Common Antidepressant Relieves Long Covid Fatigue

A randomized clinical trial has found that fluvoxamine, a low-cost and widely available antidepressant, significantly reduces fatigue and improves the quality of life for adults suffering from long COVID. The findings, published March 31, 2026, in the Annals of Internal Medicine, provide one of the first evidence-based medication options for a symptom that has left millions of people unable to return to their normal lives.

Fatigue is identified as the most common and debilitating symptom of long COVID. For many affected individuals, this persistent exhaustion creates severe barriers to employment and the ability to care for family members.

Trial Design and Participant Criteria

The study was co-led by a global research team with contributors from the United States, Canada, and Brazil. Clinical sites for the trial were established in the city of Belo Horizonte and across Minas Gerais, Brazil.

The trial enrolled 399 adults in Brazil who had been experiencing long COVID symptoms for at least 90 days following a SARS-CoV-2 infection. To ensure the study targeted those with significant impairment, all participants were required to have a score of at least four points on the Fatigue Severity Scale.

The Fatigue Severity Scale is a validated seven-point measure used to rate levels of tiredness or exhaustion, with a score of seven representing the most severe fatigue.

Key Findings and Outcomes

The randomized, placebo-controlled trial measured the impact of fluvoxamine over a 60-day period. The researchers observed meaningful improvements in the group receiving the medication compared to those receiving a placebo.

After 30 days of treatment, participants assigned to take fluvoxamine were nearly 50% more likely than the placebo group to rate their fatigue at a score of three or less on the severity scale.

By the 60-day mark, the medication had lowered self-reported fatigue ratings by nearly half a point. Those taking fluvoxamine reported a better overall quality of life and experienced fewer adverse events than those in the placebo group.

The study also tested the efficacy of metformin, a diabetes medication known to help prevent long COVID. However, the researchers found that metformin did not alleviate fatigue more effectively than the placebo.

Expert Perspectives

Edward Mills, a professor in McMaster University’s Department of Health Research Methods, Evidence, and Impact and a co-principal investigator of the trial, highlighted the importance of these findings for patients seeking evidence-based treatment.

Fluvoxamine showed consistent and meaningful benefits, and because it’s already widely used and well understood, it has clear potential for clinical use.

Edward Mills

Jamie Forrest, PhD, MPH, who serves as the scientific director of the University of British Columbia’s Health Equity & Resilience Observatory and was a co-author of the study, noted that the primary objective of such research is to get people back to feeling normal. Regarding the performance of fluvoxamine, Forrest stated, I think fluvoxamine’s done great.

The Global Impact of Long COVID

Long COVID continues to be a significant public health challenge, with an estimated 65 million people affected worldwide years after the acute phase of the pandemic.

While fatigue is the most prevalent symptom, the condition manifests through a wide variety of other persistent issues. These include:

• Memory problems, commonly referred to as brain fog
• Heart palpitations
• Joint and muscle pain

Researchers suggest that the results of this trial indicate fluvoxamine is a viable option to try for those struggling with the debilitating fatigue associated with the condition.