Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19

Vikas P Sukhatme, Angela M Reiersen, Sharat J Vayttaden, Vidula V Sukhatme, Vikas P Sukhatme, Angela M Reiersen, Sharat J Vayttaden, Vidula V Sukhatme

Abstract

Fluvoxamine is a well-tolerated, widely available, inexpensive selective serotonin reuptake inhibitor that has been shown in a small, double-blind, placebo-controlled, randomized study to prevent clinical deterioration of patients with mild coronavirus disease 2019 (COVID-19). Fluvoxamine is also an agonist for the sigma-1 receptor, through which it controls inflammation. We review here a body of literature that shows important mechanisms of action of fluvoxamine and other SSRIs that could play a role in COVID-19 treatment. These effects include: reduction in platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, regulation of inositol-requiring enzyme 1α-driven inflammation and increased melatonin levels, which collectively have a direct antiviral effect, regulate coagulopathy or mitigate cytokine storm, which are known hallmarks of severe COVID-19.

Keywords: SARS-CoV-2; acute respiratory distress syndrome; cytokine storm; inflammation; interleukins.

Conflict of interest statement

Author VVS was employed by the company GlobalCures, Inc. Author AR has received research support for clinical trials of fluvoxamine for COVID-19 from the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University, Fast Grants, and the COVID-19 Early Treatment Fund, and she is an inventor on a patent application filed by Washington University in St. Louis, which is relevant to methods of treating COVID-19, including fluvoxamine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Sukhatme, Reiersen, Vayttaden and Sukhatme.

Figures

FIGURE 1
FIGURE 1
Potential anti-COVID-19 mechanisms of action of fluvoxamine. Figure created using Biorender.

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