REVIEW OF: Shiwach R et al, JAMA Netw Open 2025;8(10):e2537319; Shiwach R et al, JAMA Netw Open 2025;8(12):e2548043

STUDY TYPE: RCT

The rise of fentanyl and its derivatives has forced us to rethink how best to use buprenorphine, both how to initiate it and what doses are most effective for maintenance. Traditionally used as a sublingual film or tablet containing naloxone, buprenorphine is now available in several long-acting injectable formulations, creating opportunities for new treatment approaches. Two linked trials using extended-release injectable buprenorphine (Sublocade) examined whether patients can be transitioned quickly to injectable treatment, and once there, what dose works best.

In the first trial (n = 729), patients were randomized to rapid induction (a 4 mg sublingual dose followed an hour later with a 300 mg injection) versus a standard 7-day sublingual induction prior to injection. Both groups received a second 300 mg injection 1 week later. Participants who completed both injections were then enrolled in a companion maintenance trial (n=436), where they were randomized to receive 100 mg versus 300 mg injections monthly for 8 additional months.

The first trial found that rapid induction was associated with improved early retention: 66% of patients in the rapid-induction group received a second injection versus 54% in the standard-induction group. This advantage was even more pronounced among fentanyl-positive participants. In the maintenance trial, overall response rates were similar between doses. However, the higher 300 mg dose showed an advantage among those with heavier fentanyl use; participants using fentanyl daily or at least 14 times per week had an 11%–15% higher response rate with the 300 mg dose compared to the 100 mg dose.

Though compelling, remember that injectable buprenorphine remains substantially more expensive than sublingual formulations and often requires prior authorization, specialty pharmacy distribution, and reliable follow-up for monthly visits, all of which may limit access.

CARLAT TAKE
For patients using fentanyl, rapid transition to long-acting injectable buprenorphine was associated with improved early engagement. While 100 mg is a reasonable maintenance dose for some, those with heavy fentanyl use may benefit from 300 mg. Cost and access remain significant barriers, but for high-risk patients cycling through relapse, faster induction and higher maintenance dosing may be worth pursuing.