A handful of studies have suggested that for newly infected COVID-19 patients, risk for serious illness may be reduced with a short course of fluvoxamine (Luvox), a decades-old pill typically prescribed for depression or obsessive-compulsive disorder (OCD). But those were small studies involving just a few hundred people.
This week, researchers reported promising data from a large, randomized phase 3 trial that enrolled COVID-19 patients from 11 sites in Brazil. In this study, in which 1,472 people were assigned to receive either a 10-day course of fluvoxamine or placebo pills, the antidepressant cut emergency department and hospital admissions by 29%.
Findings from the new study, which have not yet been peer reviewed, were published August 23 in MedRxiv.
Around the globe, particularly in countries without access to vaccines, “treatment options that are cheap and available and supported by good-quality evidence are the only hope we’ve got to reduce mortality within high-risk populations,” said Edward Mills, PhD, professor in the department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont.
The new findings came from TOGETHER, a large platform trial coordinated by Dr. Mills and colleagues to evaluate the use of fluvoxamine and other repurposed drug candidates for symptomatic, high-risk, adult outpatients with confirmed cases of COVID-19.
The trial’s adaptive format allows multiple agents to be added and tested alongside placebo in a single master protocol – similar to the United Kingdom’s Recovery trial, which found that the common steroid dexamethasone could reduce deaths among hospitalized COVID-19 patients.
In platform trials, treatment arms can be dropped for futility, as was the case with hydroxychloroquine and lopinavir-ritonavir, neither of which did better than placebo at preventing hospitalization in an earlier TOGETHER trial analysis.
Study details
In the newly reported analysis, patients were randomly assigned to receive fluvoxamine or placebo between January and August 2021. Participants took fluvoxamine 100 mg twice daily for 10 days. By comparison, the U.S. Food and Drug Administration recommends a maximum daily dose of 300 mg of fluvoxamine for patients with OCD; full psychiatric benefits occur after 6 weeks.
For the primary outcome, the investigators assessed whether the conditions of patients with COVID worsened over a 28-day period so as to require either hospitalization or observation in the emergency department for more than 6 hours. In the placebo group, 108 of 733 patients’ conditions deteriorated to this extent (14.7%); by contrast, only 77 of 739 patients in the fluvoxamine group (10.4%) met these primary criteria – a relative risk reduction of 29%.
The treatment effect was greater (34%) in the per protocol analysis of participants who completed their course of pills.
The investigators also collected data on vital signs, including temperature and oxygen saturation, as well as adverse events reported at clinic visits or through video conferencing, phone calls, or social media applications. Side effects were mild, most commonly nausea and fatigue, and did not differ significantly between active treatment and control groups, Dr. Mills said in an interview.
Amid scores of studies evaluating repurposed drugs for COVID-19, the data on fluvoxamine are “looking much more favorable than anyone could have guessed – at least anyone in infectious disease,” said Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
The new TOGETHER trial results augment supportive data published in JAMA last November from a phase 2 randomized trial that was small but “very well done,” Dr. Sax told this news organization.
Those results got a boost from a subsequent study of 65 racetrack workers who chose to take fluvoxamine during a COVID-19 outbreak in the San Francisco Bay area. Forty-eight persons opted against taking the drug. In this small, nonrandomized study, “the people who chose to be treated with fluvoxamine were sicker [at baseline] than the people who didn’t go on it, and yet the [treated group] ended up better,” said Dr. Sax, who discussed accumulating data on the use of fluvoxamine for COVID-19 in a recent New England Journal of Medicine blog post.