Summary: A comparison of medical records reveals people who took SSRI antidepressants, specifically fluoxetine (Prozac), were less likely to die of COVID-19 than a matched control group. The findings add to a growing body of evidence that SSRIs may have beneficial effects against the worst symptoms of coronavirus.
A large analysis of health records from 87 health care centers across the United States found that people taking a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), particularly fluoxetine, were significantly less likely to die of COVID-19 than a matched control group.
The results add to a body of evidence indicating that SSRIs may have beneficial effects against the worst symptoms of COVID-19, although large randomized 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, PhD, associate professor of pediatrics and a member of the Bakar Computational Health Sciences Institute (BCHSI) at UC San Francisco. “There’s power in the numbers.”
The UCSF-Stanford research team analyzed electronic health records from the Cerner Real World COVID-19 de-identified database, which had information from almost 500,000 patients across the U.S. 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 showed that patients taking fluoxetine were 28 percent less likely to die; those taking either fluoxetine or another SSRI called fluvoxamine were 26 percent less likely to die; and the entire group of patients taking any kind of SSRI was 8 percent 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 Tomiko Oskotsky, MD, 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.”
Authors: Other authors include David K. Stevenson, MD, Ivana Marić, PhD, Ronald J. Wong, PhD, and Nima Aghaeepour, PhD, of Stanford University; and Alice Tang and Boris Oskotsky, PhD, of UCSF.
Dr. Sirota reported serving as a scientific advisor at Aria Pharmaceuticals, Inc. No other disclosures were reported.
Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants
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.
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.
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.
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.
About this COVID-19 research news
Original Research: Open access.
“Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants” by Marina Sirota et al. JAMA Network Open