A retrospective US study yesterday in JAMA Network Open suggests that adult COVID-19 patients taking a selective serotonin reuptake inhibitor (SSRI) antidepressant—particularly fluoxetine hydrochloride (Prozac) or fluvoxamine maleate (Luvox)—were less likely to die of their infections than those not taking the drugs.
SSRIs, which are used for treating depression and other psychological conditions, are one of the most commonly prescribed, widely available antidepressant classes.
University of California San Francisco (UCSF) and Stanford University researchers analyzed information from the Cerner Real World COVID-19 electronic health record database of 83,584 patients who tested positive for COVID-19 from January to September 2020 at 87 US medical centers.
Their outcomes were compared with those of 80,283 matched control patients not taking an SSRI. Average patient age was 63.8 years, and 59.8% were women.
Fluoxetine tied to 28% reduction in death
Relative risk (RR) of death among the 3,401 patients with a prescription for any SSRI was 8% less than among the 6,892 control patients (RR, 0.92 (14.6% vs 16.6%; RR, 0.92). Of the 470 patients taking fluoxetine, 9.8% died, relative to 13.3% of 7,050 control patients (RR, 0.72, a 28% reduction).
Ten percent of 481 patients taking fluoxetine or fluvoxamine died, versus 13.3% of 7,215 control patients (RR, 0.74, a 26% reduction). But the link between taking any SSRI other than fluoxetine or fluvoxamine and risk of death was not significant for every iteration performed (15.4% of 2,898 vs 17.0% of 8,694 controls; RR, 0.92, a reduction of 8%).
The researchers said that possible explanations for the benefit of SSRIs in COVID-19 patients include their ability (in particularly, of fluoxetine) to decrease levels of pro-inflammatory cytokines, modulate damaging aspects of the inflammatory response, and inhibit entry of SARS-CoV-2 into cells. Some studies, they said, have suggested that SSRIs, and fluoxetine in particular, have antiviral effects.
While the study could indicate that SSRIs reduce death among COVID-19 patients, unaccounted confounding factors could have influenced the results, the study authors said.
"These findings suggest that SSRIs, if proven effective, could be a therapeutic option to reduce mortality among patients with COVID-19," they wrote. "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."
In a UCSF news release, lead author Tomiko Oskotsky, MD, said the results are encouraging.
"It's important to find as many options as possible for treating any condition," she said. "A particular drug or treatment may not work or be well tolerated by everyone. Data from electronic medical records allow us to quickly look into existing drugs that could be repurposed for treating COVID-19 or other conditions."