Fluvoxamine Reduces Fatigue and Improves Quality of Life in Long COVID Patients: Study
A recent breakthrough randomized, placebo-controlled trial found that fluvoxamine significantly reduces debilitating long COVID fatigue with a remarkably low 20.0% adverse event rate, providing clinicians with a potent new tool against post-viral exhaustion. as detailed in the Annals of Internal Medicine in April 2026.
Long Coronavirus Disease (COVID), defined by symptoms persisting after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, presents a significant clinical hurdle due to biological drivers like mitochondrial dysfunction and endothelial impairment, yet effective treatments for its most debilitating feature—fatigue—have remained elusive. To address this gap, lead investigator G. Reis and colleagues in Brazil designed an adaptive trial to evaluate whether the anti-inflammatory properties of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), or metformin could provide the symptomatic relief that current supportive care fails to deliver.
Therefore, the randomized, placebo-controlled adaptive trial recruited 399 adults suffering from fatigue for at least 90 days post-infection and administered either 100 mg of fluvoxamine twice daily, 750 mg of metformin twice daily, or a placebo over a 60-day treatment window across 22 outpatient clinics. The research team excluded patients with major depressive disorder to isolate fatigue effects and utilized the Fatigue Severity Scale (FSS) as the primary endpoint alongside secondary quality of life measures, ensuring a robust analytical framework for comparing these potential interventions through a 90-day follow-up period.
Key Clinical Findings of the Study Include:
• Fluvoxamine Efficacy: The study demonstrated that fluvoxamine produced a statistically significant reduction in fatigue by day 60, with these improvements remaining durable through the 90-day follow-up.
• Metformin Futility: Conversely, the study observed no meaningful benefit regarding fatigue levels for the metformin group, leading to the early cessation of that arm following an interim analysis.
• Quality of Life: In the study, consistent enhancements in overall well-being and life quality were reported by participants in the fluvoxamine group at every assessment point, a trend not mirrored in the metformin or placebo cohorts.
• Tolerability Profile: Safety data from the study highlighted that adverse events occurred in only 20.0% of the fluvoxamine group, which was lower than the 28.8% seen with metformin and 29.7% with the placebo.
The results suggest that fluvoxamine is a superior candidate for treating long COVID fatigue, as evidenced by its 20.0% adverse event rate and its capacity to provide sustained symptomatic relief compared to both metformin and placebo. These findings are particularly compelling given that the fluvoxamine arm was stopped early for superiority, reinforcing the statistical strength of the observed improvements in patient quality of life.
Thus, the study concludes that clinicians may consider the use of fluvoxamine to help manage fatigue and bolster general well-being in patients suffering from prolonged symptoms after a SARS-CoV-2 infection.
Although these findings offer a promising path forward, the study's limitation to a 90-day window and a specific geographic population in Brazil highlights a need for future investigations that include biological markers to clarify the underlying mechanisms of recovery.
Reference
Reis G et al. The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID : An Adaptive Randomized Trial. Ann Intern Med. 2026.
