Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events. -JAMA
Overall, 65 persons opted to receive fluvoxamine 50mg twice daily and 48 declined. Incidence of hospitalization was 0% (0/65) with fluvoxamine and 12.5% (6/48) with observation alone. At 14 days, residual symptoms persisted in 0% (0/65) with fluvoxamine and 60% (29/48) with observation.
Possible mechanisms common with other antidepressants
The Enzyme Hypothesis- Fluvoxamine inhibits acid Sphingomyelinase which is needed for viruses to enter the cell -Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine. Emerging Microbes and infections vol 9, 2020. https://pubmed.ncbi.nlm.nih.gov/32975484/
Ceramide-door theory- Ceramides, which act as doors to let the virus enter the cells are also inhibited because of inhibition of enzyme Acid Sphingomyelinase by Fluvoxamine. Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells. Cell Reports Medicine Nov 2020. https://pubmed.ncbi.nlm.nih.gov/33163980/
The Lysosome theory- Fluvoxamine has lysosomotropic properties which inhibit movement and dissemination of virus particles in the lysosome pathway in the cells of the body. Widely available lysosome targeting agents should be considered as potential therapy for COVID-19. International Journal of Antimicrobial Agents. Aug 2020.(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275137/
Increasing Melatonin levels in the brain. Fluvoxamine increases nighttime levels of melatonin 2-3 times through its inhibition of the melatonin-metabolizing liver enzymes CYP1A2 and CYP2C19.Fluvoxamine, Melatonin and COVID-19. Psychopharmacology, Jan 2021 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779245/
Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events. -JAMA
Overall, 65 persons opted to receive fluvoxamine 50mg twice daily and 48 declined. Incidence of hospitalization was 0% (0/65) with fluvoxamine and 12.5% (6/48) with observation alone. At 14 days, residual symptoms persisted in 0% (0/65) with fluvoxamine and 60% (29/48) with observation.
Possible mechanisms common with other antidepressants
The Enzyme Hypothesis- Fluvoxamine inhibits acid Sphingomyelinase which is needed for viruses to enter the cell -Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine. Emerging Microbes and infections vol 9, 2020. https://pubmed.ncbi.nlm.nih.gov/32975484/
Ceramide-door theory- Ceramides, which act as doors to let the virus enter the cells are also inhibited because of inhibition of enzyme Acid Sphingomyelinase by Fluvoxamine. Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells. Cell Reports Medicine Nov 2020. https://pubmed.ncbi.nlm.nih.gov/33163980/
The Lysosome theory- Fluvoxamine has lysosomotropic properties which inhibit movement and dissemination of virus particles in the lysosome pathway in the cells of the body. Widely available lysosome targeting agents should be considered as potential therapy for COVID-19. International Journal of Antimicrobial Agents. Aug 2020.(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275137/
Increasing Melatonin levels in the brain. Fluvoxamine increases nighttime levels of melatonin 2-3 times through its inhibition of the melatonin-metabolizing liver enzymes CYP1A2 and CYP2C19.Fluvoxamine, Melatonin and COVID-19. Psychopharmacology, Jan 2021 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779245/