Findings from a study published in JAMA Network Open support evidence that selective serotonin reuptake inhibitors (SSRIs) may be associated with reduced severity of coronavirus disease 2019 (COVID-19) reflected in the reduced relative risk (RR) of mortality.
“We observed a small, statistically significant reduction of 8% in the RR of mortality among patients with COVID-19 prescribed SSRIs when compared with matched control patients. Our subgroup analysis found a statistically significant reduction of 28% in the RR of mortality for the patients treated with fluoxetine and 26% for the patients treated with fluoxetine or fluvoxamine,” reported Tomiko Oskotsky, MD, University of California, San Francisco, California, and colleagues.
For the study, researchers analysed data from a large electronic health record database representing a population of 83,584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centres across the US. Patients with COVID-19 and a medication order for an SSRI with an order status of active or completed and without a designation of as needed (ie, medication taken only when needed) at least once within a period of 10 days before and 7 days after their first recorded COVID-19 diagnosis were compared with matched control patients with COVID-19 and no SSRI orders.
A total of 3,401 adult patients with COVID-19 prescribed SSRIs (mean age, 63.8 years; 59.8% were women) were identified, with 470 receiving fluoxetine only, 481 receiving fluoxetine or fluvoxamine, and 2,898 receiving other SSRIs within a defined time frame. The remaining 80,183 patients who had no history of SSRI exposure were included as control patients.
When compared with matched untreated control patients, RR of mortality was reduced among patients prescribed any SSRI (14.6% [497/3,401] vs 16.6% [1,130/6,802]; RR, 0.92 [95% confidence interval (CI), 0.85-0.99]; adjusted P = 0.03); fluoxetine (9.8% [46/470] vs 13.3% [937 of 7,050]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = 0.03); and fluoxetine or fluvoxamine (10.0% [48/481] vs 13.3% [956/7,215]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = 0.04).
However, the association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (15.4% [447/2,898] vs 17.0% [1,474/8,694]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = 0.06).
“These findings suggest that SSRI use may reduce mortality among patients with COVID-19, although they may be subject to unaccounted confounding variables,” the authors noted, adding that “further research and randomised 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.”