Do Antidepressants Reduce Mortality in COVID-19?

Fluoxetine and fluvoxamine reduced the relative risk (RR) of mortality in COVID-19 in a study recently published in JAMA Network Open.

The objective of the current study was to add to the body of research exploring whether antidepressants might reduce mortality in COVID-19. Previous studies have indicated selective serotonin reuptake inhibitors (SSRIs) reduce proinflammatory cytokines and inhibit the acid sphingomyelinase/ceramide system, which could impact a SARS-CoV-2 infection.

Data were drawn from the Cerner Real World Data COVID-19 database and utilized the information from adult patients (n=83,584) with confirmed COVID-19 across 87 health care centers. The patients visited the emergency department or urgent care, became hospitalized, or were admitted for observation. The researchers compared patients who were actively taking SSRIs (had an order status of active or completed at least once within 10 days before and 7 days after their first recorded COVID-19 diagnosis) with a control group of patients with COVID-19 who did not have SSRI orders.

The patients (n=3401 59.8% women, mean 63.8 years old) taking SSRIs received fluoxetine (n=470), fluvoxamine (n=11), fluoxetine or fluvoxamine (n=481), or any of the following (n=2898): escitalopram oxalate, paroxetine hydrochloride, paroxetine mesylate, sertraline hydrochloride, fluoxetine, citalopram hydrobromide, vortioxetine hydrobromide, fluvoxamine or vilazodone hydrochloride.

The mortality rate of patients taking SSRIs (14.6%) was lower compared with the matched control individual (range 16.3% to 16.6%), with an 8% reduction in RR (0.92 adjusted P =.03). Patients taking fluoxetine had a 28% reduction in RR compared with control individuals (9.8% vs. 13.3%-13.4% adjusted P =.03). Fluoxetine- or fluvoxamine-treated patients (10.0% mortality rate) had an RR of 26% (adjusted P =.04) compared with control individuals (13.3%-13.4%). The association between receiving SSRIs that are not fluoxetine or fluvoxamine and mortality was not significant.

Among patients who received any SSRI, mean fluoxetine-equivalent dose was 30.2 mg/d for the 88.4% of patients who had dose information available. Mean fluoxetine dose was 28.2 mg/d (86.0% data availability). Mean fluoxetine-equivalent dose was 29.0 mg/d for patients taking fluoxetine or fluvoxamine. Patients who received SSRIs other than fluvoxamine had a mean equivalent dose of 30.4 mg/d (88.3% data availability).

One of the imitations of the study was that the retrospective nature of the study only allowed researchers to identify an association between SSRI treatment and COVID-19 mortality, but not causal effects.

“These findings suggest that SSRIs, if proven effective, could be a therapeutic option to reduce mortality among patients with COVID-19,” the researchers said.

“Further research and large, randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.