Yunyi Xiao, Miguel Ribeiro Ramos, Paul Montgomery-Marks
Background: The evidence is still sparse on the effects of various doses and routes of buprenorphine on emotional and clinical outcomes for individuals with OUD. Methods: A systematic review and meta-analysis of RCTs was performed following PRISMA and Cochrane guidelines. The electronic databases and other sources were searched for studies that were published from February 2013 to September 2025. Negative emotional symptomology, illicit opioid use, treatment retention, and adverse events were eligible outcomes. Standardized mean differences and odds ratios were used to summarize continuous and binary outcomes, respectively. Results: There were five RCTs that met the inclusion criteria. In studies comparing single-dose buprenorphine, a single dose of 96 mg was more effective than a single dose of 32 mg on negative emotional symptom scores (SMD = -0.66, 90% CI [-1.00, -0.32]). But limited evidence suggested that the odds of observing illicit opioid use were lower with subcutaneous buprenorphine than sublingual buprenorphine (OR = 0.61, 90% CI [0.39, 0.94]). There were no apparent differences between dose comparisons or administration-route comparisons with respect to adverse events. Levels of certainty of evidence were relatively low. Conclusions: Some limited data suggest there may be a correlation between the dose and route of buprenorphine administration and short-term emotional and illicit opioid-use outcomes. But the number of trials, the size of the samples, and methodological flaws significantly limit the validity and applicability of these results. It is worth emphasising that the high-dose comparisons featured in this review were from single doses in acute treatment settings, and thus are not suitable for extrapolating to everyday, maintenance doses.