A pill ordinarily prescribed to treat obsessive compulsive or anxiety disorder prevented symptoms of nonhospitalized Covid-19 patients from worsening compared to placebo, a small randomized controlled trial concludes, suggesting the drug’s immune-modulating effects could be further explored as a treatment for the disease.
The authors say their results, published Thursday in JAMA, fall short of demonstrating efficacy because the study was so small and looked at relatively few measures of illness. But experts say the idea merits further study in a larger group of patients.
Researchers from Washington University in St. Louis divided 152 patients diagnosed with Covid-19 in the previous seven days into two groups. Eighty were given fluvoxamine — a kind of antidepressant known as an SSRI that also has a strong effect on inflammation — and 72 patients got a placebo. After 15 days, none of the patients who got the drug saw symptoms deteriorate — defined as shortness of breath and lower oxygen saturation — but six of the patients on placebo did get worse. Four of them were hospitalized and one required a ventilator to breathe. That 8.3% deterioration rate in the placebo group is considered statistically significant.
Nahid Bhadelia, an infectious disease physician at Boston University, would also like to see the preliminary data lead to larger trials and a better understanding of the possible biological mechanisms at work.
“It seems like a lot of antiviral candidates have shown limited or early benefit only, which has really highlighted for me how much of severe disease is immune driven,” she told STAT. “An outpatient medication that is oral and reduces progression to disease would be a great addition to our arsenal.”
Antiviral monoclonal antibodies, such as Eli Lilly’s bamlanivimab, which received emergency use authorization this week, are IV medications. They may help, Bhadelia said, “but the infusion aspect makes it more cumbersome to make available to a large group of people. An oral candidate could help bridge access and equity issues if larger trials show efficacy.”
Previous studies have shown that fluvoxamine dampens the inflammatory response during sepsis, an overwhelming infection. The drug stimulates an immune receptor that controls how much cytokine is produced. “Cytokine storms” have been blamed for triggering severe cases of Covid-19, as part of an overreactive immune response worse than the coronavirus it seeks to destroy, although recent research has cast a shadow on that interpretation. The new study’s authors cite a recent report, for example, that found lower levels of cytokines in patients with severe Covid-19 versus patients with bacterial sepsis.
Their fluvoxamine study was conducted remotely, with the drug or placebo and other supplies delivered to patients’ homes, including thermometers and devices to check their blood pressure and oxygen saturation. Patients reported their oxygen saturation, vital signs, whether they took their medications, and how their Covid-19 symptoms felt by phone or internet.
In each group, about 70% were white, about one-quarter were Black, and the other people were Asian or their race was unknown.
Eric Topol, director of the Scripps Research Translational Institute, called the study an interesting one looking at a drug that hasn’t received much attention, a putative immune response modulator.
“The good part is that it was tested for early illness, for which we have nothing except potentially monoclonal antibodies,” he told STAT. “The encouraging results are countered by multiple limitations (as the authors appropriately acknowledged) so I’d say it is now a candidate drug intervention seeking a real, larger, rigorous randomized trial.”
Steven Nissen, a cardiologist at the Cleveland Clinic, said he is “moderately skeptical” of the small study with self-reported outcomes, underscoring the limitations listed in the study itself. “It is statistically fragile. Extremely fragile,” he told STAT.
In an editor’s note explaining why JAMA chose to publish the preliminary study, the editors said they were convinced by the double-blind, placebo-controlled, randomized design of the study — the gold standard in medical research — as well as the dearth of options while the world waits for Covid-19 vaccines.
“What about treatments for patients with COVID-19 who are neither hospitalized nor severely ill?” they wrote. “If an effective treatment is found for this key gap in treatment, it will affect the health of millions of people worldwide.”