Clinical outcomes of benzodiazepine prescribing for people receiving opioid agonist treatment: a systematic review of the evidence

Many countries are experiencing increased use of unregulated benzodiazepines in combination with opioids and other drugs, which contributes to drug-related harm. This descriptive review identifies and synthesises outcomes of studies of co-prescribing benzodiazepines and opiates. A systematic review was undertaken in Medline, CINAHL, PsychInfo, Embase, and the Cochrane database covering publications from 01/01/1991‒18/11/2021. Inclusion criteria were: peer reviewed, English language studies of adults prescribed opioid replacement treatment and a concurrent benzodiazepine, and reporting outcome data. Of 4370 titles screened, 18 papers were included. The main outcomes identified covered all-cause mortality (ACM) (n=5); Overdose death (n=3); Retention in treatment (n=7); Hospitalisation/emergency care (n=2). Other outcomes included QTc interval, cognitive function, illicit drug use and mental health. Prescription of benzodiazepines alongside ORT increases ACM by 75-90%, evidence on overdose death is less robust but indicative of increased risk (40-334%). There was an indicative positive effect on treatment retention with increased retention in those prescribed a benzodiazepine with ORT compared to those not prescribed or taking non-prescribed benzodiazepine. In conclusion there is a growing body of evidence from methodologically robust epidemiological studies. Such studies are subject to confounders e.g. psychiatric co-morbidity so an RCT is recommended.