Patterns of Benzodiazepine Use and Excess Risk of All-Cause Mortality in the Elderly: A Nationwide Cohort Study

Introduction Despite the risks associated with their use, benzodiazepines remain used more widely than wisely. In this context, a better understanding of how their patterns of use can be associated with an increased risk of death appears essential. Indeed, the studies that investigated this association so far are inconsistent and question the influence of potential biases. Objective The objective of this study was to investigate the association of various patterns of benzodiazepine use with all-cause mortality. Methods A nationwide cohort of non-prevalent benzodiazepine users aged >= 65 years was identified using French healthcare insurance system claims databases. Exposure to benzodiazepines considered short-term, chronic (defined as a cumulated >= 6-month period over the previous 12 months), ongoing, and discontinued use. Using a Cox model, adjusted hazard ratios for all-cause mortality were estimated according to benzodiazepine patterns of use; exposure and confounders were treated as time-dependent variables. Results In the cohort of 54,958 individuals aged >= 65 years, adjusted hazard ratios for all-cause mortality and benzodiazepines were 2.26 (95% confidence interval 1.96-2.61) for short-term use, 3.86 (3.04-4.90) for chronic use-discontinued, and 3.05 (2.17-4.29) for chronic use-ongoing. At age 80 years, these were 1.62 (1.48-1.79), 2.00 (1.82-2.19) and 1.13 (1.02-1.26), respectively. Adjusted hazard ratios show similar decreases with age for all patterns of benzodiazepine use. Conclusions These findings confirm the existence of an excess risk of mortality associated with benzodiazepine use and provide pattern- and age-specific estimates. Higher risks were observed for patients aged < 80 years, short-term use, or chronic use recently interrupted. If the two latter can relate to an indication bias, the associations found for ongoing chronic use and short-term use conversely support a potential causal hypothesis.