Fluvoxamine for the Early Treatment of COVID-19: A Meta-analysis of Randomized Clinical Trials

Abstract

Fluvoxamine is widely prescribed as an antidepressant. Recent studies show the drug may have a clinical benefit in treating COVID-19. We aimed to perform a meta-analysis of the existing randomized trials of fluvoxamine compared with placebo on the early treatment of COVID-19 patients. We included only randomized clinical trials enrolling ambulatory patients with early-stage disease (symptoms > 7 days) for the prevention of hospitalization. We searched MEDLINE, and clinicaltrials.gov databases to identify trials and extract data with clarifications from the study investigators. We performed a fixed-effects meta-analysis and sensitivity analyses via R to evaluate the pooled estimate of hospitalization. We included three randomized trials: STOP COVID 1 and 2, and the TOGETHER Trial. The studies included a total of 2,196 patients. The STOP COVID trials measured clinical deterioration whereas the TOGETHER Trial measured hospitalization as the primary outcome. All trials reported on hospitalization up to day 28. The meta-analysis results show that patients receiving fluvoxamine were 31% less likely to experience clinical deterioration or hospitalization compared with placebo (risk ratio, 0.69; 95% CI, 0.54–0.88). A sensitivity analysis using the definition of hospitalization resulted in a risk reduction of 21% (95% CI, 0.60–1.03). Data from three randomized controlled trials show that fluvoxamine was associated with a reduction in the primary outcome measure (either clinical deterioration or composite outcome of hospitalization or extended emergency setting observation), although analysis of hospitalization-only was not statistically significant. More evidence from future trials is still needed to support the findings of this meta-analysis.

Antidepressant Drugs and COVID-19: A Review of Basic and Clinical Evidence

“…As a result of the high level of interest in the clinical trials conducted on fluvoxamine, two meta-analysis have recently been published [ 98 , 99 ]. The studies included in both cases were the STOP COVID 1 and 2 and the TOGETHER studies.…”

Correspondence on Fluvoxamine Treatment of Patients with Symptomatic COVID-19

“…The severity of symptomatic COVID-19, concurrent underlying medical conditions, and additional alternative therapies to fluvoxamine might affect the outcome and should be analyzed. In a recent meta-analysis, Guo et al mentioned the need for the analysis of the possible confounding factors determining the effect of fluvoxamine in clinical settings [ 3 ]. However, Guo et al showed a trend of there being a possible role of fluvoxamine in reducing severe clinical infection [ 3 ].…”

“…In a recent meta-analysis, Guo et al mentioned the need for the analysis of the possible confounding factors determining the effect of fluvoxamine in clinical settings [ 3 ]. However, Guo et al showed a trend of there being a possible role of fluvoxamine in reducing severe clinical infection [ 3 ].…”

Reply: Correspondence on Fluvoxamine Treatment of Patients with Symptomatic COVID-19

“…The correspondence article in this journal presents a recent meta-analysis of randomized clinical trials on fluvoxamine for the early treatment of coronavirus disease 2019 (COVID-19) [ 2 ], which included three randomized trials: STOP COVID 1 [ 3 ] and 2, and TOGETHER trial [ 4 ]. This meta-analysis results showed that patients receiving fluvoxamine compared with placebo had a 31.0% risk reduction in clinical deterioration or hospitalization (risk ratio [RR]: 0.69; 95% confidence interval [CI]: 0.54 – 0.88).…”

“…One of three trials included in the meta-analysis was STOP COVID 2, which was a follow-up study of STOP COVID 1 and included 547 patients [ 2 ]. Although this trial was stopped due to operational futility with increasing vaccination rates and an overall decrease in the events, they could not demonstrate statistically significant difference in clinical deterioration between patients with fluvoxamine and placebo (RR: 0.88; 95% CI: 0.42 – 1.81).…”