The idea that a drug isn’t specifically an antiviral is no reason to discount its worth in fighting against COVID-19 or any other disease. After all, the biggest change in death rates between the first and second wave of COVID-19 came from the widespread use of steroids to control inflammation and make intubation and other forms of breathing assistance more tolerable.
Hydroxychloroquine first got onto the radar not because of Trump, but because it was one of a group of drugs (disease-modifying antirheumatic drugs) thought to be capable of modifying the communications between cells and the immune system. There were similar anecdotal reports of effectiveness against other diseases, and testing it made sense. What didn’t make sense was Trump standing up to tout the drug as a “miracle” before the data was in—because when that data came in, it showed no positive effect.
In the case of fluvoxamine, it was pulled into COVID-19 studies not because there was thought to be a mechanism by which it would kill the virus, but because it’s one of a group of drugs known as “selective serotonin reuptake inhibitors.” These drugs recently came to the attention of researchers looking at disease treatment after a 2012 study showed that their actual mechanism of action was by lowering inflammation. Inflammation has a strong association with depression—even if the why of that connection isn’t completely understood. But because SSRIs fight inflammation, fluvoxamine is one of several such drugs that have been tested for effectiveness in fighting the symptoms of COVID-19.
The November 2020 issue of the Journal of the American Medical Association contained the results of a small randomized trial conducted by Washington University in St. Louis. The study looked at 152 adults with symptomatic COVID-19, 72 of whom were given placebo rather than fluvoxamine. And the results were good:
Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group.
This was a double-blind, placebo-controlled study—which is about as good as things get on that front. However, the authors acknowledge that “the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.” Because of the date of the trial, none of those involved was vaccinated, and none had been exposed to the delta variant. Washington University began a more extensive trial targeting 1,100 patients last December as part of the broader STOP COVID2 effort.
Fortunately, there already is a larger study. Because another study was recently published in the British medical journal Lancet.
That study was also a placebo-controlled, randomized trial. But this one involved 1,497 patients in Brazil, 741 patients of whom got fluvoxamine and and 756 who received a placebo. The Brazil study also helped to address the other issue mentioned by the St. Louis researchers in that they extended the length of the study to 28 days after the drug (or placebo) was first administered.
Interpretation of the results from the trial were a bit more complex than those in the St. Louis group as the patients were all considered to be at high risk for significant complications, all of them were unvaccinated, and some members began treatment while already experiencing severe symptoms. The term “hospitalized” was also a bit different than in other studies as it included any patient treated for over six hours in an ER or specialized COVID center as well as those admitted with severe symptoms.
But the end results were this: Patients who who received a full 8-10 day course of treatment had a 66% lower rate of hospitalization when compared to placebo. The reduction in deaths among this group was 91%.
Even the study in Brazil still isn’t large enough to determine the real value of fluvoxamine in treating COVID-19. For one thing, a significant portion of the patients didn’t complete the full course (those patients saw about a one-third drop in hospitalizations). Neither the St. Louis nor the Brazil study was sufficient to determine the best time to begin treatment, the best dosage, or long-term consequences. But all of that may be derived when full data from the U.S. and Canadian arms of STOP COVID2 come in.
Fluvoxamine, like other SSRIs, does have potential side effects. It can actually make depression worse, as well as causing unpleasant effects like nausea and sweating. Antidepressants in this class are not addictive, but people who take them for a long period can still suffer from withdrawal when stopping—though that shouldn’t be a problem when taken for only a few days. It’s been around since the 1990s, it’s be prescribed to tens of millions of patients, and the interactions and side effects are generally well understood.
Should the results seen so far hold up, fluvoxamine holds promise not just as a cheap alternative to the antivirals being marketed by Merck and Pfizer, but possibly as the best option to keep a patient in the early stages of COVID-19 infection from dying.