Proposed network meta-analysis aims to establish evidence hierarchy for non-pharmacological opioid use disorder interventionsComparing Non-Pharmacological Treatments for People with Opioid Use Disorder

Frontiers in Medicine Published September 16, 2026 DOI ↗ Editorial oversight: Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

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Key Takeaway

Note that this is a study protocol; no results are available to inform clinical practice at this time.

This publication is a protocol for a systematic review and network meta-analysis. It outlines the planned methodology to evaluate non-pharmacological interventions (NPIs) for adult patients with opioid use disorder, comparing them against standard pharmacological care such as methadone or buprenorphine, or other active NPIs. The primary outcomes of interest include abstinence, craving, and treatment retention, with secondary outcomes including relapse rates, anxiety, depression, and sleep quality.

The proposed analysis intends to use the GRADE framework to structure these non-pharmacological interventions into hierarchical clinical tiers based on evidence certainty. The ultimate goal is to provide a standardized foundation for individualized clinical care for patients with opioid use disorder.

Because this is a protocol, no results, sample sizes, or specific data points are currently available. The study has not been conducted, and therefore no conclusions regarding the efficacy or safety of the interventions can be drawn at this time. The clinical relevance lies in the future establishment of an evidence hierarchy for non-pharmacological management options.

How this fits prior evidence

This protocol addresses a gap in the evidence hierarchy for non-pharmacological opioid use disorder management. It builds upon existing evidence regarding pharmacological treatments, such as the finding that methadone is associated with higher treatment retention than buprenorphine-naloxone. While previous coverage noted the role of methadone in pain management and the impact of the Opioid Wizard on clinician confidence, this proposed meta-analysis seeks to specifically structure non-pharmacological interventions into clinical tiers.

Doctors are planning a large study to compare different ways to treat opioid use disorder. While many people currently use medications like methadone or buprenorphine, this study looks at non-drug options like counseling or behavioral therapy.

The goal is to see which non-drug methods help patients stay in treatment longer and reduce cravings. The researchers will also look at how these methods affect feelings of anxiety, depression, and sleep quality.

Because there are many different types of therapy available, the study aims to rank them by how well they work. This will help doctors choose the best personalized plan for each patient based on the strongest evidence available.

Since this is a plan for a future study, no final results are available yet. Once finished, the results will help create a clear guide for doctors to provide better care for people struggling with opioid addiction.

What this means for you:

This planned study aims to rank non-drug treatments to help doctors provide better care for opioid use disorder.

Common questions

What is a network meta-analysis?

It's a way of combining results from many studies to compare several treatments at once, even if they were never tested head-to-head. This plan will use that method to rank non-drug approaches for opioid addiction.

Does this study have results yet?

No. This is only a protocol, a plan for how the research will be done. The analysis hasn't been conducted, so there are no findings to report yet.

What treatments are being compared?

The plan will look at non-pharmacological interventions, like therapy or exercise, and compare them to standard medications such as methadone and buprenorphine, as well as to each other.

Who does this research focus on?

It will include adults with opioid use disorder. The goal is to help doctors and patients understand which non-drug options might work best alongside or instead of medication.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedSep 2026

View Original Abstract ↓

IntroductionNon-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.Methods and analysisPubMed, 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.JustificationThis 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.Trial registrationhttps://www.crd.york.ac.uk/PROSPERO/recorddashboard, PROSPERO CRD420261330214.

Proposed network meta-analysis aims to establish evidence hierarchy for non-pharmacological opioid use disorder interventionsComparing Non-Pharmacological Treatments for People with Opioid Use Disorder

How this fits prior evidence

Common questions

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Proposed network meta-analysis aims to establish evidence hierarchy for non-pharmacological opioid use disorder interventionsComparing Non-Pharmacological Treatments for People with Opioid Use Disorder

How this fits prior evidence

Common questions

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