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Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-analysis

Lee et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2022.6269 (date from preprint)
Dec 2021  
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26th treatment shown to reduce risk in November 2021
*, now known with p = 0.00014 from 21 studies, recognized in 3 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Systematic review and meta analysis of outpatient RCTs, showing hospitalization RR 0.75 [0.57-0.97]. For discussion see
6 meta analyses show significant improvements with fluvoxamine for mortality Deng, hospitalization Deng, Deng (B), Lee, Lu, Marcec, and severity Nakhaee.
Currently there are 21 fluvoxamine for COVID-19 studies, showing 43% lower mortality [12‑62%], 42% lower ventilation [-151‑86%], 10% higher ICU admission [-72‑326%], 51% lower hospitalization [8‑73%], and 27% fewer cases [18‑35%].
Lee et al., 21 Dec 2021, peer-reviewed, 8 authors.
This PaperFluvoxamineAll
Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization
MD, MPH Todd C Lee, MD, MSc Simone Vigod, Émilie Bortolussi-Courval, BSc Ryan Hanula, MD, MPH David R Boulware, MD Eric J Lenze, MD, MPE Angela M Reiersen, MD, MSc Emily G Mcdonald
JAMA Network Open, doi:10.1001/jamanetworkopen.2022.6269
IMPORTANCE Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly for therapies that prevent hospitalization. OBJECTIVE To perform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19. DATA SOURCES World Health Organization International Clinical Trials Registry Platform and STUDY SELECTION Studies with completed outpatient trials with available results that compared fluvoxamine with placebo were included. DATA EXTRACTION AND SYNTHESIS The PRISMA 2020 guidelines were followed and study details in terms of inclusion criteria, trial demographics, and the prespecified outcome of all-cause hospitalization were extracted. Risk of bias was assessed by the Cochrane Risk of Bias 2 tool and a bayesian random effects meta-analysis with different estimates of prior probability was conducted: a weakly neutral prior (50% chance of efficacy with 95% CI for risk ratio [RR] between 0.5 and 2.0) and a moderately optimistic prior (85% chance of efficacy). A frequentist random-effects metaanalysis was conducted as a senstivity analysis, and the results were contextualized by estimating the probability of any association (RR Յ 1) and moderate association (RR Յ 0.9) with reduced hospitalization. MAIN OUTCOMES AND MEASURES All-cause hospitalization. RESULTS This systematic review and meta-analysis of 3 randomized clinical trials and included 2196 participants. The RRs for hospitalization were 0.78 (95% CI, 0.58-1.08) for the bayesian weakly neutral prior, 0.73 (95% CI, 0.53-1.01) for the bayesian moderately optimistic prior, and 0.75 (95% CI, 0.58-0.97) for the frequentist analysis. Depending on the scenario, the probability of any association with reduced hospitalization ranged from 94.1% to 98.6%, and the probability of moderate association ranged from 81.6% to 91.8%. CONCLUSIONS AND RELEVANCE In this systematic review and meta-analysis of data from 3 trials, under a variety of assumptions, fluvoxamine showed a high probability of being associated with reduced hospitalization in outpatients with COVID-19. Ongoing randomized trials are important to evaluate alternative doses, explore the effectiveness in vaccinated patients, and provide further refinement to these estimates. Meanwhile, fluvoxamine could be recommended as a management (continued) Key Points Question Is early administration of fluvoxamine associated with hospitalization in symptomatic adult outpatients with confirmed COVID-19? Findings In this systematic review and bayesian meta-analysis of 3 clinical trials, which accounted for varying prior probabilities coupled with a frequentist sensitivity analysis, there was a high probability (94.1%-98.6%) that fluvoxamine was associated with a reduced risk for hospitalization, with a frequentist risk ratio of 0.75 (95% CI, 0.58-0.97). Meaning These findings suggest that fluvoxamine, a widely available and..
Author Contributions: Dr Lee had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Additional Information: This study was not registered and a full review protocol was not written because it was initially conducted as a rapid review and then changed to a full systematic review and meta-analysis.
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