A cheap antidepressant lowers the risk of Covid hospitalization, a large study finds.

A large clinical trial has found that a common and inexpensive antidepressant lowered the odds that high-risk Covid-19 patients would be hospitalized. The results, published on Wednesday, could open the door to new guidelines for the drug’s use both in the United States and globally.

The drug, fluvoxamine, has been safely prescribed for nearly 30 years as a treatment for obsessive-compulsive disorder. But when the coronavirus started spreading, researchers were drawn to the medication because of its ability to reduce inflammation, potentially allowing it to quell the body’s overwhelming response to a coronavirus infection.

Several smaller studies of fluvoxamine earlier in the pandemic showed promising results, but none was as large or persuasive as the one published on Wednesday by a group of researchers in Canada, the United States and Brazil, outside scientists said. Among nearly 1,500 Covid patients in Brazil given either fluvoxamine or a placebo, the drug reduced the need for hospitalization or prolonged medical observation by one-third, the study found. It was published in The Lancet Global Health.

Some patients struggled to tolerate the drug and stopped taking it, the study said, raising a question among outside scientists about whether they had yet identified the ideal dose. But among those who had largely followed doctors’ orders, the benefits were even more striking. In those patients, the drug reduced the need for hospitalization by two-thirds and slashed the risk of dying: One Covid patient given fluvoxamine died, compared with 12 given a placebo.

“That’s really good,” said Dr. David Boulware, an infectious disease scientist at the University of Minnesota who worked on a smaller, real-world study of the drug in Covid patients in California. Plus, he added, “it’s not a shiny new, expensive drug. The nice thing about this is it has a known safety profile.”

Beyond proper dosing, the study left other questions unresolved, scientists said. Penny Ward, a visiting professor in pharmaceutical medicine at King’s College London, noted that part of the drug’s benefit appeared to come from reducing the need for extended medical observation, which the study tracked alongside hospital admissions. And most patients in the study were unvaccinated, Professor Ward said, so it’s unclear how well the drug would work in the vaccinated.

The new study, coming nearly a year after smaller trials of the drug, was a reminder of the difficulty that many researchers have had running large tests of Covid treatments. The Biden administration has made more funding available for such trials, scientists said, but enrolling enough patients has only gotten more difficult: Most high-risk Americans are vaccinated, and vaccine-averse people may be less likely to participate in trials.

Because fluvoxamine is already approved for treating O.C.D., doctors can already prescribe it “off label” for Covid. But Dr. Boulware said that prescriptions of the drug had increased only slightly during the pandemic, unlike other repurposed drugs with far less scientific support, like hydroxychloroquine and ivermectin.

“It hasn’t really gotten any cult following,” he said.

Federal treatment guidelines say that larger trials are necessary to evaluate the use of fluvoxamine for Covid, and scientists said they expected those recommendations to change on the basis of the new study.

The new findings are also expected to boost the popularity of the drug in less wealthy countries: A 10-day course of the drug costs about $4.