Incident benzodiazepine and Z-drug use and subsequent risk of alcohol- and drug-related problems : A nationwide matched cohort study with co-twin comparison
(2025) In Journal of Psychopharmacology- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- alcohol use disorders, benzodiazepines, drug use disorders, Z-drugs
- in
- Journal of Psychopharmacology
- publisher
- SAGE Publications
- external identifiers
-
- pmid:41035208
- scopus:105017872824
- ISSN
- 0269-8811
- DOI
- 10.1177/02698811251373069
- language
- English
- LU publication?
- yes
- id
- 3bda3b36-b255-4eee-b757-f0cfe9bb1360
- date added to LUP
- 2025-12-05 12:06:02
- date last changed
- 2025-12-19 14:01:58
@article{3bda3b36-b255-4eee-b757-f0cfe9bb1360,
abstract = {{<p>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.</p>}},
author = {{Wang, Xinchen and Chang, Zheng and Molero, Yasmina and Isomura, Kayoko and Fernández de la Cruz, Lorena and Lichtenstein, Paul and Kuja-Halkola, Ralf and D’Onofrio, Brian M. and Quinn, Patrick D. and Larsson, Henrik and Brikell, Isabell and Hellner, Clara and Hasselström, Jan and Jayaram-Lindström, Nitya and Mataix-Cols, David and Sidorchuk, Anna}},
issn = {{0269-8811}},
keywords = {{alcohol use disorders; benzodiazepines; drug use disorders; Z-drugs}},
language = {{eng}},
publisher = {{SAGE Publications}},
series = {{Journal of Psychopharmacology}},
title = {{Incident benzodiazepine and Z-drug use and subsequent risk of alcohol- and drug-related problems : A nationwide matched cohort study with co-twin comparison}},
url = {{http://dx.doi.org/10.1177/02698811251373069}},
doi = {{10.1177/02698811251373069}},
year = {{2025}},
}