Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study
Nicolas Hoertel, Marina Sánchez-Rico, Raphaël Vernet, Nathanaël Beeker, Anne-Sophie Sophie Jannot, Antoine Neuraz, Elisa Salamanca, Nicolas Paris, Christel Daniel, Alexandre Gramfort, Guillaume Lemaitre, Mélodie Bernaux, Ali Bellamine, Cédric Lemogne, Guillaume Airagnes, Anita Burgun, Frédéric Limosin
Molecular Psychiatry, doi:10.1038/s41380-021-01021-4
A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43-0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.
Conflict of interest All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organization for the submitted work; NH has received personal fees and non-financial support from Lundbeck, outside the submitted work. FL has received speaker and consulting fees from Janssen-Cilag, Euthérapie-Servier, and Lundbeck, outside the submitted work. CL reports personal fees and non-financial support from Janssen-Cilag, Lundbeck, Otsuka Pharmaceutical, and Boehringer Ingelheim, outside the submitted work. GA reports personal fees from Pfizer, Pierre Fabre and Lundbeck, outside the submitted work; other authors declare no financial relationships with any organization that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval This observational study using routinely collected data received approval from the Institutional Review Board of the AP-HP clinical data warehouse (decision CSE-20-20_COVID19, IRB00011591, April 8th, 2020). AP-HP clinical Data Warehouse initiative ensures patients' information and informed consent regarding the different approved studies through a transparency portal in accordance with European Regulation on data protection and authorization n°1980120 from National Commission for Information Technology and Civil Liberties (CNIL). All procedures..
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