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