raj authored on July 16, 2022, 9:24 p.m. | | Additions are marked like this |
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been trialed for possible therapeutic use in COVID-19 and is showing promising results. 
COVID-19 clinical trialsTrials that have been completed and publishedSTOP COVID: Fluvoxamine showed promise in a double-blinded, randomized, placebo-controlled trial of 152 COVID-19-positive outpatients. In a paper published in November 2020 in the Journal of the American Medical Association: 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 In a prospective cohort study of fluvoxamine for an outbreak at the Golden Gate Fields racetrack: 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. TOGETHER TRIAL: Repurposed Approved Therapies for Outpatient Treatment of Patients With Early-Onset COVID-19 and Mild Symptoms - Parallel assignment, 4-arm randomized control trial that includes a Fluvoxamine arm. Brazilian study looked at the effect of early treatment with fluvoxamine on the risk of emergency care and hospitalization among patients with COVID-19. They used Bayesian analysis, which showed Bayesian credible interval [95% BCI]: 0·52-0·88), with a probability of Fluvoxamine superiority of 99·8% over placebo in reducing the need for hospitalization. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext Informational website on the TOGETHER trial. Feb 9, 2021 news article about this trial. COVID-OUT TRIAL: Outpatient Treatment for SARS-CoV-2 Infection, a Factorial Randomized Trial. STOP COVID-2 : Fluvoxamine for Early Treatment of Covid-19 (Stop Covid 2) - An expansion of the smaller contactless (telemedicine) randomized control trial above to 1100 participants. Early treatment, outpatient. Trials in progress
Clinical GuidelinesFluvoxamine in NIH CVOID-19 treatment guidelines. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/fluvoxamine/ Mechanism of possible benefit?A review of all the mechanisms of action of Fluvoxamine and its role in COVID-19 https://www.frontiersin.org/articles/10.3389/fphar.2021.652688/full Sigma-1 receptorMechanisms of potential benefit in COVID-19 may include sigma-1 receptor agonism. See "Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor" and "Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis".
Possible mechanisms common with other antidepressantsThe 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 can 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779245/ Modulating endocytic trafficking of SARS-CoV-2 spike protein. https://www.biorxiv.org/content/10.1101/2021.06.15.448391v1 As an antidepressantAn observational study of 7,345 hospitalized COVID-19 patients hinted at possible benefit of prior antidepressant usage. As an anti-viralIn an October, 2020 preprint, fluoxetine, a related SSRI, showed in vitro anti-SARS-CoV-2 activity in Vero and Calu-3 cells. Other methods of possible benefitNews coverage
Notes on side effects & interactionsFluvoxamine does not play well with caffeine — it makes a cup of coffee last 31-35 hours instead of 5 (see also and also). For more information on potential interactions see:
See also
| Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been trialed for possible therapeutic use in COVID-19 and is showing promising results.
COVID-19 clinical trialsTrials that have been completed and publishedSTOP COVID: Fluvoxamine showed promise in a double-blinded, randomized, placebo-controlled trial of 152 COVID-19-positive outpatients. In a paper published in November 2020 in the Journal of the American Medical Association: 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 In a prospective cohort study of fluvoxamine for an outbreak at the Golden Gate Fields racetrack: 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. TOGETHER TRIAL: Repurposed Approved Therapies for Outpatient Treatment of Patients With Early-Onset COVID-19 and Mild Symptoms - Parallel assignment, 4-arm randomized control trial that includes a Fluvoxamine arm. Brazilian study looked at the effect of early treatment with fluvoxamine on the risk of emergency care and hospitalization among patients with COVID-19. They used Bayesian analysis, which showed Bayesian credible interval [95% BCI]: 0·52-0·88), with a probability of Fluvoxamine superiority of 99·8% over placebo in reducing the need for hospitalization. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext Informational website on the TOGETHER trial. Feb 9, 2021 news article about this trial. COVID-OUT TRIAL: Outpatient Treatment for SARS-CoV-2 Infection, a Factorial Randomized Trial. STOP COVID-2 : Fluvoxamine for Early Treatment of Covid-19 (Stop Covid 2) - An expansion of the smaller contactless (telemedicine) randomized control trial above to 1100 participants. Early treatment, outpatient. Trials in progress
Clinical GuidelinesFluvoxamine in NIH CVOID-19 treatment guidelines. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/fluvoxamine/ Mechanism of possible benefit?A review of all the mechanisms of action of Fluvoxamine and its role in COVID-19 https://www.frontiersin.org/articles/10.3389/fphar.2021.652688/full Sigma-1 receptorMechanisms of potential benefit in COVID-19 may include sigma-1 receptor agonism. See "Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor" and "Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis".
Possible mechanisms common with other antidepressantsThe 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 can 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779245/ Modulating endocytic trafficking of SARS-CoV-2 spike protein. https://www.biorxiv.org/content/10.1101/2021.06.15.448391v1 As an antidepressantAn observational study of 7,345 hospitalized COVID-19 patients hinted at possible benefit of prior antidepressant usage. As an anti-viralIn an October, 2020 preprint, fluoxetine, a related SSRI, showed in vitro anti-SARS-CoV-2 activity in Vero and Calu-3 cells. Other methods of possible benefitNews coverage
Notes on side effects & interactionsFluvoxamine does not play well with caffeine — it makes a cup of coffee last 31-35 hours instead of 5 (see also and also). For more information on potential interactions see:
See also
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