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Journal Article Multicenter Study Observational Study Epublish 11 citations

PubMed: 35352674 DOI: 10.1017/S2045796021000743

Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

Epidemiol Psychiatr Sci 31:e18

Authors: N Hoertel, M Sánchez-Rico, E Gulbins, J Kornhuber, R Vernet, N Beeker, A Neuraz, C Blanco, M Olfson, G Airagnes, C Lemogne, J M Alvarado, M Arnaout, C Cougoule, P Meneton, F Limosin

Affiliations

  • Département de Psychiatrie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Corentin-Celton, DMU Psychiatrie et Addictologie, Issy-les-Moulineaux, France.
  • Université de Paris, Paris, France.
  • INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, Paris, France.
  • Department of Psychobiology & Behavioural Sciences Methods, Faculty of Psychology, Universidad Complutense de Madrid, Campus de Somosaguas, Pozuelo de Alarcon, Spain.
  • Institute for Molecular Biology, University Medicine Essen, University of Duisburg-Essen, Essen, Germany.
  • Department of Psychiatry and Psychotherapy, University Hospital Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.
  • Medical Informatics, Biostatistics and Public Health Department, AP-HP, Centre-Université de Paris, Hôpital Européen Georges Pompidou, F-75015Paris, France.
  • Assistance Publique-Hôpitaux de Paris (AP-HP), Unité de Recherche Clinique, Hôpital Cochin, Paris, France.
  • INSERM, UMR_S 1138, Cordeliers Research Center, Université de Paris, Paris, France.
  • Department of Medical Informatics, AP-HP, Centre-Université de Paris, Necker-Enfants Malades Hospital, Paris, France.
  • Division of Epidemiology, Services and Prevention Research, National Institute on Drug Abuse, 6001 Executive Boulevard, Bethesda, MD20852, USA.
  • Department of Psychiatry, Columbia University/New York State Psychiatric Institute, 1051 Riverside Drive, Unit 69, New York, NY10032, USA.
  • INSERM, UMS 011, Population-based Epidemiologic Cohorts, Villejuif, France.
  • AP-HP, Hôpital Hôtel-Dieu, DMU Psychiatrie et Addictologie, Service de Psychiatrie de l'adulte, Paris, France.
  • Anesthesia and Intensive Care Department, Hôpitaux Universitaires Paris Île-de-France Ouest, Boulogne-Billancourt, France.
  • Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, Toulouse, France.
  • INSERM U1142 LIMICS, UMRS 1142, Sorbonne Universities, UPMC University of Paris 06, University of Paris 13, Paris, France.

Abstract

AIMS

To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19).

METHODS

A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW).

RESULTS

Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment.

CONCLUSIONS

BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.

MeSH

Mortality, Epidemiology, Diazepam, Covid-19, Sars-Cov-2

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