Evaluating comparative effect of non‐pharmacological interventions adjunctive to opioid agonist therapy for opioid use disorder: A systematic review with network meta‐analysis

BACKGROUND AND AIMS: Non-pharmacological therapies are critical for disease management, particularly when pharmacological approaches are limited. Investigating their role as adjuncts to pharmacotherapy to improve outcomes in opioid use disorder (OUD) is of substantial clinical importance. This study aimed to evaluate the efficacy of non-pharmacological therapies as adjuncts to opioid agonist therapy (OAT) management for OUD. METHODS: We systematically searched PubMed, Cochrane Controlled Register of Trials, Embase and Web of Science from inception to 8 February 2025 for randomized controlled trials (RCTs) comparing OAT alone versus OAT combined with non-pharmacological interventions in OUD. Outcomes of interest included treatment retention assessed via odds ratios (ORs), negative urine test results (specimen and the longest duration of continuous drug abstinence) and opioid craving scores both evaluated via standard mean differences (SMDs). Bayesian network meta-analysis (NMA) using a random-effects consistency model was conducted to compare the relative effects of all non-pharmacological interventions. Local inconsistency was evaluated through node-splitting analysis, and global inconsistency was assessed using the non-consistency model. The certainty of the evidence was assessed using the GRADE framework (Grading of Recommendations, Assessment, Development and Evaluation) for network meta-analysis. RESULTS: Forty-two RCTs involving 5113 participants were included. For treatment retention, contingency management (CM) combined with OAT likely results in an increase low-certainty evidence; OR = 1.64, 95% credible interval (CrI) = 1.03-2.57, while the combination of OAT with contingency management plus cognitive behavioral therapy (CBT + CM; very low-certainty evidence; OR = 2.47, 95% CrI = 1.10-5.67) or with enhanced methadone services (EMS; very low-certainty evidence; OR = 5.48, 95% CrI = 1.47-22.61) may result in an increase, compared with OAT alone. No intervention statistically significantly improved opioid-negative urine tests over OAT alone (very low certainty). For craving, acupuncture (very low certainty; SMD = -2.13, 95% CrI = - 3.09 to -1.15) and sham acupuncture (low certainty; SMD = -1.49, 95% CrI = - 2.69 to -0.31) combined with OAT may reduce craving scores. CONCLUSION: Contingency management, as adjunctive therapies for opioid agonist therapy (OAT), may improve treatment retention in patients with opioid use disorder compared with traditional OAT. Enhanced methadone services and contingency management plus cognitive behavioral therapy may improve treatment retention too but the evidence is very uncertain. Compared with OAT, sham acupuncture as an adjunct therapy may help reduce opioid cravings; acupuncture may reduce cravings too but evidence is very uncertain.