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- Title
Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-analysis.
- Authors
Lee, Todd C.; Vigod, Simone; Bortolussi-Courval, Émilie; Hanula, Ryan; Boulware, David R.; Lenze, Eric J.; Reiersen, Angela M.; McDonald, Emily G.
- Abstract
This systematic review and meta-analysis examines randomized clinical trial evidence for fluvoxamine to prevent hospitalization of patients with COVID-19. 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 inexpensive treatment for outpatients with COVID-19, was associated with a reduction in hospitalizations. 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 ClinicalTrials.gov. 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 meta-analysis was conducted as a senstivity analysis, and the results were contextualized by estimating the probability of any association (RR ≤ 1) and moderate association (RR ≤ 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 option, particularly in resource-limited settings or for individuals without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals.
- Subjects
EVALUATION of medical care; COVID-19; META-analysis; FLUVOXAMINE; SYSTEMATIC reviews; HOSPITAL care; DESCRIPTIVE statistics; SENSITIVITY &; specificity (Statistics); OUTPATIENT services in hospitals; PROBABILITY theory; EVALUATION
- Publication
JAMA Network Open, 2022, Vol 5, Issue 4, pe226269
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2022.6269