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

Hoertel N, Sanchez-Rico M, Gulbins E, Kornhuber J, Vernet R, Beeker N, Neuraz A, Blanco C, Olfson M, Airagnes G, Lemogne C, Alvarado JM, Arnaout M, Cougoule C, Meneton P, Limosin F (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Epidemiology and Psychiatric Sciences Cambridge University Press

Book Volume: 31

Pages Range: e18-

DOI: 10.1017/S2045796021000743

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.

Authors with CRIS profile

Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Hôpital Corentin-Celton, Hospital Corentin-Celton, APHP FR France (FR) Universität Duisburg-Essen (UDE) DE Germany (DE) Georges Pompidou European Hospital / Hôpital Européen Georges-Pompidou (HEGP) FR France (FR) University of Paris 4 - Paris-Sorbonne / Université paris IV Paris-Sorbonne FR France (FR) National Institute on Drug Abuse (NIDA) US United States (USA) (US) Columbia University US United States (USA) (US) Hôpitaux Universitaires Paris-Ouest FR France (FR) Université Fédérale de Toulouse Midi-Pyrénées FR France (FR) University of Paris 6 - Pierre et Marie Curie / Université Paris VI Pierre et Marie Curie (UPMC) FR France (FR) Hôpital Cochin FR France (FR) Universidad Complutense de Madrid (UCM) ES Spain (ES)

How to cite

APA:

Hoertel, N., Sanchez-Rico, M., Gulbins, E., Kornhuber, J., Vernet, R., Beeker, N.,... Limosin, F. (2022). Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study. Epidemiology and Psychiatric Sciences, 31, e18-. https://doi.org/10.1017/S2045796021000743

MLA:

Hoertel, Nicolas, et al. "Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study." Epidemiology and Psychiatric Sciences 31 (2022): e18-.

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