Do the Selective Serotonin Reuptake Inhibitor Antidepressants Fluoxetine and Fluvoxamine Reduce Mortality Among Patients With COVID-19?

In a large, multicenter, retrospective cohort study of 83 584 patients with laboratory-confirmed COVID-19 who had an emergency department or urgent care visit or were admitted for observation or hospitalized across 87 health care centers in the US, Oskotsky et al 1 observed an association between selective serotonin reuptake inhibitor (SSRI) administration and reduced mortality in 3401 patients with COVID-19 compared with 6802 matched control patients who were not given SSRIs but shared similar sociodemographic characteristics, medical comorbidities, and medication indication.Interestingly, among SSRIs, a significant association between treatment and reduced mortality was observed for fluoxetine and for fluoxetine or fluvoxamine.These results confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19.2,3 First, a prior multicenter, retrospective, observational study involving patients who were hospitalized for COVID-19 in Paris, France, indicated that antidepressant use-particularly fluoxetine use-was associated with reduced risk of intubation or death. 2 Second, several preclinical studies support a substantial in vitro efficacy of different SSRI-and non-SSRI antidepressants-particularly fluoxetine-against SARS-CoV-2 with different host cells (eg, Vero E6, Calu-1, Calu-3, HEK293T-ACE2-+