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Meta-Analysis
12 January 2026

Effectiveness and safety of therapies for patients with opioid use disorder: a systematic review and network meta-analysis

Authors: Madhusudan Kabra https://orcid.org/0000-0001-5089-9892 [email protected], Tushar Srivastava, Raju Gautam, Janharpreet Singh, Juha Oksanen, Tim MacDonald, Kenneth Lee, Brent Boyett, Bill Santoro, Anurag Gupta, Anne De Jong-Laird, and Shijie RenAuthor Info & Affiliations
Volume 15, Number 2
https://doi.org/10.57264/cer-2025-0171
PDFFormats

Abstract

Aim: Opioid use disorder (OUD) leads to significant morbidity and mortality. While opioid agonist therapies like transmucosal buprenorphine and methadone are effective, they face challenges such as poor adherence, diversion risk and suboptimal abstinence rates, prompting the development of long-acting injectable (LAI) buprenorphine. However, comparative evidence among LAIs and versus standard treatments remains limited. The aim of this study is to provide comparative evidence among buprenorphine LAIs and versus oral opioid agonist treatments. Materials & methods: We conducted a systematic literature review and network meta-analysis (NMA) evaluating the effectiveness and safety of LAI buprenorphine treatments (extended-release buprenorphine [BUP-XR; monthly injection] and other BUP-LAI [weekly and monthly injection]) versus transmucosal buprenorphine, methadone and buprenorphine implants in adults with OUD. The review included randomized controlled trials (RCTs) and non-RCTs for LAIs (January 2012 and March 2025). Primary outcomes were treatment discontinuation and illicit opioid use. Secondary outcomes were safety and health-related quality of life. Data were synthesized using univariate NMAs, bivariate NMA with surrogate end point modelling. Studies with limited data and single-arm designs were incorporated by using study-level matching techniques. Results: Ninety-eight studies met the inclusion criteria. BUP-XR demonstrated the highest probability of achieving treatment retention and opioid abstinence across analyses. In combined evidence (RCTs and non-RCTs), BUP-XR showed significantly lower risk of illicit opioid use versus transmucosal buprenorphine (rate ratio [RR] 1.99; 95% credible interval [CrI]: 1.29–3.11) and methadone (RR: 2.66; 95% CrI: 1.40–3.56). BUP-XR showed borderline significantly lower risk of illicit opioid use versus other BUP-LAI (RR: 1.81; 95% CrI: 0.97–3.55) and buprenorphine implant (RR: 2.28; 95% CrI: 0.98–5.38). Treatment discontinuation rates were similar between OUD treatments. Safety outcomes were generally comparable across treatments. Health-related quality of life indicated better recovery among patients treated with BUP-XR. Conclusion: BUP-XR may enhance treatment retention and abstinence over other OUD therapies, supporting its integration into clinical pathways. The results may help guide future updates to OUD treatment guidelines and policies aimed at optimizing the use of long-acting formulations. Additional research is needed to better define the comparative effectiveness of LAIs.

Plain language summary

What is this article about?

This article reviews and compares how well different treatments work for people with opioid use disorder. It focuses on buprenorphine long-acting injectables, a newer type of treatment designed to improve adherence and reduce misuse compared with daily opioid agonist therapies such as methadone and oral buprenorphine. The study combines evidence from both clinical trials and real-world studies using a systematic literature review and network meta-analysis.

What were the results?

The analysis included 98 studies. Monthly injectable buprenorphine (BUP-XR) showed the highest likelihood of helping people stay on treatment and avoid illicit opioid use compared with methadone, oral buprenorphine and other long-acting formulations. Safety was generally similar across all treatments, and people treated with monthly injections reported better quality of life during recovery.

Why is this important?

Opioid use disorder remains a major global health issue, and many people struggle to remain on daily treatments. These findings suggest that monthly injectable buprenorphine could offer a more effective and convenient option, improving long-term treatment outcomes and supporting recovery in real-world settings.

Supplementary Material

File (supplementary materials.docx)

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