Systematic Review of the Safety and Tolerability of Injectable Prolonged-Release Buprenorphine (Buvidal) in Adults With Opioid Dependence

AIMS: Widely available opioid substitute treatments have numerous limitations including the potential for non-compliance, misuse, diversion and accidental overdose. The advent of a prolonged-release, injectable form of buprenorphine may be the solution to overcoming these issues, as well as reducing the intrusion on the patient's daily life. Initial trials have shown success in achieving a significantly higher percentage abstinence compared to placebo. This systematic review and meta-analysis will examine efficacy, safety and tolerability data. METHODS: A systematic review and meta-analysis, including all randomised controlled trials reporting raw data on efficacy, safety and side effects of injectable buprenorphine. Included articles were identified using PubMed, Ovid (EMBASE and MEDLINE), Google Scholar and Cochrane Library. Participants were either community outpatients or hospital inpatients, aged over 18 years, with opioid use disorder. Interventions were prolonged-release injectablebuprenorphine of any preparation or dosing schedule, compared to a control such as sublingual buprenorphine or placebo. The primary outcome measure was treatment efficacy, specifically treatment retention and negative urine drug screen results. The secondary outcomes measures were drug related adverse events, severe adverse events, nonfatal serious adverse events, mortality, discontinuation, and drug overdose. Six articles were selected for inclusion following assessment using our exclusion criteria. Study quality was assessed using the CASP tool and Cochrane Risk of Bias 2. Review Manager 5.4.1 was used for data synthesis. RESULTS: Our primary endpoint was efficacy, using treatment retention and negative urine samples as surrogate markers. Regarding treatment retention there was a statistically significant increase in the ‘Buvidal’ group compared to the control group (OR = 1.46, 95% CI = 1.12 to 1.89, P = 0.005). There was also a statistically significant increase in negative urine samples in the ‘Buvidal’ group compared to the control group (OR = 1.38, 95% CI = 1.26 to 1.52, P < 0.00001). We examined a number of secondary outcomes which focussed on safety and tolerability data. These showed no statistically significant differences between the two groups (drug overdose (OR = 0.09), drug related adverse events (OR = 1.75), severe adverse events (OR = 0.93), nonfatal serious effects (OR = 0.65), mortality (OR = 1.63) and discontinuation (OR = 1.52)). CONCLUSION: The studies have shown the efficacy of ‘Buvidal’ was statistically significant in comparison to the control groups, with no difference in their side effect profiles. To our knowledge, this is the first systematic review and meta-analysis of its kind, and our results support the hypothesis that ‘Buvidal’ is an effective and safe treatment for opioid use disorder.