Early Treatment with Fluvoxamine Reduces COVID-19 Hospitalizations

Vaccine allocation and availability is limited in some areas, so some investigators are looking to existing medicines to treat COVID-19. Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) and a σ-1 receptor (S1R), may offer anti-inflammatory and antiviral effects.

A placebo-controlled, randomized, adaptive platform study study published in The Lancet this week sought to assess the efficacy of fluvoxamine for preventing hospitalization in adults with COVID-19. Investigators in Minas Gerais, Brazil recruited participants 18 years or older who presented to an outpatient care setting with a clinical condition indicative of COVID-19 and symptoms beginning within 7 days of the screening date, or a positive COVID-19 diagnostic test within 7 days of symptom onset. Participants also had at least one comorbidity designating them as high-risk for severe COVID-19 disease requiring hospitalization.

All participants received standard care for COVID-19 at public health facilities. They were randomly assigned and immediately administered 100 mg of fluvoxamine twice a day for 10 days or a corresponding placebo. Investigators collected outcome data on days 1-5, 7, 10, 14, and 28 in person or via the telephone or video-teleconferencing.

By August 5, 2021, 1497 participants were randomly assigned fluvoxamine (n=741) or placebo (n=756). The median age was 50 years (ranging from 18-102), and 862 (58%) were women. Most participants, 1428 (95%), identified as mixed race, 12 (1%) as white, 10 (1%) as Black or African, and the remaining 47 (3%) self-identified as unknown.

In the fluvoxamine group, 79 (11%) participants had a primary outcome event, as compared to 119 (16%) in the placebo group. Most events (87%) were hospitalizations. Investigators found a statistically significant absolute risk reduction of 5.0% and 32% RR reduction in the fluvoxamine group. The Bayesian beta-binomial model revealed evidence that fluvoxamine reduced the composite primary endpoint of hospitalization (defined as retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19). The probability that the event rate was lower in the fluvoxamine group than the intention-to-treat population was 99%. There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis (odds ratio [OR] 0.68, 95% CI: 0.36–1.27), and 1 death in the fluvoxamine group and 12 in the placebo group for the per-protocol population (OR 0.09; 95% CI 0.01–0.47).

According to the study authors, “This study is only the second study to show an important treatment benefit for a repurposed drug in the early treatment population...Given fluvoxamine's safety, tolerability, ease of use, low cost, and widespread availability, these findings might influence national and international guidelines on the clinical management of COVID-19.”