The Real-World Effectiveness of Fluvoxamine Therapy in Mild to Moderate COVID-19 Patients; a Historical Cohort Study (Fluvoxa Trial)
M.D. M.Sc Taweegrit Siripongboonsitti, Kriangkrai Tawinprai, M.D.M.Sc Paruspak Payoong, Nithi Mahanonda
Journal of Infection and Public Health, doi:10.1016/j.jiph.2023.10.010
Background: Fluvoxamine (FVX) has been proposed as a potential treatment for severe COVID-19 by the σ-1 receptor agonist, which can reduce cytokine production. However, the efficacy of FVX remains controversial.
Methods: A historical retrospective cohort study was conducted in mild to moderate COVID-19 patients, 2:1 ratio of standard of care (SOC) and FVX treatments to assess the effectiveness of FVX in preventing deterioration by the fifth day of treatment. Results: Of 752 eligible patients, 234 received FVX while 518 received SOC, and there was no significant difference in the effectiveness of FVX and SOC in preventing clinical deterioration. On the fifth day after treatment, 86.1% of patients in the FVX-treated group did not experience clinical deterioration compared to 78.7% in the SOC group. Notably, the FVX group had higher rates of pneumonia development and hospitalization, requiring more oxygen supplementation while showing less reduction in viral shedding than the SOC group. However, no difference in mechanical ventilation use, ICU admission, and survival was observed.
Conclusion: Fluvoxamine treatment is failed to demonstrate effectiveness in preventing deterioration in mild to moderate COVID-19 and may lead to a higher incidence of pneumonia, hospitalization, and oxygen supplementation, necessitating careful consideration before prescribing the drug for COVID-19. Trial registration: Thai clinical trials registry (TCTR) no.
Consent for publication
Not applicable
Competing interests The authors declare that they have no competing interests.
Authors' Contributions T.S. had full access to all of the data in this study and took responsibility for the data's integrity and accuracy. T.S.-first authors. T.S.-Corresponding author, T.S., K.T., P.P., N.M. contributed equally to the study. Concept and design-T.S., N.M. Investigation-T.S., K.T., P.P., N.M., Acquisition, analysis, or interpretation of data: T.S.; Critical revision of the manuscript for important intellectual content: T.S.; Statistical analysis: A.K.; Obtained funding. N.M., T.S.; Administrative, technical, or material support: T.S.; Supervision: T.S., N.M.
Conflict of interest statement The authors have no interest to declare J o u r n a l P r e -p r o o f
References
Bernal, Da Silva, Musungaie, Kovalchuk, Gonzalez et al., Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med,
doi:10.1056/NEJMoa2116044Calusic, Marcec, Luksa, Jurkovic, Kovac et al., Safety and efficacy of fluvoxamine in COVID-19 ICU patients: An open label, prospective cohort trial with matched controls, Br J Clin Pharmacol,
doi:10.1111/bcp.15126Chuah, Chow, Hor, Cheng, Ker et al., Efficacy of Early Treatment With Favipiravir on Disease Progression Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19): A Randomized, Open-Label Clinical Trial, Clin Infect Dis,
doi:10.1093/cid/ciab962Fung, Liu, The ER stress sensor IRE1 and MAP kinase ERK modulate autophagy induction in cells infected with coronavirus infectious bronchitis virus, Virology,
doi:10.1016/j.virol.2019.05.002Guo, Harari, Chernecki, Thorlund, Forrest, Fluvoxamine for the Early Treatment of COVID-19: A Meta-analysis of Randomized Clinical Trials, Am J Trop Med Hyg,
doi:10.4269/ajtmh.21-1310Hammond, Leister-Tebbe, Gardner, Abreu, Wisemandle, Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2118542Hassanipour, Arab-Zozani, Amani, Heidarzad, Fathalipour et al., The efficacy and safety of Favipiravir in treatment of COVID-19: A systematic review and meta-analysis of clinical trials, Scientific reports,
doi:10.1038/s41598-021-90551-6Hoertel, Sánchez-Rico, De La Muela, Abellán, Blanco et al., Risk of Death in Individuals Hospitalized for COVID-19 With and Without Psychiatric Disorders: An Observational Multicenter Study in France, Biol Psychiatry Glob Open Sci,
doi:10.1016/j.bpsgos.2021.12.007Hoertel, Sánchez-Rico, Vernet, Beeker, Jannot et al., Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study, Mol Psychiatry,
doi:10.1038/s41380-021-01021-4Horita, Fukumoto, Global case fatality rate from COVID-19 has decreased by 96.8% during 2.5 years of the pandemic, J Med Virol,
doi:10.1002/jmv.28231Lee, Vigod, Bortolussi-Courval, Hanula, Boulware et al., Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-analysis, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2022.6269Lenze, Mattar, Zorumski, Stevens, Schweiger et al., Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial, Jama,
doi:10.1001/jama.2020.22760Mccarthy, Naggie, Boulware, Lindsell, Stewart et al., Fluvoxamine for Outpatient Treatment of COVID-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial, medRxiv,
doi:10.1101/2022.10.17.22281178.JournalPre-Németh, Szûcs, Vitrai, Juhász, Németh et al., Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study, Ideggyogy Sz,
doi:10.18071/isz.74.0389Reis, Santos Moreira-Silva, Silva, Thabane, Milagres et al., Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial, Lancet Glob Health,
doi:10.1016/s2214-109x(21)00448-4Schlienger, Meier, Effect of selective serotonin reuptake inhibitors on platelet activation: can they prevent acute myocardial infarction?, Am J Cardiovasc Drugs,
doi:10.2165/00129784-200303030-00001Seftel, Boulware, Prospective Cohort of Fluvoxamine for Early Treatment of Coronavirus Disease 19, Open Forum Infect Dis,
doi:10.1093/ofid/ofab050Seo, Kim, Bae, Park, Chung et al., Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center: A Preliminary Result of Randomized Controlled Trial, Infect Chemother,
doi:10.3947/ic.2021.0142Shrestha, Budhathoki, Khadka, Shah, Pokharel et al., Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and metaanalysis, Virology journal,
doi:10.1186/s12985-020-01412-zSiripongboonsitti, Ungtrakul, Tawinprai, Nimmol, Buttakosa et al., Efficacy of combination therapy of fluvoxamine and favipiravir vs favipiravir monotherapy to prevent severe COVID-19 among mild to moderate COVID-19 patients: Open-label randomized controlled trial (EFFaCo study), Int J Infect Dis,
doi:10.1016/j.ijid.2023.06.018Sukhatme, Reiersen, Vayttaden, Sukhatme, Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19, Front Pharmacol,
doi:10.3389/fphar.2021.652688Sánchez, Martínez-Sellés, García, Moreno Guillén, Rodríguez-Artalejo et al., Insights for COVID-19 in 2023, Rev Esp Quimioter,
doi:10.37201/req/122.2022Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention, Jama,
doi:10.1001/jama.2020.2648Zhou, Hill, Sarkar, Tse, Woodburn et al., β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, J Infect Dis,
doi:10.1093/infdis/jiab247Zhu, Zhang, Li, Yang, Song, A novel coronavirus from patients with pneumonia in China, New England Journal of Medicine,
doi:10.1056/nejmoa2001017
