Methadone shows significantly higher treatment retention than buprenorphine-naloxone in patients with Opioid Use DisorderMethadone beats buprenorphine for opioid treatment retention

UNLABELLED: 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. 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 I statistic. 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; I = 62.2%). Attrition was higher in the buprenorphine-naloxone group (OR 2.47; 95% CI 1.42-4.30; I = 68.4%). In contrast, serious adverse events occurred less frequently with buprenorphine-naloxone (OR 0.72; 95% CI 0.48-1.09; I = 0.0%). 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.