Antidepressant May Reduce Fatigue in Long Covid Patients

A clinical trial has found that the antidepressant fluvoxamine can meaningfully reduce fatigue and improve the quality of life for adults suffering from long COVID. The findings, published in the Annals of Internal Medicine, offer a potential evidence-based treatment for one of the most debilitating and common symptoms of post-acute sequelae of SARS-CoV-2 (PASC).

Fatigue is estimated to affect 65 million people worldwide who are living with long COVID. For many, this exhaustion is severe enough to prevent them from working or performing daily care for their families, often persisting for years after the initial infection.

Clinical Trial Results and Methodology

The research involved an adaptive, randomized, placebo-controlled trial conducted at outpatient sites in Brazil. The study enrolled 399 adults who had experienced persistent fatigue for at least 90 days following a confirmed SARS-CoV-2 infection.

Participants were divided into three groups for a 60-day period: those receiving fluvoxamine at 100 mg twice daily, those receiving metformin (a diabetes medication) at 750 mg twice daily, and those receiving a placebo.

Researchers used the Fatigue Severity Scale, a validated seven-point measure where seven represents the worst level of exhaustion, to track primary outcomes. All participants in the study began with a fatigue score of at least four points.

After 30 days of treatment, participants taking fluvoxamine were nearly 50% more likely than the placebo group to report a fatigue rating of three or less. By the 60-day mark, fluvoxamine had lowered self-reported fatigue ratings by nearly half a point.

The study reported a mean difference in fatigue reduction compared to the placebo of -0.43 at day 60 and -0.58 at day 90. In contrast, metformin provided no significant benefit in alleviating fatigue.

Safety and Quality of Life

Beyond the reduction in fatigue, participants using fluvoxamine reported an improved overall quality of life. The medication also demonstrated a favorable safety profile compared to the other study groups.

Adverse events occurred in 20.0% of participants taking fluvoxamine, which was lower than the 28.8% seen in the metformin group and the 29.7% seen in the placebo group. Researchers noted that Grade 3 or higher adverse events were rare across all three trial groups.

What we have is an important step forward for patients who have been desperate for evidence-based options. Fluvoxamine showed consistent and meaningful benefits and has clear potential for clinical use.

Edward Mills, co-principal investigator and professor at McMaster University

Jamie Forrest, PhD, MPH, scientific director of the University of British Columbia’s Health Equity & Resilience Observatory and a study co-author, stated that the goal of the research is to get people back to feeling normal, adding, I think fluvoxamine’s done great.

Medical Context of Long COVID Fatigue

The neuropsychiatric symptoms associated with long COVID, which include anxiety, cognitive dysfunction, fatigue, and depression, may be linked to biological changes in the brain. Some research suggests these symptoms may be promoted by the premature aging of midbrain dopaminergic neurons, a process that may be reversible.

Because fluvoxamine is a low-cost medication that is already widely used and well-understood by clinicians, researchers believe it has significant potential for clinical application in managing PASC symptoms.

While the trial provides strong evidence for the management of established fatigue, the study also noted that metformin, while potentially helpful in preventing long COVID, did not alleviate fatigue once the condition had already developed.