A randomized clinical trial found that the antidepressant fluvoxamine significantly reduces long COVID–related fatigue, one of the condition’s most persistent and debilitating symptoms, while the diabetes drug metformin showed no benefit. Patients taking fluvoxamine reported steadily improving fatigue and quality-of-life scores over 60 to 90 days, with fewer side effects than those on placebo. The findings are published in Annals of Internal Medicine.
Researchers from the Brazilian Biomedical Research Institute and colleagues assessed the efficacy of fluvoxamine and metformin for long COVID fatigue among 399 people at 22 outpatient sites in Brazil between October 2023 and February 2025. Eligible participants had been experiencing fatigue for at least 90 days after infection and were assigned to fluvoxamine, metformin, or a placebo for 60 days. Researchers measured changes using a standard fatigue severity scale. Fluvoxamine produced a meaningful reduction in fatigue by day 60, with continued improvement at day 90, and also boosted overall quality-of-life scores. Metformin did not show any significant effect. While all treatments were generally safe, fluvoxamine had fewer reported adverse events. The authors conclude that fluvoxamine may offer a viable treatment option for long COVID fatigue, though longer-term effects remain unknown. However, an important limitation of the study was the absence of assessment for a history of depression. Thus, whether the treatment effect was due to a direct effect on long COVID or to an effect on baseline depression is uncertain.
