Fluvoxamine for Outpatient COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-Analysis

Abstract

Importance: Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly therapies that prevent hospitalization. Objective: 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: Completed outpatient trials with available results which compared fluvoxamine to placebo. Data Extraction and Synthesis: We followed the PRISMA 2020 guidelines. We extracted study details in terms of inclusion criteria, trial demographics and the pre-specified outcome of all-cause hospitalization. Risk of bias was assessed by the Cochrane Risk of Bias 2 tool. We conducted a frequentist random effects meta-analysis, as well as two sensitivity analyses using a Bayesian random effects meta-analysis with different estimates of prior probability: a weakly neutral prior (50% chance of efficacy with 95% confidence interval for Risk Ratio [RR] between 0.5 and 2) and a moderately optimistic prior (85% chance of efficacy). We contextualized the results by estimating the probability of any effect (RR ≤1) and moderate effect (RR ≤0.9) on reducing hospitalization. Main Outcome(s) and Measure(s): All cause hospitalization. Results: 2196 participants were included from 3 identified trials. The risk ratios for hospitalization were 0.75 (95%CI, 0.57-0.97) for the frequentist analysis, 0.78 (95%CI 0.58-1.08) for the Bayesian weakly neutral prior, and 0.73 (95%CI, 0.53-1.01) for the Bayesian moderately optimistic prior. Depending on the scenario, the probability of any effect on hospitalization ranged from 94.1% to 98.3% and a moderate effect from 81.6% to 91.1%. Conclusions and Relevance: Under a variety of assumptions, fluvoxamine shows a high probability of preventing hospitalization in outpatients with COVID-19. While ongoing randomized trials are important to evaluate alternative doses, explore the effectiveness in vaccinated patients, and provide further refinement to these estimates, fluvoxamine could be recommended as a treatment option, particularly in resource-limited settings or persons without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals.

Difficulty in Repurposing Selective Serotonin Reuptake Inhibitors and Other Antidepressants with Functional Inhibition of Acid Sphingomyelinase in COVID-19 Infection

“…Furthermore, there are currently 2 meta-analysis in a preprint state (Kacimi et al, 2021(Kacimi et al, , submitted 2021Lee et al, 2021Lee et al, , submitted 2021) and it should be noted that they did not include the same studies, only 2 studies in common on the 3 included studies. A meta-analysis has concluded that fluvoxamine has not shown significant efficacy in reducing either the mortality rates or mechanical ventilation while promising results in decreasing the likelihood for hospitalization in patients with COVID-19 (Kacimi et al, 2021(Kacimi et al, , submitted 2021.…”

Fluvoxamine for symptomatic outpatients with COVID-19

“…Trials primarily enrolled unvaccinated adult outpatients at high risk for serious COVID-19 outcomes. 2 For pregnant patients, caution and obstetrical consultation are advised. Fluvoxamine is not recommended for pediatric patients.…”

“…3 Fluvoxamine was generally well tolerated in the clinical trials Treatment was either 100 mg twice daily for 10 days, or started at 50 mg once daily, titrated to 100 mg twice daily over 2-3 days, and up to 3 times daily as tolerated for a total of 10-15 days. 2 Treatment ended without taper. 2 Patient-reported adverse events were similar in the fluvoxamine and placebo groups, and included mild headache and gastrointestinal symptoms.…”

“…2 Treatment ended without taper. 2 Patient-reported adverse events were similar in the fluvoxamine and placebo groups, and included mild headache and gastrointestinal symptoms. 2…”

“…1 A meta-analysis of 2196 patients with COVID-19 from 3 randomized controlled trials concluded that fluvoxamine had a high probability of preventing hospital admission or observation in the emergency department for more than 24 hours, compared with placebo. 2 The Ontario Science Table states that fluvoxamine may be considered for mildly ill patients within 7 days of symptom onset. 3 This article has been peer reviewed.…”