In the Search for COVID-19 Therapies, Fluvoxamine Lacks Significant Impact

Matthew McCarthy, MD

In an investigation comparing low-dose fluvoxamine treatment with placebo, results showed no meaningful difference of symptom duration in adults with COVID-19. Participating patients who received the intervention were given 50 mg of fluvoxamine twice daily for 10 days; according to investigators, this dose and treatment duration was not supported by these data.

While novel oral antiviral therapies for COVID-19 have shown success in some patient populations, like unvaccinated individuals, there’s more to be determined in regard to how effective the recommended therapies are for vaccinated patients with mild-to-moderate COVID-19.

“Repurposing approved drugs developed for other conditions presents an attractive strategy to identify new treatment options and expand access to potentially lifesaving care,” Matthew McCarthy, MD, Weill Cornell Medicine, and a team of investigators wrote.

Repurposing Medications as Potential Therapies for COVID-19

The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial is an ongoing evaluation that was created to examine the effect of repurposed medications on outpatients with mild-to-moderate COVID-19. The study population consisted of adults aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less

Enrollment took place from August 2021-May 2022, at 91 sites in the US. Upon initiation, patients were randomized to the intervention group, and received fluvoxamine 2 times daily for 10 days, or to the placebo group.

The time to sustained recovery served as the primary outcome, and was defined as 3 consecutive days without symptoms. A composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28 was noted as one of the 7 secondary outcomes.

Low-Dose Fluvoxamine Fails to Demonstrate Efficacy

The median age of 1331 randomized patients was 47 years, with slightly more than half the population (57%) made up of women. The majority of patients (67%) reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Of those patients who were randomized, 674 patients in the fluvoxamine group and 614 in the placebo group completed the trial, totaling 1288 patients that were included in the analysis.

The primary outcome, median time to sustained recovery, differed between the groups by 1 day. The cumulative duration of illness in the intervention group was 12 days, and spanned from 11-14 days. The placebo group was 13 days, with a range of 12-13.

Data for the secondary composite outcome, showed 26 patients (3.9%) in the fluvoxamine group were either hospitalized, had an urgent care visit, had an emergency department visit, or died. In the placebo group, this occurred in 23 patients (3.8%).

A total of 3 patients were hospitalized, one from the fluvoxamine group and 2 from the placebo group. Adverse events were uncommon in both groups and no deaths occurred.

“Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery,” investigators concluded. “These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.”

The study "Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19" was published in JAMA.