The report is a product of the VA/HSR Evidence Synthesis Program.

Interventions for Co-Occurring Chronic Pain and Opioid Use Disorder

Takeaway: Evidence on the benefits and harms of interventions to treat co-occurring chronic pain and opioid use disorder (OUD) or self-reported potential prescription opioid misuse or dependence is limited. This review identified few studies, and most of these had substantial methodological limitations and small sample sizes. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, which included mindfulness training, cognitive re-appraisal skills, and positive emotion regulation, may be promising for these co-occurring conditions. Additional psychological therapies targeting distress tolerance and/or reward dysregulation may also be effective. Future research to address current evidence gaps and limitations should assess a common set of outcome measures and enroll larger samples. Research is needed to address adherence and retention in initiation and stabilization of medications for OUD. In addition, future research should evaluate health system outcomes (e.g., access barriers and facilitators, healthcare use, staff resources, and costs) and identify key elements and optimal dosing of integrated psychotherapy interventions. An update of this review in the next three to five years could evaluate a substantially expanded evidence base, as 23 potentially eligible trials are in progress.

Chronic pain and opioid use disorder (OUD) commonly co-occur, in part due to long-term opioid therapy prescriptions for pain. Co-occurrence of chronic pain and OUD can contribute to access and engagement challenges, leading to worse outcomes for affected individuals. In response to a request from HSR’s Pain/Opioid Consortium of Research (Pain/Opioid CORE), VA’s Office of Mental Health, and the VA Pain Management, Opioid Safety, and Prescription Drug Monitoring Program, HSR’s Evidence Synthesis Program (ESP) Center in Minneapolis reviewed the evidence on the benefits and harms of interventions for co-occurring chronic pain and OUD or self-reported potential prescription opioid misuse or dependence. To identify relevant studies, the ESP team searched MEDLINE, Embase, PsycINFO, and CINAHL databases from inception through August 5, 2025.

Summary of Findings

Overall:

• The 14 trials included in this review examined substantially different populations, interventions, and comparators. Most were small and rated as having some concerns or high risk of bias. All had relatively short-term follow-up (median of 16 weeks).
• Nine of the trials addressed chronic pain and OUD, three focused on chronic pain and self-reported potential prescription opioid misuse or dependence, and two included a mix of individuals with OUD or self-reported potential prescription opioid misuse or dependence. All studies of OUD populations included pharmacologic treatment (buprenorphine or methadone) for both the intervention and comparator groups.
• No studies examined health system outcomes such as access barriers and facilitators, healthcare use, staff resources, or costs.

Chronic pain and OUD:

• For medications for OUD initiation, the evidence is very uncertain on the effect of buprenorphine/naloxone on pain severity, opioid misuse, and adverse events, compared with methadone.
• There may be little to no difference in the mean number of days of illicit opioid use at 16 weeks for the Mindfulness-Oriented Recovery Enhancement (MORE) intervention, which included mindfulness training, cognitive re-appraisal skills, and positive emotion regulation, plus methadone, compared with methadone alone.
• Two trials reported that MORE plus methadone resulted in better pain outcomes compared to methadone alone; one of these trials also found that MORE plus methadone resulted in higher methadone adherence.
• One trial reported that there were no differences in pain and opioid outcomes between web-based cognitive behavioral therapy (CBT) plus methadone, compared with drug counseling plus methadone.
• One trial reported that yoga plus methadone or buprenorphine improved pain and opioid outcomes similarly to health education plus methadone or buprenorphine.
• One trial reported that massage plus methadone improved pain and opioid outcomes similarly to methadone alone.

Chronic pain and self-reported potential prescription opioid misuse or dependence:

• One trial reported improved pain and opioid outcomes, and one trial reported less opioid misuse in MORE compared with supportive psychotherapy.
• One trial reported less opioid misuse but no differences in pain outcomes when comparing web-based CBT plus usual care versus usual care.

Chronic pain and OUD or self-reported potential prescription opioid misuse or dependence:

• One trial evaluating low-dose versus standard buprenorphine initiation among hospitalized patients was terminated early and reported serious and non-serious adverse events among all participants.
• One trial reported better pain and opioid outcomes with Acceptance and Commitment Therapy plus mindfulness compared to usual care.

Implications

Evidence on the benefits and harms of interventions to treat co-occurring chronic pain and OUD or self-reported potential prescription opioid misuse or dependence is limited due to methodological concerns, including the small number of completed trials and the small sample size of most studies. MORE might be a promising therapy for chronic pain and co-occurring OUD or self-reported potential prescription opioid misuse or dependence; additional psychological therapies targeting distress tolerance and/or reward dysregulation may also be effective.

Limitations

The review was limited to English-language studies, and categorization of interventions and comparators depended on descriptions provided in published articles and trial registries.

Future Research

Future research to address current research gaps and methodological limitations should assess a common set of outcome measures and enroll larger sample sizes. Research is needed to operationalize and further define the emerging construct of self-reported potential prescription opioid misuse or dependence, which should help distinguish it from OUD and may be particularly relevant to treatment effects and optimization. Future studies should address recruitment, adherence, and retention related to medication treatment for OUD, particularly during initiation and stabilization. In addition, research is needed to evaluate health system outcomes (e.g., barriers and facilitators to care, healthcare use, staff resources, and costs) and to identify key elements and optimal dosing of integrated psychotherapy interventions. An update of this review in the next three to five years could evaluate a substantially expanded evidence base, as 23 potentially eligible trials are in progress.

Citation

Goldsmith ES, Landsteiner A, Ullman K, et al. Interventions for Co-Occurring Chronic Pain and Opioid Use Disorder: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Systems Research, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #09-009; 2026.

To view the full report, go to https://vaww.hsrd.research.va.gov/publications/esp/oud-chronic-pain.cfm (This report is available via intranet only.)

How can VA leadership work with the ESP? Nominations for systematic review topics may be submitted to the program at any time. When you submit a topic nomination form, ESP Coordinating Center staff will work with you to determine the appropriate research approach and ESP product to address your questions of interest. Topics are selected and assigned to an ESP Center based on program capacity and alignment with VA national goals.

This Management Brief is provided to inform you about recent HSR findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR Resource Center charged with disseminating important HSR findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers, and to disseminate these reports throughout VA.

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