An anxiety-fighting drug that has been on the market for decades could turn out to be a potent weapon in the fight against COVID-19.
Early-stage research published in a major journal this month found the antidepressant fluvoxamine may prevent patients with COVID-19 from needing hospital care.
The findings are strong, but preliminary. According to a report in JAMA, no one who took the drug for two weeks soon after being diagnosed with COVID developed serious breathing problems, vs. 8% on a placebo who had shortness of breath and low oxygen levels. The study involved 152 people.
“It was a well-done trial. But it’s still a relatively small number of patients, and that is the only concern,” said Dr. David Boulware, an infectious disease physician and researcher with the University of Minnesota. Boulware is an unpaid adviser on the study’s design.
Doctors say it’s still too soon to add fluvoxamine to the treatment guidelines for symptomatic, recently diagnosed patients who want to stay out of the hospital. No doctor or hospital in the state contacted by the Star Tribune for this story said they’re giving fluvoxamine to COVID patients.
But Minnesotans and people around the country will soon be able to enter the final phase of the clinical trial, where they could get the drug (or a placebo) plus at-home medical equipment and monitoring. The trial is “contactless,” meaning all communications are online, over the phone or through shipping services.
Dr. Eric Lenze, principal investigator for the trial at Washington University in St. Louis, said enrollment for the final phase is likely to start in early December, and physician referral is not needed. People can enroll on a website, similar to the one used for the preliminary phase.
“We not only monitor people, but if they are deteriorating, we let them know what to do,” Lenze said. “In the first study it was quite often us … who told patients to get ahold of their primary care doctor or go straight to the emergency room, because they were deteriorating.”
Since the start of the pandemic in Minnesota, just over 5% of people with diagnosed cases of COVID-19 in the state have been admitted to the hospital for it, and 1.2% required intensive-care beds, often for invasive breathing support.
Just over 1% of all COVID cases confirmed by testing in Minnesota have resulted in death. But the overall death rate is unclear because so many cases are not diagnosed.
On Sunday, the Minnesota Department of Health added 8,946 confirmed and probable cases of the viral respiratory illness, bringing the weekend’s case tally to 17,968.
Since new cases weren’t recorded on Thanksgiving, the weekend’s tally may have been pushed higher by delayed reporting. Officially, the seven-day average stood at more than 6,100 cases per day on Sunday, equivalent to where it stood two weeks ago.
Meanwhile, the state reported 57 new deaths, bringing the number of Minnesotans who have died from the viral respiratory illness to 3,578. Last week the state surpassed an average of 50 deaths per day for the first time.
More than 16,400 Minnesotans have been hospitalized for COVID.
Preventing patients from needing hospitalization is the primary goal in examining antidepressants like fluvoxamine.
While some of the world’s most powerful biomedical companies are trying to engineer new drugs for COVID-19, like the much-discussed monoclonal antibody infusions, researchers like Lenze are working to see whether medicine already in stock at your local pharmacy could have an impact.
“This is a strategy for drug resurfacing,” Lenze said. “Take something that is already widely available and known to be safe and easy to use, and inexpensive, and see if it’ll work for something new.”
Selective serotonin reuptake inhibitors (SSRIs) like fluvoxamine work by releasing molecules that bind to receptors in the central nervous system that affect mental health. Fluvoxamine binds to sigma-1 receptors, which also affect immune response that can damage the lungs of COVID patients.
Generic fluvoxamine is normally prescribed for obsessive-compulsive disorder and generalized anxiety, and its adverse effects are similar to other SSRIs, including headaches, nausea, diarrhea, restlessness and fatigue, said Jen Marquart, clinical pharmacy manager at North Memorial Health.
“If found effective in treating COVID-19, the benefits may well outweigh the downsides” of the drug, Marquart said in an e-mail. The trial will use a 15-day course of treatment, making any adverse effects more palatable than during a much longer treatment for mental health issues.
A course of the generic drug for COVID costs about $12.
But doctors and spokesmen with North Memorial, Mayo Clinic and HealthPartners all said more study is needed before they would use fluvoxamine for treating symptomatic COVID patients outside the hospital.
Such skepticism from the medical establishment frustrates tech entrepreneur Steve Kirsch, who founded the COVID-19 Early Treatment Fund (CETF) earlier this year to accelerate research into existing drugs, which he says is the fastest and most efficient way to end the pandemic.
He believes the initial trial results on fluvoxamine published in JAMA were so positive and clear that waiting several more months for the final trial results will needlessly sacrifice lives.
“It’s crazy that this drug is not getting front-and-center attention,” Kirsch said. CETF has approved $266,000 in grants for the fluvoxamine trials.
JAMA editors say the fluvoxamine paper presents preliminary findings. Out of more than 10,000 submissions related to COVID-19, the journal opted to publish the fluvoxamine paper because the study was designed to minimize bias while keeping all patient interactions remote.
“I think the contactless design is unique, innovative and a great model for doing randomized trials in a pandemic,” said Dr. Christopher Seymour, a Pittsburgh physician and JAMA associate editor.
The trial is randomized and double-blind, which means patients are randomly assigned the real drug or a placebo, and neither the researchers nor the patients know who’s getting which one until the end.
Hard to be accepted
Most who try to enroll will probably not make the cut.
In the first study, fewer than 20% of people who applied made it past the screening stage, primarily because they already had been hospitalized, had symptoms more than seven days previously, or had no symptoms. The study excluded those with lung disease, heart failure or immunocompromised conditions.
Unlike the preliminary study, the final phase will specifically recruit people at risk for serious COVID complications. To be included, participants will have to have at least one risk factor, such as being 40 or older. The goal is to enroll more than 800 people this time.
Boulware, the U doctor who ran a similar outpatient trial that found the drug hydroxychloroquine did not stop the worsening of COVID-19 after exposure, said he hopes the fluvoxamine trial will quickly lead to definitive answers.
“If I got COVID, I would want to enroll in this trial,” he said.