Key Points Question Are selective serotonin reuptake inhibitors (SSRIs), specifically fluoxetine hydrochloride, associated with a lower mortality risk among patients with COVID-19? Findings In this multicenter cohort study analyzing electronic health records of 83 584 patients diagnosed with COVID-19, including 3401 patients who were prescribed SSRIs, a reduced relative risk of mortality was found to be associated with the use of SSRIs—specifically fluoxetine—compared with patients who were not prescribed SSRIs. Meaning These findings suggest that SSRI use may reduce mortality among patients with COVID-19, although they may be subject to unaccounted confounding variables; further investigation via large, randomized clinical trials is needed. This cohort study investigates whether use of selective serotonin reuptake inhibitors is associated with a reduction in the relative risk of mortality for patients with COVID-19. Importance Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)—specifically fluoxetine hydrochloride and fluvoxamine maleate—with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size. Objective To investigate the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs). Design, Setting, and Participants This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse 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 centers across the US. Exposures Selective serotonin reuptake inhibitors and specifically (1) fluoxetine, (2) fluoxetine or fluvoxamine, and (3) other SSRIs (ie, not fluoxetine or fluvoxamine). Main Outcomes and Measures Death. Results A total of 3401 adult patients with COVID-19 prescribed SSRIs (2033 women [59.8%]; mean [SD] age, 63.8 [18.1] years) were identified, with 470 receiving fluoxetine only (280 women [59.6%]; mean [SD] age, 58.5 [18.1] years), 481 receiving fluoxetine or fluvoxamine (285 women [59.3%]; mean [SD] age, 58.7 [18.0] years), and 2898 receiving other SSRIs (1733 women [59.8%]; mean [SD] age, 64.7 [18.0] years) within a defined time frame. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06). Conclusions and Relevance These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and 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.
【초록키워드】 randomized clinical trial, Mortality, severe COVID-19, Comorbidities, risk, outcome, database, Electronic health record, cohort study, outcomes, Health, severity of COVID-19, Research, Patient, age, women, medication, Care, association, Evidence, propensity score matching, exposure, antidepressant, EHR, demographic characteristics, Support, risk of death, retrospective cohort study, Proinflammatory cytokine, Frame, decreased mortality, subject, control patients, measure, participant, finding, selective, objective, setting, multicenter cohort study, reduce mortality, lower mortality risk, Result, defined, involved, reported, receiving, reduced, treated, adjusted, reflected, suggested, representing, reduction in, statistically significant, Importance, was reduced, control patient, diagnosed with COVID-19, duration of follow-up, patients with COVID-19, Point, Relevance, RR of mortality, serotonin reuptake inhibitor, 【제목키워드】 COVID-19, antidepressant, Reuptake,