at day 60, measured using the Fatigue Severity Scale, with an estimated treatment effect of a reduction of 0.43 points, with a 99.0% probability that the drug outperformed placebo.
While the main outcome of the study was to look at any changes by 60 days, the researchers continued observing participants for another 30 days, and by day 90, the benefit from treatment was sustained, with an even larger estimated reduction of symptoms of 0.58 points.
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Patients receiving fluvoxamine also reported improvements in quality of life across multiple time points. Recovery, defined as a fatigue score below a specified threshold, was more frequent among those taking fluvoxamine than among those receiving placebo.
By contrast, metformin, which has shown promise in reducing the risk of developing Long COVID when taken during acute infection, did not demonstrate meaningful benefit for fatigue once the condition was established.
Chronic condition
Although Long COVID affects over 65 million people today, many of whom have had their lives upended by disability and an inability to function as they did before, treatment options remain limited.
Most clinical guidelines focus on supportive care, including pacing and symptom management, because so few treatments are proven enough for health systems to be willing to trial them.
This is in part, the researchers note, because Long COVID is a complex and heterogeneous condition, involving multiple biological pathways that may include immune dysregulation, persistent viral components and metabolic changes.
The persistent symptoms are linked to several mechanisms, including neuroinflammation, which fluvoxamine may be able to counteract, researchers have suggested previously.
However, in this current study, co-author Edward J Mills, at McMaster University, Canada, and colleagues say, “Rather than implying modification of underlying long COVID pathophysiology, the observed benefits may reflect improvements in overall well-being, symptom perception, or functional capacity.”
They point out that their trial did not assess biological correlates of response, such as inflammatory or metabolic biomarkers or self-reported measures of depression, which could have helped to elucidate mechanistic pathways.
Nevertheless, says Jamie Forrest, corresponding author and postdoctoral research fellow at the University of British Columbia, “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.”
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