REVIEW OF: D’Onofrio G et al, JAMA Netw Open 2024;7(7):e2420702; Waters RC et al, JAMA Netw Open 2025;8(8):e2527016

STUDY TYPE: Nonrandomized feasibility trial; retrospective observational cohort

Starting buprenorphine can be tricky, especially when patients aren’t yet in clear withdrawal. Long-acting injectable formulations may reduce precipitated withdrawal risk and deliver treatment that lasts days to weeks. Two recent studies explore the safety and feasibility of this “direct-to-inject” approach.

D’Onofrio and colleagues examined whether buprenorphine could be started by injection before significant withdrawal developed. One hundred adults with opioid use disorder (OUD) presenting to the emergency department with low withdrawal scores (Clinical Opiate Withdrawal Scale [COWS] score of 0–7) were given a 24 mg injection of extended-release buprenorphine (Brixadi weekly), observed for 4 hours, and followed for 1 week. Precipitated withdrawal occurred in only 7%; 3% in those with COWS 4–7 and 14% in those with COWS 0–3. At 1 week, 73% had engaged in follow-up OUD care.

Separately, Waters and colleagues expanded on this approach by beginning with Brixadi weekly and transitioning to Brixadi monthly. Ninety-five adults received three consecutive injections, according to the following schedule:

• Day 1: 8 mg weekly injectable buprenorphine (Brixadi weekly)
• Day 2: 16 mg weekly injectable buprenorphine (Brixadi weekly)
• Day 3: 128 mg or 300 mg monthly injectable buprenorphine (Brixadi monthly or Sublocade)

Ninety percent initiated the protocol, 75% completed all three injections, and 64% received a second monthly dose. Some experienced mild withdrawal, most often after the monthly injection, but overall tolerability was acceptable.

CARLAT TAKE

These studies suggest buprenorphine induction can be done safely in patients with low withdrawal scores using long-acting injectables. A single Brixadi weekly injection provides therapeutic coverage for about a week; two weekly injections followed by a monthly formulation can transition patients to month-long coverage within three days. The data are short-term and uncontrolled, but for patients who may not return or cannot tolerate withdrawal, injectable buprenorphine is a reasonable way to begin treatment immediately and maintain therapeutic levels from day one.