Common antidepressant reduces risk of death by 26%

  • A growing body of evidence indicates that a common antidepressant can reduce symptom severity and mortality following infection with SARS-CoV-2.
  • In an observational study, patients taking selective serotonin reuptake inhibitors (SSRIs) were 8% less likely to die from COVID-19.
  • Those who took fluoxetine or fluvoxamine were 26% less likely to die.
  • Phase 3 clinical trials are needed to see if researchers can replicate these observations on a large scale.

In the hunt for COVID-19 treatments, several drugs have shown promise. Currently, the two oral antivirals, Molnupiravir, from Merck, and Paxlovid, from Pfizer, are hailed by many as the response to the pandemic. However, there is still some questions on their efficacy and safety, so that the search for safe and effective treatments continues.

Now, an observational study has shown that some of the more common prescription antidepressants can reduce both the severity of COVID-19 and mortality from the disease.

Researchers at the University of California and Stanford University School of Medicine conducted a retrospective cohort study of 83,584 people diagnosed with COVID-19. They found that people who took SSRIs had a lower relative risk of death than those who did not.

In the USA, 13.2% of adults (17.7% of women) take SSRIs. The group of drugs includes:

This study adds to evidence from previous research on the effects of SSRIs. Three clinical trials, only one published last month, found that the use of fluvoxamine was linked to a reduced risk of clinical deterioration after infection with SARS-CoV-2.

Dr. William Schaffner, professor of infectious diseases at Vanderbilt University Medical Center, Nashville, TN, commented on the study: “I would say it’s very provocative. This is a large ecological study that builds on previous information suggesting that this class [of drugs] may in fact have a role in the treatment [SARS-CoV-2] infections. “

Of those interviewed in the study, which appears in JAMA network open, 3,401 were taking SSRIs. Researchers matched participants for socio-demographic characteristics, medical comorbidities, and medication indication with 6,802 controls who were not taking SSRIs.

The SSRI group had a relative reduction (RR) in mortality of 8% compared to the control group. The decrease was greatest in people taking fluoxetine (RR 28%) and those taking fluvoxamine or fluoxetine (26%). Other SSRIs have not shown such a strong effect.

“These results confirm and extend previous findings from observational, preclinical and clinical studies suggesting that certain SSRI antidepressants […] could be beneficial against COVID-19. “

Dr Nicolas Hoertel, MD, M.PH., Ph.D., writes in an accompanying editorial.

One of the advantages of SSRIs over newer treatments, such as the antivirals scientists are developing, is that they have been widely used for many years and their side effects are well known.

“Familiarity, a certain level of comfort, is a big advantage. Even though vaccines have been used in millions of people, one of the first things a vaccine skeptic will say is that they are brand new; they were created too quickly. When we first started using dexamethasone, no one objected to the drug that we had been using for years, ”said Dr Schaffner.

But he cautioned, “These studies came out as new antivirals were being produced. Is the effect of SSRIs large enough to compete with these antiviral drugs? Or is the actual benefit going to be so low that it is unlikely to have a major clinical benefit?

Dr Hoertel Says: “Effective Treatments for COVID-19 […] are urgently needed to reduce COVID-19 mortality and morbidity. ”

So could SSRIs be another weapon in the arsenal against COVID-19?

Although these results are encouraging, the authors stress the need for “large randomized clinical trials […] to clarify the effect of SSRIs in general, or more specifically, fluoxetine and fluvoxamine, on the severity of COVID-19 findings. “

Dr Schaffner echoed their caution in advocating SSRIs as a treatment: “The authors are meticulous in saying before we come to this conclusion, we need a large clinical trial or a series of clinical trials, by stage of COVID-19 […] that we are trying to resolve.

However, Dr Hoertel says successful Phase 3 clinical trials could “enrich the current therapeutic arsenal with an inexpensive, well-tolerated and easily administered drug in the global fight against COVID-19.”


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