Research: less risk of dying from covid-19 linked with antidepressants

Antidepressant use is related with a lower risk of death in individuals with COVID-19 infections, according to recent study. The findings, derived from a survey of over 80,000 individuals infected with COVID-19 in the United States last year, show that persons taking selective serotonin reuptake inhibitors (SSRIs) had a much greater likelihood of surviving than comparable patients who did not use the meds.

“Our subgroup analysis found a statistically significant reduction in the relative risk of mortality of 28% for patients treated with fluoxetine and 26% for patients treated with fluoxetine or fluvoxamine,” researchers explain in the new study, which was co-authored by researchers from the University of California, San Francisco (UCSF) and Stanford University.

While the findings reveal simply a connection in the data – not confirmation of a causal influence – this isn’t the first time this association has been discovered.

A number of studies have observed that antidepressant use is somehow associated with better outcomes for COVID-19 patients, although the precise mechanisms behind the phenomenon are not yet fully understood.

Nonetheless, scientists are making progress with each new analysis, and have plenty of ideas as to why SSRIs might be able help to protect people from succumbing to severe or deadly cases of COVID-19 – and it’s likely to be more than just one channel that’s involved.

“It has been previously observed that SSRIs may have anti-inflammatory properties mediated through a reduction of several proinflammatory cytokines, including interleukin 6 and tumor necrosis factor,” the team, led by first author and computational health scientist Tomiko Oskotsky from UCSF, writes in the new study.

Beyond anti-inflammatory effects, it’s also possible that SSRIs might be working against processes that help the coronavirus to take hold in the body.

SSRI antidepressants, including fluoxetine and fluvoxamine, belong to the group of pharmacological compounds called functional inhibitors of acid sphingomyelinase (FIASMA).

These compounds inhibit an enzyme called acid sphingomyelinase (ASM), which breaks down sphingomyelin, a lipid in cell membranes, into other molecules, including one called ceramide.

“Preclinical data indicate that SARS-CoV-2 activates the ASM-ceramide system, resulting in the formation of ceramide-enriched membrane domains that facilitate viral entry and infection by clustering ACE2, the cellular receptor of SARS-CoV-2, and the release of proinflammatory cytokines,” psychiatrist Nicolas Hoertel from the University of Paris, who wasn’t involved with the study, explains in a perspective article on the new research.

In other words, it’s possible that SSRIs, amongst other things, are making it harder for SARS-CoV-2 to infect cells, by disrupting the molecules the virus uses as anchor points.

“Importantly, the reconstitution of ceramides in cells treated with these antidepressants restores the infection,” Hoertel writes.

“Taken together, these results show the potentially crucial importance of the ASM-ceramide system as a treatment target in COVID-19.”