Buprenorphine-naloxone vs methadone for opioid use disorder: a systematic review and meta-analysis of randomized clinical trials.

Background: This meta-analysis evaluated the efficacy and safety of buprenorphine-naloxone compared to methadone in the treatment of Opioid Use Disorder (OUD), with a focus on treatment retention, attrition rates, and serious adverse events. OUD remains a major public health concern, necessitating effective pharmacological interventions to improve adherence and minimize adverse outcomes.Methods: A systematic search of PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus identified randomized controlled trials comparing both treatments. The study adhered to PRISMA guidelines, and data were analyzed using a random-effects model with Odds Ratios (OR) and 95% Confidence Intervals (CI). Heterogeneity was assessed using the I² statistic.Results: Seven randomized controlled trials involving 3,622 patients were included. Methadone doses ranged from 5 to 397 mg/day and buprenorphine-naloxone from 2 to 32 mg/day. Methadone showed significantly higher treatment retention at six months compared to buprenorphine-naloxone (OR 0.43; 95% CI 0.27-0.67; I² = 62.2%). Attrition was higher in the buprenorphine-naloxone group (OR 2.47; 95% CI 1.42-4.30; I² = 68.4%). In contrast, serious adverse events occurred less frequently with buprenorphine-naloxone (OR 0.72; 95% CI 0.48-1.09; I² = 0.0%).Conclusion: In conclusion, methadone is associated with superior retention, while buprenorphine-naloxone presents a more favorable safety profile. These findings highlight the need for individualized treatment decisions based on clinical context and patient-specific risks. Future large-scale, high-quality studies are recommended to guide optimal pharmacological strategies for managing OUD.

Registration: PROSPERO protocol number: CRD 42025634919.