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Clinical deterioration was not seen in 80 symptomatic COVID-19 patients who received the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in a randomized trial, compared with six of 72 receiving placebo.

That translated to an absolute difference in risk of 8.7 percentage points (95% CI 1.8-16.4), reported Eric Lenze, MD, of Washington University School of Medicine in St. Louis, Missouri, and colleagues.

More patients in the placebo group also experienced adverse events versus the intervention group, the authors wrote in a preliminary communication in .

An by JAMA associate editor Christopher Seymour, MD, of the University of Pittsburgh, and colleagues (including JAMA editor Howard Bauchner, MD) characterized this as a "pilot study" representing preliminary evidence, and cautioned readers that the findings should be interpreted as "hypothesis generating."

But out of the more than 10,000 COVID-19 submissions they have received since February 2020, most were rejected. They published this one, they said, in part because it was a "double-blind, placebo-controlled, randomized clinical trial, which is generally considered a design that minimizes bias and can support causal inference," though they emphasized more confirmatory data are needed from larger trials.

They also noted the study's unique design: a "remote" trial with "no direct contact with self-quarantined participants," with data collected through patient self-report and phone interviews.

"Although these individual components are part of other trials, in the current trial they are combined into a contactless design to protect both participants and researchers during a pandemic," the editors wrote.

Lenze and colleagues noted that lung damage from COVID-19 is due to excessive inflammatory response, and a potential mechanism for immune modulation is sigma-1 receptor (S1R) agonism. They noted that previous studies found fluvoxamine, an SSRI and S1R agonist used to treat some forms of obsessive-compulsive disorder and social anxiety disorder, helped to reduce damaging aspects of the inflammatory response during sepsis in preclinical models.

The study was conducted from April 10 to August 5 in the St. Louis metropolitan area. It was "contactless" because each participant received the assigned medication, oxygen saturation and blood pressure monitors, and thermometer in a packet at his or her door. Patients took their own vital signs, and staff called them to inform them when to take the study medication. Data collection was done via twice-daily email surveys, with phone calls as backup, and patients reported their oxygen saturation, vital signs, medication adherence, and COVID-19 symptoms.

Participants were eligible if they were non-hospitalized adults with SARS-CoV-2 infection confirmed via PCR assay, were symptomatic within the first 7 days of the first dose of study medication, and had an oxygen saturation of 92% or greater.

Fluvoxamine was dosed at 50 mg for the first day, then 2 days at 100 mg twice daily as tolerated, and 100 mg daily three times a day as tolerated through day 15. The primary endpoint was clinical deterioration within 15 days. This outcome was defined as presence of dyspnea or hospitalization for shortness of breath or pneumonia, decrease in oxygen saturation below 92% on room air, or supplemental oxygen required to maintain oxygen saturation of 92% or greater.

Of the six placebo patients who deteriorated, four were hospitalized, with length of stay ranging from 4-21 days and one patient required mechanical ventilation for 10 days. No patients died.

However, 18 participants in the fluvoxamine group stopped responding to surveys prior to day 15 as did 19 patients in the placebo group.

There was one serious adverse event reported in the intervention group, while six serious adverse events and 12 other adverse events were reported in the placebo group. Pneumonia and gastrointestinal symptoms occurred more often in the placebo group.

Lenze and colleagues said that the underlying mechanism of why fluvoxamine was effective would need "further clarification," but noted it is widely available, low cost, can be administered orally to outpatients, and does not promote QT prolongation. However, it does have adverse events and can cause drug-drug interactions, they added.

Limitations to the study include its small sample size and geographic area, the small number of endpoint events, and that the differences in clinical deterioration may be more due to "comparative baseline distributions of oxygen saturation rather than an effect of treatment."

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