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

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.