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Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.
A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.
“We can’t tell if the drugs are causing these effects, but the statistical analysis is showing significant association. There’s power in the numbers,” Marina Sirota, PhD, University of California San Francisco (UCSF), said in a statement.
The study was published online November 15 in JAMA Network Open.
Data-Driven Approach
Investigators analyzed data from the Cerner Real World Data COVID-19 de-identified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3401 patients who were prescribed SSRIs.
When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk [RR], 0.72; 95% CI, 0.54 – 0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55 – 0.99; adjusted P = .04) versus those not on these medications.
Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85 – 0.99; adjusted P = .03).
“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Sirota told Medscape Medical News.
“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.
“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told Medscape Medical News.
Urgent Need
The current 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,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital in France, writes in a linked editorial.
Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.
“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 — especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries — are urgently needed to reduce COVID-19-related mortality and morbidity,” Hoertel points out.
“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.
The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.
JAMA Netw Open. Published November 15, 2021. Article, Editorial
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