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

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

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.

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.

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.

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.

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).

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.

ClinicalTrials.gov Identifier: NCT03026790.