Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants
Retrospective database analysis of 83,584 patients in the USA, showing lower mortality with existing fluoxetine use in PSM analysis. There were 11 fluvoxamine patients, showing non-statistically significant higher mortality.
risk of death, 57.9% higher, RR 1.58, p = 0.62, treatment 2 of 11 (18.2%), control 19 of 165 (11.5%), fluvoxamine.
risk of death, 26.0% lower, RR 0.74, p = 0.04, treatment 48 of 481 (10.0%), control 956 of 7,215 (13.3%), NNT 31, fluoxetine.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Oskotsky et al., 15 Nov 2021, retrospective, propensity score matching, USA, peer-reviewed, 8 authors.
Abstract: Original Investigation | Infectious Diseases
Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin
Reuptake Inhibitor Antidepressants
Tomiko Oskotsky, MD; Ivana Marić, PhD; Alice Tang, BS; Boris Oskotsky, PhD; Ronald J. Wong, PhD; Nima Aghaeepour, PhD; Marina Sirota, PhD; David K. Stevenson, MD
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.
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
OBJECTIVE To investigate the association of SSRIs with outcomes in patients with COVID-19 by
study analyzing electronic health
analyzing electronic health records (EHRs).
records of 83 584 patients diagnosed
with COVID-19, including 3401 patients
DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used propensity score
who were prescribed SSRIs, a reduced
matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-
relative risk of mortality was found to be
treated patients with matched control patients not treated with SSRIs within a large EHR database
associated with the use of SSRIs—
representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to
specifically fluoxetine—compared with
September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers
patients who were not prescribed SSRIs.
across the US.
Meaning These findings suggest that
SSRI use may reduce mortality among
EXPOSURES Selective serotonin reuptake inhibitors and specifically (1) fluoxetine, (2) fluoxetine or
fluvoxamine, and (3) other SSRIs (ie, not fluoxetine or fluvoxamine).
patients with COVID-19, although they
may be subject to unaccounted
confounding variables; further
MAIN OUTCOMES AND MEASURES Death.
investigation via large, randomized
clinical trials is needed.
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
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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..
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