Weekly and Monthly Subcutaneous Buprenorphine Are Not Inferior to Daily Sublingual Buprenorphine for Treatment of Opioid Use Disorder

Buprenorphine is an opioid partial agonist with known efficacy across a range of outcomes including decreased overdose, illicit opioid use, HIV transmission, and increased treatment retention for individuals with opioid use disorder (OUD). Until recently, buprenorphine with or without naloxone was only available in sublingual formulations for daily use. Longer-term depot formulations (i.e., biodegradable subcutaneous devices that deliver the medication over time) may have advantages for adherence, diversion, and unintended exposures. This study was a multisite, double-blind, double-dummy, active-controlled phase-3 randomized non-inferiority trial of sublingual buprenorphine compared with weekly and monthly depot buprenorphine for 24 weeks among 428 participants with moderate to severe OUD.

• Subcutaneous buprenorphine treatment was not inferior to sublingual buprenorphine treatment for both primary endpoints:
  • Response rates (no evidence of illicit opioid use for 8 of 10 time-points) were 14% for sublingual buprenorphine and 17% for subcutaneous buprenorphine.
  • Proportion of opioid-negative urine tests were 28% for sublingual buprenorphine and 35% for subcutaneous buprenorphine.

Comments: Although the response rates were low, these data support depot buprenorphine as an additional treatment option for individuals with moderate to severe OUD. Cost, insurance coverage, and restrictions on which pharmacies can dispense depot buprenorphine may impact adoption. Further work is needed to understand if depot buprenorphine provides theorized benefits for adherence and diversion in different patient populations.

Marc R. Larochelle, MD, MPH

Reference: Lofwall MR, Walsh SL, Nunes EV, et al. Weekly and monthly subcutaneous buprenorphine depot formulations vs daily sublingual buprenorphine with naloxone for treatment of opioid use disorder: a randomized clinical trial. JAMA Intern Med. 2018;178(6):764-773.