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Observational Study
. 2022 Mar 30:31:e18.
doi: 10.1017/S2045796021000743.

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

N Hoertel  1   2   3 , M Sánchez-Rico  1   4 , E Gulbins  5 , J Kornhuber  6 , R Vernet  7 , N Beeker  8 , A Neuraz  9   10 , C Blanco  11 , M Olfson  12 , G Airagnes  1   2   3   13 , C Lemogne  2   3   14 , J M Alvarado  4 , M Arnaout  15 , C Cougoule  16 , P Meneton  17 , F Limosin  1   2   3 ; AP-HP/Université de Paris/INSERM COVID-19 Research Collaboration/AP-HP COVID CDR Initiative/‘Entrepôt de Données de Santé’ AP-HP Consortium
Affiliations
Observational Study

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

N Hoertel et al. Epidemiol Psychiatr Sci. .

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.

Keywords: Benzodiazepine; COVID-19; SARS-CoV-2; mortality.

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Conflict of interest statement

NH, MS-R, MA, EG, JK, AC and FL are inventors of a patent application related to methods of treating COVID-19, filled by Assistance Publique – Hôpitaux de Paris in France. Other authors declare no conflict of interest related to this work.

Figures

Fig. 1.
Fig. 1.
Kaplan–Meier curves for mortality in the full sample crude analysis (N = 14 381) (A), in the full sample analysis with IPW (N = 14 381) (B), and in the matched analytic sample using a 1 : 1 ratio (N = 1372) (C), according to BZRA use at baseline, among adult patients hospitalised for COVID-19. The shaded areas represent pointwise 95% CIs. Numbers at risk in panel B are weighted.
See this image and copyright information in PMC

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