Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 2;26(1):2.
doi: 10.1186/s13063-024-08692-8.

Benzodiazepine agonist treatment for patients with benzodiazepine dependence undergoing opioid agonist treatment: a study protocol for the randomized controlled trial BMX-BAR

Fatemeh Chalabianloo  1   2 , Lars Thore Fadnes  3   4 , Jörg Assmus  5 , Jon Mordal  3   6 , Kristin K Solli  6   7   8 , Kjetil S Dale  9 , Christina D Andersen  3 , Silvia Zavenova  3 , Beathe H Rønning  3 , Andreas W Blomkvist  10   11 , Martin Ryssdal  10 , Wasifa S J Butt  12 , Anne Marciuch  12 , Anne G Ørmen  13 , Christian Ohldieck  3 , Else-Marie Løberg  14   15 , Kjell Arne Johansson  3   4 ; BMX-BAR and NORCATS study group
Collaborators, Affiliations

Benzodiazepine agonist treatment for patients with benzodiazepine dependence undergoing opioid agonist treatment: a study protocol for the randomized controlled trial BMX-BAR

Fatemeh Chalabianloo et al. Trials. .

Abstract

Background: There is a lack of knowledge on effective treatment methods for comorbid benzodiazepine dependence in populations undergoing opioid agonist treatment (OAT). Tapering and discontinuation of benzodiazepines has long been considered the standard treatment, even though there is limited evidence for this practice. There is also limited research on benzodiazepine agonist treatment; however, peer and clinical experiences indicate that such approaches may be beneficial for a subgroup of the patients with long-lasting benzodiazepine dependence not responding to other treatment approaches. A randomized controlled trial will be conducted to compare the efficacy and safety of stabilizing agonist treatment using prescribed benzodiazepines with standard treatment in reducing illicit benzodiazepine use.

Methods: The target sample is 108 participants at outpatient OAT clinics in six Norwegian cities/counties (Bergen/Vestland, Tønsberg/Vestfold, Skien/Telemark, Fredrikstad/Østfold, Tromsø/Troms, and Lillestrøm/Akershus). The main inclusion criteria are benzodiazepine dependence of ≥ 5 years, using ≥ 5 days a week during the last month, and previous attempts at tapering. Participants will be randomly assigned to receive either a 26-week benzodiazepine stabilizing treatment (15-30 mg diazepam or 50-100 mg oxazepam daily), or a 20-week tapering using the same medications and equivalent initial dosages. All participants will be given access to consultations from OAT therapists with psychosocial follow-up in accordance with current clinical practice. The primary outcome is the use of illicit benzodiazepines assessed by observed urinary tests at week 24. Secondary outcomes include mental health symptoms, quality of life, cognitive performance, violence risk, other substance use, treatment retention, and life satisfaction. Additionally, the study will assess treatment-related adverse events as well as the cost-effectiveness of the intervention.

Discussion: This is the first randomized controlled trial of benzodiazepine agonist treatment for benzodiazepine dependence. The research project will assess efficacy and safety of stabilizing treatment with prescribed benzodiazepines compared to benzodiazepine tapering and discontinuation regarding use of illicit benzodiazepines and accordingly well-being of patients with concurrent benzodiazepine and opioid dependence undergoing OAT. If the intervention is found to be efficacious and safe, it will be considered one of the options to standard treatment for this patient group.

Trial registration: EU trial number: EudraCT: 2021-004981-37. Registered on December 13, 2021.

Keywords: Benzodiazepines; Opioid agonist treatment; Polydrug use; Randomized controlled trial.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate {24}: The study is approved by regional ethical committee (Reference number 345516- REK Vest) and drug administration authorities in Norway and registered at www.clinicaltrials.gov. Written informed consent will be obtained from all the participants before commencing to the study. Consent for publication {32}: This manuscript does not contain individual personal data and the participants have given written informed consent for the publication of the study findings. Competing interests {28}: The authors declare that they have no cometing interests.

Figures

Fig. 1
Fig. 1
Flow-chart of the study procedures. Legend: Potential participants will be screened for eligibility. Individuals, who meet the eligibility criteria and provide written informed consent to participate, will be randomized either to a stabilizing dose with diazepam or oxazepam, or tapering using the same medications. The primary endpoint is at week 24 with a follow-up visit at week 52. OAT: opioid agonist treatment
Fig. 2
Fig. 2
Study sample size
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Vold JH, Skurtveit S, Aas C, Chalabianloo F, Kloster PS, Johansson KA, Fadnes LT. Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017. BMC Health Serv Res. 2020;20(1):352. - PMC - PubMed
    1. Votaw VR, Geyer R, Rieselbach MM, McHugh RK. The epidemiology of benzodiazepine misuse: A systematic review. Drug Alcohol Depend. 2019;200:95–114. - PMC - PubMed
    1. Abrahamsson T, Berge J, Ojehagen A, Hakansson A. Benzodiazepine, z-drug and pregabalin prescriptions and mortality among patients in opioid maintenance treatment-A nation-wide register-based open cohort study. Drug Alcohol Depend. 2017;174:58–64. - PubMed
    1. Liebrenz M, Boesch L, Stohler R, Caflisch C. Agonist substitution—a treatment alternative for high-dose benzodiazepine-dependent patients? Addiction. 2010;105(11):1870–4. - PubMed
    1. Waal H, Clausen T. Kan substitusjonsbehandling være et alternativ ved avhengighet av amfetamin/metamfetamin, kokain, cannabis og benzodiazepiner? Senter for rus-og avhengighetsorskning (SERAF). Oslo, 2020.https://www.med.uio.no/klinmed/forskning/sentre/seraf/publikasjoner/rapp....

Publication types

MeSH terms

LinkOut - more resources