Summary: A small randomized trial suggests the antidepressant fluvoxamine may reduce the risk of clinical deterioration and hospitalization for people with early, symptomatic COVID-19.
Source: University of Virginia
Overview
A preliminary clinical trial indicates that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) commonly used as an antidepressant, may help prevent mild COVID-19 from progressing to more severe disease. Researchers found fewer cases of clinical deterioration and reduced hospital admissions among outpatients who received fluvoxamine compared with those who received placebo.
The randomized, double-blind study enrolled 152 adult outpatients with confirmed SARS-CoV-2 infection and symptom onset within seven days. Participants were assigned to receive either fluvoxamine or placebo three times a day for 15 days and were followed remotely. In the fluvoxamine group none of the patients experienced the trial’s predefined clinical deterioration within 15 days, while six patients in the placebo group did. Of those six, four required hospitalization, and one needed ventilatory support for 10 days.
Although the sample size was limited, the difference reached statistical significance, prompting the authors to call for larger phase III trials to confirm these findings and to better define fluvoxamine’s potential role in early COVID-19 treatment.
Fluvoxamine and COVID-19
This trial was inspired by laboratory research from the University of Virginia showing that fluvoxamine can reduce excessive inflammatory responses in sepsis models. That work found the drug lowered production of cytokines—signaling proteins implicated in severe inflammatory reactions, sometimes called “cytokine storms,” which are associated with poor outcomes in some COVID-19 cases. Based on those findings, investigators hypothesized that fluvoxamine might blunt harmful immune overreactions in early SARS-CoV-2 infection and thereby prevent progression to severe disease.
Researchers caution that the exact mechanism by which fluvoxamine may protect patients with COVID-19 is not yet established. One plausible pathway involves the drug’s interaction with the sigma-1 receptor, which can regulate inflammatory signaling. However, other mechanisms could be responsible, and active research is ongoing to clarify how fluvoxamine affects viral illness and immune responses.
Trial design and key outcomes
The Washington University School of Medicine in St. Louis conducted the double-blind, randomized, fully remote trial. Eligible participants were community-dwelling adults with laboratory-confirmed SARS-CoV-2 infection, oxygen saturation of 92% or greater, and symptom onset within seven days. From April to August 2020, 152 participants from the St. Louis region were enrolled and followed through mid-September.
Participants received either 100 mg of fluvoxamine or matching placebo three times daily for 15 days. The primary outcome was clinical deterioration within 15 days, defined as both increased shortness of breath or hospitalization for respiratory illness and oxygen saturation below 92% on room air or the need for supplemental oxygen to reach 92% or greater.
Among the 152 randomized participants (mean age 46; 72% women), 115 completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group, a statistically significant difference in survival analysis. The fluvoxamine group reported fewer serious adverse events (one) than the placebo group (six), with a similar rate of other adverse events between groups.
Limitations and next steps
The investigators emphasize several limitations: the trial’s small size, the relatively short follow-up period, and incomplete data from about 20% of participants who stopped responding to surveys during the 15-day follow-up. While the trial team found no evidence that those nonresponders required hospitalization or emergency care, they could not completely rule out treatment sought at other sites such as urgent-care clinics.
Because of these constraints, the results should be viewed as preliminary and hypothesis-generating rather than definitive proof of efficacy. The authors plan larger randomized trials to confirm whether fluvoxamine reliably reduces clinical deterioration, hospitalizations, and more severe respiratory outcomes when given early in symptomatic COVID-19.
If confirmed in larger phase III studies, fluvoxamine could represent an inexpensive, widely available treatment option for people newly diagnosed with COVID-19. As a drug that is already approved for other uses, fluvoxamine would not require the same development timeline as an entirely new medication, potentially allowing rapid deployment as an early intervention to reduce the burden on hospitals.
Funding and disclosures
The trial received support from the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University, the COVID-19 Early Treatment Fund, the Center for Brain Research in Mood Disorders at Washington University, the Bantly Foundation, and NIH grant UL1TR002345.
About this COVID-19 research news
Source: University of Virginia
Contact: Josh Barney – University of Virginia
Image: Image in the public domain
Original research: JAMA article titled “Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial” by Eric J. Lenze, MD, and colleagues. Open access publication.
Abstract (condensed)
Importance: COVID-19 can provoke an excessive immune response that contributes to severe illness. Fluvoxamine may limit clinical deterioration by modulating the sigma-1 receptor and cytokine production.
Objective: To test whether fluvoxamine, administered early in mild COVID-19, prevents clinical deterioration and reduces disease severity.
Design: Double-blind, randomized, fully remote clinical trial of fluvoxamine versus placebo in nonhospitalized adults with confirmed COVID-19 and recent symptom onset. Primary outcome: clinical deterioration within 15 days, defined by worsening respiratory symptoms combined with low oxygen saturation or need for supplemental oxygen.
Results: In this preliminary sample (n=152), clinical deterioration occurred in 0 of 80 participants randomized to fluvoxamine versus 6 of 72 randomized to placebo. The difference was statistically significant, but the study’s small size and limited follow-up mean larger trials are needed to determine clinical efficacy.
Trial registration: ClinicalTrials.gov identifier NCT04342663 (registration number provided for reference).