From the Journals

Antidepressant shows early promise for mild COVID-19


Early treatment with the antidepressant fluvoxamine (Luvox) may help prevent respiratory deterioration in patients with mild symptomatic COVID-19, results of a preliminary randomized controlled trial suggest.

In the trial, none of the patients who took fluvoxamine within 7 days of first symptoms developed serious breathing difficulties or required hospitalization for respiratory deterioration.

Dr. Eric J. Lenze

“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,” study investigator Eric J. Lenze, MD, professor of psychiatry and director of the Healthy Mind Lab at Washington University, St. Louis, said in a statement.

“Our study suggests fluvoxamine may help fill that niche,” Lenze added.

The study was published online Nov. 12 in the JAMA.

Antiviral effects?

The study included 152 nonhospitalized adults (mean age, 46 years; 72% women) with confirmed SARS-CoV-2 infection and mild COVID-19 symptoms starting within 7 days and oxygen saturation of 92% or greater.

Eighty were randomly assigned to 100 mg of fluvoxamine three times daily for 15 days and 72 to matching placebo.

The primary outcome was clinical deterioration within 15 days of randomization defined by meeting two criteria. These included shortness of breath or hospitalization for shortness of breath or pneumonia and oxygen saturation <92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.

Clinical deterioration occurred in none of the 80 patients taking fluvoxamine compared with 6 of 72 (8.3%) patients taking placebo, an absolute difference of 8.7% (95% confidence interval, 1.8%-16.4%).

Clinical deterioration in the placebo group happened from 1 to 7 days after randomization and from 3 to 12 days after the onset of COVID-19 symptoms. Four of the 6 patients with clinical deterioration were admitted to the hospital for 4-21 days. One patient required mechanical ventilation for 10 days. No patients died.

Hypothesis generating

The authors cautioned that the study was small and with short follow-up and that the findings “need to be interpreted as hypothesis generating rather than as a demonstration of efficacy.”

However, they noted, if the drug turns out to be effective for COVID-19, the potential advantages of fluvoxamine for outpatient use include its safety, widespread availability, low cost, and oral administration.

Carolyn Machamer, PhD, member of the COVID-19 Early Treatment Fund (CETF) scientific advisory board, which funded the study, noted that there are several reasons fluvoxamine might be helpful in COVID-19.

“The preliminary data suggest the mechanism involves activation of the sigma-1 receptor, which has a number of documented activities. One strong possibility is that activation dampens cytokine release and thus the inflammatory response,” she said in an interview.

“Other possible mechanisms can include inhibition of platelet activation and modulation of autophagy. Coronaviruses usurp some autophagy machinery to remodel membranes for replicating their genomes, so this last mechanism might actually be antiviral,” said Dr. Machamer.

She added that a much larger trial is “crucial to see if the initial striking results can be reproduced, and the Healthy Mind Lab and CETF are currently coordinating these next steps.”

The editors of JAMA published an “Editor’s Note” with the study. In it, they wrote the pilot study addresses a “critically important question during the pandemic of how to prevent individuals who acquire COVID-19 from deteriorating to serious illness. If an effective treatment is found for this key gap in treatment, it will affect the health of millions of people worldwide.”

However, the study has “important limitations, and the findings should be interpreted as only hypothesis generating; they should not be used as the basis for current treatment decisions,” cautioned authors Christopher Seymour, MD, Howard Bauchner, MD, and Robert Golub, MD.

This study was supported by the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University and the CETF. Additional support was provided by the Center for Brain Research in Mood Disorders at Washington University, the Bantly Foundation, and the National Institutes of Health.

Dr. Lenze has received grants from the Patient-Centered Outcomes Research Institute, Takeda, Alkermes, Janssen, Acadia, and the Barnes Jewish Hospital Foundation and has received consulting fees from Janssen and Jazz Pharmaceuticals. Dr. Machamer has disclosed no relevant financial relationships. Dr. Seymour has received grants from the National Institutes of Health and personal fees from Beckman Coulter and Edwards Lifesciences.

A version of this article originally appeared on

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