Buprenorphine, Pain, and Opioid Use in Patients Taking High-Dose Long-Term Opioids
Authors: William C. Becker, Karen H. Seal, David B. Nelson, Beth M. DeRonne, Allyson M. Kats, Benjamin J. Morasco, Joseph W. Frank, Una E. Makris, Jacob T. Painter, Kelli D. Allen, Amanda S. Mixon, Amy Bohnert, Thomas E. Reznik, Hildi J. Hagedorn, Patrick Hammett, Brian Borsari, Catherine Baxley, Erin E. Krebs, Audrey Abelleira, Melissa Adams, Erin Amundson, Adam Anicich, Brett Ankawi, Stephanie Arnold, Anuj Aryal, David Atkins, Timothy Atkinson, Kristen Backe, Matthew Bair, Smita Bajpai, Kristeen Baller, Ann Bangerter, Monica Barbosa, Steven Barnett, Stephen Bartlett, Mary K. Bartnik, Joel Baskin, Ronald Blehm, Philip P. Bloechl, Natassia Boening, Nicole Boesch, Sondra Bolander, Marianne Bolf, John Bonchak, Karen Booth, Margaret Bordanea, Dominika Borowa, Marnie Bowden, Sara Britnell, Daniel Broderick, Carrie Bronars, Koren Brooks, Cheryl B. Brown, Erin Brudvik, Katrina Buchanan, Carolyn Buesgens, Michele Buonora, Rebekka Burch, Caitlin Burton, Sujata Bhushan, Celia A. Butler, Susan Byerly, Catherine Byrd, Gina Byrd, Emily Campbell, Desmond Cariveau, Suzanne Carmody, Medenna Carr, Thomas Carr, Dana Cervone, Michael Chandler, Kendra Clarke, Michael Clay, William B. Coy, Michael Craine, David Culver, Andrea Cutting, Alisher Dadabayev, David Daly, Rose Degerstrom, Angela L. Denietolis, Natasha DePesa, Paula Desmet, Amber Devlin, Dozie Dike, Chinedu Diokpa, Meenakshi Dogra, Karen Drexler, Anna Drum-Oden, Tina Duvall, Frances K. Eads, Sara N. Edmond, Edward Eichelsdoerfer, Christina Ellifritz, Jenna Ellison, Kimberly Erwin, Christi Escobedo, Lydia Feighner, Ashley Feuchs, Ashley Fike, Toni Finetti, Livia Franchina, John T. Freeman, Rebecca A. Frontera, Rachel Galvan, Caitlin Garvey, Sherrhonda Gayle, Courtney Givens, Rosie Glenn, Keely Godwin, Michael Goldstein, Kelly Gosselin, Stephen Graham, Kimberlea F. Grimm, Amitha Gumidyala, Christine Hagerman, Anne Hale, Levi M. Hall, Jacqueline Harden, Jeanette Hawkins, Stephanie Hepton, Ellen Herbst, Aleks Herynk, Brandon Heuermann, Nina Hidalgo, John Hoffmann, Christopher Holland-deguire, Kaydance Hope, Dana Horowitz, Andre Huang, Teresa Hudson, Katie F. Huffman, Neal E. Hunt, Stephanie Hyde, Kristi Jacobson, Agnes Jensen, Eric Johnson, Elzie Jones, Betty Kaiser, Kimberly Kauzlarich, Rahul Kavathekar, Robert Kerns, Rena Knutson, Tawny Kross, Pooja Lagisetty, Edward LaHaie, Sam Lahidji, Grace Le, Mira Lelovic, Martein Lewis, Sara Librodo, Erin Linden, David Lindsay, Lisa Lively-Brindley, Janet Lorenzo, Lisa Luciani, Cassie Lusk, Jill Mahal-Lichty, Patricia Maloy, Jennifer Manuel, Payal Mapara, Kimberly Marcolivio, Bradley Marcy, Lindsay Marek, Rebecca Marraffa, Bindu Mason, Nicole McCamish, Michael McKissack, Elaine Miller, Janis Moon, Heidi Morris, Jennifer Mundt, Jennifer Naylor, Mitchell Nazario, Angela Nelson, Angela Nichols, Esther Njau, Maureen Noh, Charlotte Nolan, Patricia Nolan, Sean Nugent, Joshua W. Oakley, Helen Ofstad, Jennifer Okere, Ronald L. Olney, Jed Olson, Veronica Ortolan, Jeffrey Osborne, Bruce Osler, Michele Packard-Milam, Sarah Palyo, Anjali Patel, Chelsea H. Wiener, Doris Peter, Michel Philippe, John Pinsonnault, Natalie Purcell, Saritha Reddy, Justin Reed, Nancy Rettmann, David Rezaei, Alyssa Roberti, Verona Robinson, Henri Roca, Eleni Romano, Tara Rosema, Robert Rouse, Paul Rozzero, Indulis Rutks, Raha F Sabet, Elijah Sacra, Nicole Sadowski, Hope Salameh, Friedhelm Sandbrink, Clarke Sauve, Kathryn A. Schopmeyer, Allison Schroeder, Megan Sculley, John Sellinger, Kenneth Sewell, Randy Seys, Mona Shah Barman, Pamela Sharpe, Tracy Sides, Kristin E. Silver, Malloree Siver, Jessica Sloan, Christine Smith, Elizabeth Son, Sean Stevens, Jennifer Stoll, Sandra Stoll, Thomas Stoner, Malcolm Strand, Jean A. Sumner, Bobby Surginer, Kaitlin Svabek, Gina Swanson, Carla Tappainer, Christina Tat, Brent C. Taylor, Alec Theis, Laura C. Thomas, Gay R Thomas, Kathryn Tiene, Randall Udouj, Ebonne Ugbo, Shaina R. Varughese, Shanti Venkatraman, Katherine Viera, Janet Walker, Jennifer Walker, Gloria Wang, Kayleen Watson, Erin Watson, William C. Westmoreland, Eileen Wilbur, Beth Williams, Alan Wolfman, Melinda Woloszyn, Joseph Zanga, Samara Zuniga
Journal: JAMA Internal Medicine (2025)

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