Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study.

Affiliation

Hoertel N(1)(2)(3), Sánchez-Rico M(4)(5), Vernet R(6), Beeker N(7), Jannot AS(8)(6)(9), Neuraz A(9)(10), Salamanca E(11), Paris N(12)(13), Daniel C(12)(14), Gramfort A(15), Lemaitre G(15), Bernaux M(16), Bellamine A(7), Lemogne C(4)(17)(8), Airagnes G(4)(17)(8), Burgun A(9), Limosin F(4)(17)(8); AP-HP / Universities / INSERM COVID-19 Research Collaboration and AP-HP COVID CDR Initiative.
Author information:
(1)AP-HP.Centre-Université de Paris, Hôpital Corentin-Celton, Département Médico-Universitaire de Psychiatrie et Addictologie, 92130, Issy-les-Moulineaux, France. [Email]
(2)INSERM, Institut de Psychiatrie et Neurosciences de Paris, UMR_S1266, Paris, France. [Email]
(3)Université de Paris, Faculté de Santé, UFR de Médecine, Paris, France. [Email]
(4)AP-HP.Centre-Université de Paris, Hôpital Corentin-Celton, Département Médico-Universitaire de Psychiatrie et Addictologie, 92130, Issy-les-Moulineaux, France.
(5)Department of Psychobiology & Behavioural Sciences Methods, Faculty of Psychology, Universidad Complutense de Madrid, Campus de Somosaguas, Pozuelo de Alarcon, Spain.
(6)AP-HP.Centre-Université de Paris, Hôpital Européen Georges Pompidou, Medical Informatics, Biostatistics and Public Health Department, F-75015, Paris, France.
(7)AP-HP.Centre-Université de Paris, Unité de Recherche clinique, Hôpital Cochin, Paris, France.
(8)Université de Paris, Faculté de Santé, UFR de Médecine, Paris, France.
(9)INSERM, UMR_S1138, Cordeliers Research Center, Université de Paris, Paris, France.
(10)AP-HP.Centre-Université de Paris, Necker-Enfants Malades Hospital, Department of Medical Informatics, 75015, Paris, France.
(11)Banque Nationale de Données Maladies Rares, Campus Picpus, Département WIND
(Web Innovation Données), Paris, France.
(12)AP-HP, DSI-WIND
(Web Innovation Données), Paris, France.
(13)LIMSI, CNRS, Université Paris-Sud and Université Paris-Saclay, F-91405, Orsay, France.
(14)Sorbonne University, University Paris 13, Sorbonne Paris Cité, INSERM UMR_S1142, F-75012, Paris, France.
(15)Université Paris-Saclay, INRIA, CEA, Palaiseau, France.
(16)Direction de la stratégie et de la transformation, AP-HP, Paris, France.
(17)INSERM, Institut de Psychiatrie et Neurosciences de Paris, UMR_S1266, Paris, France.

Abstract

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.