To Örebro University

BACKGROUND: Despite considerable interest in the consequences of benzodiazepine and benzodiazepine-related Z-drug (BZDR) use, little is known about whether and how initiation of BZDR treatment relates to the development of alcohol- and drug-related problems. AIMS: This study aimed to examine the association of incident BZDR dispensing with subsequent alcohol- and drug-related problems.

METHODS: This nationwide register-based study included demographically matched and co-twin control cohorts. Among all Swedish residents aged older than 10 years and BZDR-naïve by 2007, 960,430 BZDR-recipients with incident dispensation in 2007-2019 and without any recorded pre-existing substance-related conditions were identified and matched (1:1) to non-recipients from the general population. Twin BZDR-recipients (n = 12,048) were linked to 12,579 unexposed co-twins. Outcomes included alcohol and drug use disorders, poisoning, deaths, and related suspected criminal offences. Flexible parametric survival models estimated outcome risks across up to 14 years of follow-up.

RESULTS: In the demographically matched cohort (60% women, median age at BZDR initiation 51 years), incidence rates in BZDR-recipients and non-recipients (per 1000 person-years) were 5.60 versus 2.79 for alcohol-related and 4.15 versus 1.23 for drug-related problems, respectively. In fully adjusted models, relative risks were increased for alcohol- and drug-related problems (adjusted hazard ratio (95% confidence interval): 1.56 (1.53-1.59) and 2.11 (2.05-2.17), respectively). The risks persisted within the co-twin comparison, different follow-ups, and all additional sensitivity analyses.

CONCLUSIONS: BZDR initiation was associated with a small but robust increase in absolute and relative risks of developing alcohol- and drug-related problems. The findings contribute to evidence base for making decisions on BZDR treatment initiation.