Antidepressant Fluvoxamine May Reduce Fatigue in Long COVID: Study

A new study published in the recent issue of Annals of Internal Medicine journal found that antidepressant fluvoxamine reduced fatigue in individuals with long COVID when compared to placebo, though the benefit appears to be limited to the short term.

The study focused on post-acute sequelae of SARS-CoV-2 (long COVID) which continues to challenge clinicians worldwide due to its complex and varied symptoms. Fatigue remains one of the most prevalent complaints, often lasting months after the initial infection and severely affecting daily functioning.

This randomized, placebo-controlled adaptive trial enrolled 399 adults in Brazil who had experienced fatigue for at least 90 days following confirmed COVID-19 infection. Participants were divided into three groups, where one group received fluvoxamine (100 mg twice daily), another received Metformin (750 mg twice daily), and a third received a placebo. The treatment period lasted 60 days, with follow-up extending to 90 days.

The primary measure of success was improvement in fatigue levels, which was assessed using the Fatigue Severity Scale (FSS). The results showed that patients treated with fluvoxamine experienced a statistically significant reduction in fatigue when compared with those given a placebo. By day 60, the average improvement was modest but meaningful, and the benefit appeared to increase by day 90, which suggests a sustained effect even after treatment ended.

In addition to reducing fatigue, fluvoxamine was associated with improved quality-of-life scores, with a high probability that these benefits were not due to chance. This research observed that patients reported better overall well-being and daily functioning. Also, metformin did not demonstrate a significant impact on fatigue symptoms in this study.

Adverse events occurred less frequently in the fluvoxamine group (20%) when compared to both the metformin (28.8%) and placebo (29.7%) groups. Severe adverse events were rare across all participants, indicating that the treatments were generally well tolerated. 

This trial focused only on fatigue, leaving unanswered questions about its effects on other common long COVID symptoms such as cognitive impairment or shortness of breath. Overall, fluvoxamine was found to be effective in reducing fatigue and improving the quality of life in patients facing long COVID.

Source:

Reis, G., Dos Santos Moreira Silva, E. A., Medeiros Silva, D. C., Thabane, L., Ferreira, T. S., Reis, L. L. F., Figueiredo Guimaraes Almeida, A. P., Menezes Amaral, M., Savassi, L. C. M., de Souza Campos, V. H., Campos Simplicio, M. I., Barra Ribeiro, L., de Souza Medeiros, T., Campos Siqueira, T., Vieira, T. S., Drumond Rausse, N., Garofolo, T. C., Fagundes Silva, E. C., Harari, O., … REVIVE Investigators. (2026). The effect of fluvoxamine and metformin for fatigue in patients with long COVID : An adaptive randomized trial. Annals of Internal Medicine, ANNALS-25-03959. https://doi.org/10.7326/ANNALS-25-03959