Summary: A new small scale study reveals the antidepressant fluvoxamine may be a new tool in the fight against COVID-19. Researchers report fluvoxamine reduced the severity of coronavirus symptoms and hospitalizations.

Source: University of Virginia

The antidepressant fluvoxamine appears to prevent COVID-19 infections from worsening and may help keep patients out of the hospital, a trial based on research from the University of Virginia School of Medicine suggests.

The clinical trial, conducted by the Washington University School of Medicine in St. Louis, compared fluvoxamine with a placebo in 152 adult outpatients infected with the coronavirus. None of the participants who received fluvoxamine saw “clinical deterioration” after 15 days, while six patients who received placebo did. Of those six, four were hospitalized, for periods ranging from four to 21 days. One was on a ventilator for 10 days.

While the study size was small, the researchers say the results are statistically significant and that fluvoxamine warrants further study as a COVID-19 treatment. They plan to launch a larger trial in the next few weeks.

“The patients who took fluvoxamine did not develop serious breathing difficulties or require hospitalization for problems with lung function,” said Eric J. Lenze, MD, of the Washington University School of Medicine. “Most investigational treatments for COVID-19 have been aimed at the very sickest patients, but it’s also important to find therapies that prevent patients from getting sick enough to require supplemental oxygen or to have to go to the hospital. Our study suggests fluvoxamine may help fill that niche.”

Fluvoxamine and COVID-19

The Washington University researchers launched the randomized, double-blind trial based on a discovery by UVA’s Alban Gaultier, PhD, and former graduate student Dorian A Rosen, PhD. Gaultier and Rosen found last year that fluvoxamine may stop the deadly inflammation known as sepsis, in which the immune response spirals out of control. The drug, they determined, reduced the production of cytokines, which have been linked to potentially deadly “cytokine storms” thought to occur in severe cases of COVID-19.

That connection prompted the Washington University team to investigate the possibility that fluvoxamine could have a protective effect for patients with COVID-19. Perhaps, they thought, the drug could help prevent the immune system overreactions triggered by this strange new coronavirus. And their work suggests it may.

“Because elevated cytokines levels have been associated with COVID-19 severity, testing fluvoxamine in a clinical trial made a lot of sense to us,” said Gaultier, of UVA’s Department of Neuroscience and its Center for Brain Immunology and Glia (BIG). “We are still unclear about the mode of action of fluvoxamine against SARS-CoV-2, but research is under way to find the answer.”

The Washington University team noted that recent research has raised questions about whether cytokines are really playing important roles in COVID-19 deaths. If not, the researchers say, fluvoxamine may be having beneficial effects by some other mechanism not yet understood.

“There are several ways this drug might work to help COVID-19 patients, but we think it most likely may be interacting with the sigma-1 receptor to reduce the production of inflammatory molecules,” said Washington University’s Angela M Reiersen, MD. “Past research has demonstrated that fluvoxamine can reduce inflammation in animal models of sepsis, and it may be doing something similar in our patients.”

While the study size was small, the researchers say the results are statistically significant and that fluvoxamine warrants further study as a COVID-19 treatment. Image is in the public domain

The researchers stressed that there were several limitations to their research. In addition to its small size, the trial was hampered by other factors, including that 20% of participants stopped answering surveys during the 15-day trial. (The researchers determined that none of those participants required hospitalization or emergency-department visits, but they could not rule out that the participants sought treatment elsewhere, such as at urgent-care clinics.)

Because of these limitations, the researchers say that the trial’s results should not be treated as a measure of fluvoxamine’s effectiveness against COVID-19 but as an encouraging indicator that the drug warrants further testing.

“If a larger clinical trial (phase III) confirms the results, fluvoxamine would be a perfect treatment for COVID patients newly diagnosed,” Gaultier said. “Fluvoxamine is not an experimental drug, it is cheap and safe and could be available as a first line of defense to unburden the hospitals that are overwhelmed by the COVID health crisis.”

Funding: The clinical trial was supported by the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University and the COVID-19 Early Treatment Fund. Additional support was provided by the Center for Brain Research in Mood Disorders at Washington University, the Bantly Foundation and National Institutes of Health grant UL1TR002345.

About this COVID-19 research news

Source: University of Virginia
Contact: Josh Barney – University of Virginia
Image: The image is in the public domain

Original Research: Open access.
“Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients WithSymptomatic COVID-19: A Randomized Clinical Trial” by Eric J. Lenze, MD; Caline Mattar, MD; Charles F. Zorumski, MD; Angela Stevens, BA; Julie Schweiger; Ginger E. Nicol, MD; J. Philip Miller, AB; Lei Yang, MPH, MSIS; Michael Yingling, MS; Michael S. Avidan, MBBCh; Angela M. Reiersen, MD, MPE. JAMA


Abstract

Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients WithSymptomatic COVID-19: A Randomized Clinical Trial

Importance  

Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production.

Objective  

To determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease.

See also

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Design, Setting, and Participants  

Double-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020.

Interventions  

Participants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days.

Main Outcomes and Measures  

The primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.

Results  

Of 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) 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 (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events.

Conclusions and Relevance  

In this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.

Trial Registration  

ClinicalTrials.gov Identifier: NCT04342663



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