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

• Published in: Epidemiology and psychiatric sciences 2022-03, Vol.31, p.e18, Article e18
• Main Authors: Hoertel, N., Sánchez-Rico, M., Gulbins, E., Kornhuber, J., Vernet, R., Beeker, N., Neuraz, A., Blanco, C., Olfson, M., Airagnes, G., Lemogne, C., Alvarado, J. M., Arnaout, M., Cougoule, C., Meneton, P., Limosin, F.
• Format: Article
• Language: English
• Subjects: Benzodiazepines; Coronaviruses; COVID-19; COVID-19 - mortality; Drug administration; GABA-A Receptor Antagonists - adverse effects; Hospitalization; Human health and pathology; Humans; Life Sciences; Mortality; Observational studies; Original; Original Article; Proportional Hazards Models; Psychiatry
• ISSN: 2045-7960; 2045-7979
• DOI: 10.1017/S2045796021000743

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