Leonard Imbula of the Healthy Mind Lab at Washington University School of Medicine in St. Louis holds a vial of fluvoxamine, a psychiatric medicine that has been found, in a pair of studies conducted on two continents, to be an effective treatment for persons suffering from COVID-19.
In the largest study yet to evaluate a common, low-cost antidepressant as a treatment for COVID-19, researchers from Washington University School of Medicine in St. Louis and from Canada and Brazil have found that the drug fluvoxamine prevents some of the most serious complications of COVID-19, sharply reducing the risk of hospitalization and death.
The study’s results were published recently in the journal The Lancet Global Health.
This experiment, done in Brazil, supports results from the first trial of fluvoxamine for COVID-19, which was initiated in early 2020 and headed by Eric J. Lenze, MD, and Angela M. Reiersen, MD, both psychiatrists from the School of Medicine. Results of that trial were published in JAMA one year ago. The two were interested in the antidepressant because of its anti-inflammatory qualities. They also are co-authors of the current study.
The Brazilian study monitored roughly 1,500 patients newly diagnosed with COVID-19. Of these, 741 patients received the medicine — a 100 mg tablet of fluvoxamine twice a day for 10 days — while 756 received a placebo twice daily. The trial was ended early because those taking the fluvoxamine saw substantially better outcomes than those taking a placebo.
Of individuals using fluvoxamine, 11 percent became unwell enough to necessitate an extended stay at a COVID-19 emergency center or be admitted to a hospital, compared with 16 percent of people who received a placebo.
In a secondary analysis of participants who took at least 80 percent of their pills, the findings were even more striking: Risk of hospitalization or extended emergency care was reduced by two-thirds, and there was one death among those taking fluvoxamine compared with 12 deaths in the placebo group, a reduction in mortality risk of 91 percent.
“Based on this replication of our findings in such a large study, we believe fluvoxamine should be considered as a treatment for patients at high risk for serious illness or death,” said Lenze, the Wallace and Lucille Renard Professor of Psychiatry and director of the Healthy Mind Lab at Washington University. “In contrast to other therapies being developed to treat COVID-19, this drug has a long and well-established track record of safety, and doctors may choose to prescribe it off-label for COVID-19 right away,” the researchers write.
Lenze said vaccines are exceptionally good at preventing major sickness but that many countries have had problems vaccinating their residents, and even some vaccinated persons may still be at risk for serious COVID-19 symptoms owing to underlying medical illness or decreasing immunity over time. Fluvoxamine is a low-cost treatment alternative for newly diagnosed patients and looks to be highly effective in lowering severe disease.
“As COVID-19 spread rapidly around the globe, there have been many attempts to repurpose existing drugs that might have anti-viral and/or anti-inflammatory effects; fluvoxamine is the only drug in this category that has shown promising efficacy to date,” said David H. Perlmutter, MD, executive vice chancellor for medical affairs and the George and Carol Bauer Dean of Washington University School of Medicine in St. Louis. “It is truly remarkable ingenuity on the part of the Drs. Reiersen and Lenze team to have developed the original hypothesis for testing this drug, as well as the rapid deployment methods used for the initial clinical trial. But perhaps most importantly, the results point us in the direction of a safe and inexpensive oral agent that can be used to reduce hospitalizations and save lives.”
Unlike newer antiviral medications that are allegedly promising against COVID-19, fluvoxamine would not require emergency use authorization before it could be prescribed. That’s because it already is licensed by the U.S. Food and Drug Administration for the treatment of obsessive-compulsive disorder (OCD) and has been given for more than three decades to treat OCD, anxiety disorders, and depression. It belongs to a class of medications called selective serotonin reuptake inhibitors (SSRIs) (SSRIs). But unlike other SSRIs, fluvoxamine interacts strongly with the sigma-1 receptor, a protein inside cells that helps regulate the body’s inflammatory response.
“We believe this drug most likely is interacting with the sigma-1 receptor to reduce the production of inflammatory molecules in the body,” said Reiersen. “When it comes to the treatment of psychiatric illness, this represents an interesting distinction from other SSRIs; however, it appears to be critical to fluvoxamine’s effects in patients with COVID-19.”
The latest findings come from research known as the TOGETHER Trial — a big, adaptive platform trial that has randomized more than 4,000 patients worldwide into studies examining existing medications for their ability to effectively treat COVID-19. Fluvoxamine is the first one of the prospective treatments to be deemed successful.
“And it costs about $4 for a course of treatment, so it also can be cost-effective, unlike other, newer COVID-19 therapies,” Lenze said. “The method may be particularly beneficial in countries where vaccination rates are still low.”
The study’s principal author, Edward J. Mills, Ph.D., who is a professor of health research techniques, evidence, and effect at McMaster University in Hamilton, Ontario, said it is crucial to get the medicine out to hard-hit countries as quickly as possible. Mills, also a vice president and senior principal scientist at Cytel, a business that creates statistical software and delivers analytics for clinical studies, termed fluvoxamine one of the finest strategies available to decrease the hazard for persons infected with COVID-19 around the world.