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Randomized Controlled Trial
. 2025 Apr 1;185(4):372-381.
doi: 10.1001/jamainternmed.2024.8361.

Buprenorphine, Pain, and Opioid Use in Patients Taking High-Dose Long-Term Opioids: A Randomized Clinical Trial

William C Becker  1   2 , Karen H Seal  3   4   5 , David B Nelson  6   7 , Beth M DeRonne  6 , Allyson M Kats  8 , Benjamin J Morasco  9   10 , Joseph W Frank  11   12 , Una E Makris  13   14 , Jacob T Painter  15   16 , Kelli D Allen  17   18   19 , Amanda S Mixon  20   21 , Amy Bohnert  22   23 , Thomas E Reznik  24 , Hildi J Hagedorn  6   25 , Patrick Hammett  6   7 , Brian Borsari  3   5 , Catherine Baxley  3   5 , Erin E Krebs  6   26 ; VOICE Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Buprenorphine, Pain, and Opioid Use in Patients Taking High-Dose Long-Term Opioids: A Randomized Clinical Trial

William C Becker et al. JAMA Intern Med. .

Abstract

Importance: Guidelines recommend dose reduction or discontinuation of long-term opioid therapy when harm outweighs benefit, but strategies to help patients do so are limited.

Objective: To test optionally switching to buprenorphine as a strategy for improving pain and reducing opioids among patients prescribed high-dose, full agonist long-term opioid therapy.

Design, setting, and participants: In this pragmatic, multisite, 12-month randomized clinical trial with masked outcome assessment, patients treated at Veterans Affairs primary care clinics were recruited from October 2017 to March 2021, with follow-up completed June 2022. Eligible patients had moderate to severe chronic pain despite high-dose opioid therapy (≥70 mg/d for at least 3 months). Patients were randomized to having the option to switch to buprenorphine or not having the option to switch.

Interventions: The buprenorphine option was discussed with eligible patients as part of a larger trial of collaborative pain care interventions. Those who switched had structured follow-up to optimize dosing and address adverse effects.

Main outcomes and measures: The primary outcome was Brief Pain Inventory total score at 12 months. The main secondary outcome was opioid dose in morphine milligram equivalents at 12 months.

Results: Of 207 included participants, 185 (89.4%) were male, and the mean (SD) age was 60.9 (10.2) years. A total of 104 were randomized to the buprenorphine option and 103 to the no buprenorphine option. In the buprenorphine option arm, 27 participants (26.0%) switched. Over 12 months, the mean (SD) Brief Pain Inventory score improved from 6.8 (1.5) to 6.1 (1.9; adjusted mean difference [AMD], -0.59; 95% CI, -0.89 to -0.29) in the buprenorphine option arm and from 6.8 (1.6) to 6.3 (1.7; AMD, -0.50; 95% CI, -0.81 to 0.20) in the no option arm (between-group AMD, -0.09; 95% CI, -0.52 to 0.34). Over 12 months, mean (SD) opioid dosage decreased from 157 (75) mg/d to 94 (98) mg/d in the buprenorphine option arm (AMD, -61.0 mg/d; 95% CI, -74.1 to -47.9) and from 165 (88) mg/d to 107 (89) mg/d (AMD, -58.5 mg/d; 95% CI, -71.6 to -45.4) in the no option arm (between-group AMD, -2.5 mg/d; 95% CI, -21.1 to 16.0).

Conclusions and relevance: In this trial, outcomes did not differ between groups; both had small improvements in pain and substantial reductions in opioid dosage, but the proportion of participants who switched to buprenorphine was low.

Trial registration: ClinicalTrials.gov Identifier: NCT03026790.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Seal reported serving on the National Institutes of Health–Department of Defense–Department of Veterans Affairs Pain Management Steering Committee. Dr Morasco reported research funding from the National Institutes of Health. Dr Frank reported research funding from the VA Health Systems Research, VA Office of Rural Health, and the National Institutes of Health; and serving on a data safety monitoring board for National Institutes of Health. Dr Makris reported payments from the University of Alabama and the Winter Rheumatology Symposium for presentations; and serving on data safety monitoring boards for National Institute on Aging trials. Dr Bohnert reported payment for serving as an expert witness for the Attorney General of Michigan in a lawsuit against opioid distributors. Dr Borsari reported research funding from the Department of Veterans Affairs and the National Institutes of Health and receiving consulting fees from the National Institutes of Health. Dr Baxley reported grants from Patient-Centered Outcomes Research Institute paid to her institution during the conduct of the study. Dr Krebs reported research funding from the Department of Veterans Affairs and the National Institutes of Health; travel expense reimbursement from the American College of Physicians, the Foundation for Opioid Response Efforts, and the US Association for the Study of Pain; serving as a member of the Foundation for Opioid Response Efforts Scientific Advisory Council; and funding from Origin Editorial for serving as Associate Editor for Patient-Centered Outcomes Research Institute research reports. No other disclosures were reported.

Comment on

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