Non-pharmacological interventions for opioid use disorder: protocol for a systematic review and network meta-analysis

Abstract

Non-pharmacological interventions (NPIs) are increasingly recognized as essential adjuncts to alleviate symptoms and enhance compliance in opioid use disorder (OUD). Although clinical guidelines recommend specific NPI modalities, high-quality evidence regarding their comparative hierarchies and time-course dynamics remains limited. We plan to conduct a systematic review and network meta-analysis (NMA) to evaluate and rank the efficacy of diverse NPIs. PubMed, Embase, CENTRAL, and CINAHL will be searched without language restrictions. We will include randomized controlled trials (RCTs) evaluating adult OUD patients randomized to commonly utilized NPIs versus standard pharmacological care (e.g., methadone, buprenorphine) or active alternative NPIs. Reviewer pairs will independently screen studies, extract data, and assess the risk of bias using the Cochrane RoB 2.0 tool, implementing a strict decision rule where failures in allocation concealment or missing data domains automatically trigger an overall high risk-of-bias judgment. Frequentist multivariate random-effects NMA (REML method) will be conducted to synthesize outcomes across primary (abstinence, craving, treatment retention) and secondary (relapse rates, anxiety, depression, sleep quality) endpoints. Node-splitting models and network meta-regressions will explore critical effect modifiers, focusing specifically on background pharmacological regimens and time-course treatment effects across distinct intervention timepoints. Finally, the GRADE framework will be implemented via a minimally contextualized approach to structure NPIs into hierarchical clinical tiers based on effect estimates and evidence certainty. This NMA will establish an evidence hierarchy for non-pharmacological OUD management by evaluating clinical efficacy and systematically stratifying optimal interventions based on their certainty of evidence (moderate-to-high versus low-to-very-low), thereby providing a standardized foundation for individualized clinical care and future trials. https://www.crd.york.ac.uk/PROSPERO/recorddashboard , PROSPERO CRD420261330214.