Exploring the utility and safety of benzodiazepine prescribing among people receiving Opiate Replacement Therapy in Scotland: a multicentre retrospective cohort study

Escalating Scottish DRD are strongly associated with increasing use of benzodiazepines (BZD) often in combination with other drugs. Combinations of drugs associated with DRD increasingly include diverted prescribable BZDS (e.g. medical valium) and unprescribable, illicitly produced BZDs (e.g. etizolam) plus heroin or methadone. Scottish evidence suggests that people self-medicate with illicit BZDs to manage anxiety and depression. Rights, Respect and Recovery, the current drug and alcohol strategy, expressed Scottish Government concern regarding the increased prevalence and potency of BZD-type drugs.

Guidance on the clinical management of drug misuse and dependence states that pharmacological interventions may have a role in BZD dependence, but acknowledges there is little evidence to support long term substitute prescribing to reduce the associated harms. A 2018 Cochrane review concluded “it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate BZD discontinuation in chronic BZD users.” Public Health England have noted the lack of high-quality research in the last 10 years. There is evidence of harms associated with BZD prescribing among patients receiving Opiate Replacement Therapy (ORT). However conflicting evidence from case reviews of people on ORT prescribed a substitute BZDs, found lower mortality, and increased engagement in treatment.

Some Scottish addiction prescribers are increasingly exploring the utility of prescribing maintenance doses of BZDs in ORT patients to remove the risks associated with use of illicit BZDs (with unknown constituents and potency) and to increase retention in care. Anecdotal information from prescribers indicates that this approach is providing to be acceptable, effective, and safe for patients, but no research has been undertaken so far.

We propose to undertake a multisite cohort study of 1,350 ORT patients managed in specialist addition care services to compare outcomes among those prescribed BZDs (exposed) versus those not prescribed BZDs (unexposed). The cohort size was generated from a power calculation informed by the literature.

The primary outcome of interest will be all-cause mortality. Secondary outcomes include drug-related death, retention in care, evidence of illicit drug use, overdose and hospitalisation.