Fluvoxamine Not Efficacious Against Clinical Deterioration in Unvaccinated COVID-19

Peak disease severity and rates of clinical deterioration did not significantly differ between outpatients with COVID-19 infection who received fluvoxamine vs placebo.

Fluvoxamine is not effective in preventing clinical deterioration in unvaccinated outpatients infected with COVID-19, according to study results published in Open Forum Infectious Diseases

Researchers conducted a randomized, double-blinded, placebo-controlled, fully-remote, multicenter trial from December 2020 to May 2021 across the United States and Canada to evaluate the efficacy of fluvoxamine in preventing clinical deterioration in unvaccinated outpatients with acute COVID-19 infection.

Study patients were aged 30 years and older with self-confirmed symptomatic COVID-19 infection and at least 1 risk factor for progression to severe disease. Patients were stratified by sex, study site, and age group (<40 vs ≥40 years) and randomly assigned 1:1 to receive either fluvoxamine or placebo for 15 days. The primary modified intention-to-treat (mITT) population comprised patients with baseline oxygen saturation of at least 92% who had initiated treatment within 7 days of symptom onset.

The primary outcome was clinical deterioration within 15 days, defined as dyspnea and/or hospitalization for dyspnea or pneumonia, as well as reduced oxygenation saturation (<92% on room air) with or without the need for supplemental oxygen. The researchers also measured peak disease severity via the World Health Organization (WHO) Therapeutic Trial Synopsis 9-point scale. Between-group differences in peak disease severity scores were evaluated via Fisher exact testing.

Further studies are warranted to examine the efficacy of fluvoxamine for COVID-19, alone and in combination with other therapies…

A total of 547 patients met mITT criteria, of whom 272 received fluvoxamine and 275 received placebo. Overall, the median age was 47 (IQR, 41-55) years, 62% were women, 27% self-identified as non-White, and the median symptom duration at treatment initiation was 5 (IQR, 4-6) days. 

Clinical deterioration was observed in 13 (4.8%) fluvoxamine recipients and 15 (5.5%) placebo recipients (absolute difference at day 15, 0.68%; 95% CI, -3.0% to 4.4%; log-rank P =.91). Mean scores on the WHO peak disease severity scale were not significantly different between the groups; however, placebo recipients were more likely to require hospitalization with supplemental oxygen.

Further analysis showed that 60.3% and 74.5% of patients in the fluvoxamine and placebo groups, respectively, received at least 80% of expected medication doses (per-protocol analysis criteria). Between-group clinical deterioration rates did not significantly differ in the per-protocol population (4.9% vs 5.4%, respectively).

Severe adverse events, the majority of were COVID-19-related hospitalization, were observed in 11 (4.0%) patients in the fluvoxamine group and 12 (4.4%) in the placebo group. Of note, no severe adverse events were attributed to fluvoxamine, and there were no mortality events among the mITT population.

Limitations of this study include the fully-remote study design, which did not allow for verification of COVID-19 infection, as well as lower rates of clinical deterioration than anticipated. 

The researchers concluded, “further studies are warranted to examine the efficacy of fluvoxamine for COVID-19, alone and in combination with other therapies, particularly in regions with higher rates of clinical deterioration and hospitalization due to COVID-19, lower rates of vaccination, or where access to highly effective COVID-19 treatments remains low.”

This article originally appeared on Infectious Disease Advisor


Reiersen AM, Mattar C, Ignacio RAB, et al. The STOP COVID 2 study: fluvoxamine vs placebo for outpatients with symptomatic COVID-19, a fully-remote randomized controlled trial.  Open Forum Infect Dis. Published online, August 8, 2023. doi:10.1093/ofid/ofad419.