Clinical Efficacy and Safety of Fluvoxamine in COVID-19 Patients: An Umbrella Review of Systematic Reviews and Meta-Analyses

Introduction: Fluvoxamine is an agonist for the sigma-1 receptor, through which it controls inflammation. It helps reduce the cytokine storm associated with the COVID-19 virus by regulating the production of IL-6 and gene expression. This review of systematic reviews (SRs) aims to summarize the effects of fluvoxamine in treatment of COVID-19. Methods: This umbrella review (CRD42025592203) of SRs and meta-analyses investigated the safety and efficacy of fluvoxamine for treatment in COVID-19 patients, irrespective of disease severity and age. Comprehensive searches were conducted from inception to December 12, 2024, covering PubMed, Cochrane CENTRAL, Google Scholar, and Cochrane COVID-19 resources. A qualitative synthesis of evidence was performed. The AMSTAR2 tool was used to assess the methodological quality of the included SRs. Results: Eleven reviews published in 12 publications that reported the use of fluvoxamine in COVID-19 patients were finally included as part of the synthesis. The studies reported a lower mortality rate with fluvoxamine than with placebo, but only four studies reported statistical significance. Five reported a statistically significant reduction in hospitalization risk for patients treated with fluvoxamine compared to controls. Only one review evaluated COVID-19 progression, reporting a non-significant decrease in the risk of disease progression with fluvoxamine compared to placebo. Higher dosages of fluvoxamine compared to lower doses yielded better outcomes. Conclusion: Although fluvoxamine may have potential benefits in reducing COVID-19-associated mortality and hospitalization, our findings do not support a significant role in preventing disease progression or clinical deterioration. Further research is needed to compare the efficacies of different dosages.