Incident benzodiazepine and Z-drug use and subsequent risk of alcohol- and drug-related problems: a nationwide matched cohort study with co-twin comparison

BackgroundDespite 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 contributes to the development of alcohol- and drug-related problems. AimTo examine the association of incident BZDR dispensing with subsequent development of broadly defined alcohol- and drug-related problems. MethodsThis nationwide register-based study included demographically matched and co-twin control cohorts. Among all Swedish residents aged [≥]10 years and BZDR-naive 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 nonrecipients 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. ResultsIn the demographically matched cohort (60% women, median age at BZDR initiation 51 years), incidence rates in BZDR-recipients and nonrecipients (per 1000 person-years) were 5.60 vs 2.79 for alcohol-related and 4.15 vs 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 and sensitivity analyses. ConclusionsBZDR 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.