A large analysis of health records from 87 healthcare centres across the United States found that people taking selective serotonin reuptake inhibitor (SSRI) depressants, particularly fluoxetine, were significantly less likely to die of COVID-19 than a matched control group.
Electronic health records compared outcomes for patients across the country, and the results add to a body of evidence indicating that SSRIs may have beneficial effects against the worst symptoms of COVID-19, although large randomised clinical trials are needed to prove this.
“We can’t tell if the drugs are causing these effects, but the statistical analysis is showing significant association,” said Marina Sirota, associate professor of paediatrics and a member of the Bakar Computational Health Sciences Institute (BCHSI) at the University of California San Francisco. “There’s power in the numbers.”
The UCSF-Stanford research team analysed electronic health records from the Cerner Real World COVID-19 de-identified database, which had information from almost 500,000 patients across the US. This included 83,584 adult patients diagnosed with COVID-19 between January and September 2020. Of those, 3,401 patients were prescribed SSRIs.
The large size of the dataset enabled researchers to compare the outcomes of patients with COVID-19 on SSRIs to a matched set of patients with COVID-19 who were not taking them, thus teasing out the effects of age, sex, race, ethnicity, and comorbidities associated with severe COVID-19, such as diabetes and heart disease, as well as the other medications the patients were taking.
The results, published in JAMA Network Open, showed that patients taking fluoxetine were 28% less likely to die; those taking either fluoxetine or another SSRI called fluvoxamine were 26% less likely to die; and the entire group of patients taking any kind of SSRI was 8% less likely to die than the matched patient controls.
Though the effects are smaller than those found in recent clinical trials of new antivirals developed by Pfizer and Merck, the researchers said more treatment options are still needed to help bring the pandemic to an end.
“The results are encouraging,” said Dr Tomiko Oskotsky, a research scientist in Sirota’s lab at BCHSI. “It’s important to find as many options as possible for treating any condition. 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.”
Study details
Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants
Tomiko Oskotsky, Ivana Marić, Alice Tang, Boris Oskotsky, Ronald J. Wong, Nima Aghaeepour, Marina Sirota, David K. Stevenson.
Published in JAMA Network Open on 15 November 2021
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 multicentre cohort study analysing 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.
Abstract
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 analysing 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 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.
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