- A growing body of evidence suggests that taking a common antidepressant can help minimize the severity of symptoms and death associated with SARS-CoV-2 infection.
Patients on selective serotonin reuptake inhibitors (SSRIs) had an 8% lower risk of dying from COVID-19 in an observational trial.
Those who took fluoxetine or fluvoxamine had a 26% lower risk of death. - Phase 3 clinical trials are required to evaluate if researchers can reproduce these findings on a big scale.
Several medications have shown promise in the search for COVID-19 therapies. Many people are hailing the two oral antivirals, Molnupiravir from Merck and Paxlovid from Pfizer, as the panaceas for the pandemic. However, uncertainties about their efficacy and safety remain, so the hunt for safe and effective treatments continues.
An observational study has now found that several of the most commonly prescribed antidepressants may help to lower the severity of COVID-19 as well as the disease’s mortality.
A retrospective cohort analysis of 83,584 people with a COVID-19 diagnosis was conducted by researchers from the University of California and Stanford University School of Medicine. They discovered that people who used SSRIs had a decreased risk of dying compared to those who did not.
SSRIs are used by 13.2% of adults (17.7% of women) in the United States. The following drugs belong to this category:
- citalopram (Celexa)
- escitalopram (Lexapro)
- fluoxetine (Prozac, Sarafem)
- fluvoxamine (Luvox)
- paroxetine (Paxil)
- sertraline (Zoloft)
This study contributes to the body of knowledge about the effects of SSRIs gathered from earlier research. Fluvoxamine use was linked to a lower risk of clinical deterioration following SARS-CoV-2 infection in three clinical trials, one of which was just published this month.
“I would call it very provocative. said Dr. William Schaffner, Professor of Infectious Diseases at Vanderbilt University Medical Center in Nashville, Tennessee. It is a large ecological study that builds on previous information suggesting that this class [of drugs] may actually have a role in treating [SARS-CoV-2] infections.”
Reduced mortality
3,401 people were using SSRIs when the study was conducted, according to the findings published in JAMA Network Open. The researchers matched patients with 6,802 non-SSRI controls for sociodemographic factors, medical comorbidities, and pharmaceutical indication.
When compared to the control group, the SSRI group had an 8 percent lower mortality rate (RR). The reduction was largest in those taking fluoxetine (RR of 28%) and fluvoxamine or fluoxetine (RR of 28%). (26 percent ). Other SSRIs did not have the same impact.
“These results confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants […] could be beneficial against COVID-19.”
– Dr. Nicolas Hoertel, M.D., M.PH., Ph.D., writing in an accompanying editorial.
Familiar drugs
One advantage of SSRIs over newer treatments, such as the antivirals being developed by scientists, is that they have been in use for a long time and their negative effects are well known.
“Familiarity, a certain comfort level, is a great advantage. Even though the vaccines have been used in millions of people, one of the first things a vaccine skeptic will say is they are brand new; they were created too rapidly. When we started using dexamethasone, no one objected to the drug we’d been using for years,” Dr. Schaffner added.
But he cautioned: “These studies have come out just as new antivirals have been produced. Is the effect of SSRIs sufficiently large to compete with these antiviral drugs? Or is the actual benefit going to be so small that it is unlikely to have major clinical benefit?”
Large-scale trials needed
“Effective COVID-19 treatments […] are urgently needed to reduce COVID-19-related mortality and morbidity,” says Dr. Hoertel.
So, could SSRIs be another weapon in the armory against COVID-19?
While the findings are promising, the authors emphasize the need for “large, randomized clinical trials […] to clarify the influence of SSRIs in general, or specifically, fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.”
Dr. Schaffner echoed their caution in advocating SSRIs as a treatment: “The authors are meticulous in saying before we reach that conclusion, we need a large clinical trial or a series of clinical trials, depending on the stage of COVID-19 […] that we are trying to address.”
Successful phase 3 clinical trials, on the other hand, could “enrich the present therapeutic arsenal with an affordable, well-tolerated, and readily administered medicine in the global fight against COVID-19,” according to Dr. Hoertel.
