REVIEW OF: Jutras-Aswad D et al, Am J Psychiatry 2022;179(10):726–739

STUDY TYPE: Open-label, pragmatic, noninferiority, randomized controlled trial

Buprenorphine/naloxone (BUP) and methadone are mainstays of opioid agonist therapy for opioid use disorder (OUD). But most of the data backing this up come from studies of patients who use heroin. It isn’t known how generalizable these findings are for patients using other opioids. Moreover, BUP is usually taken at home, whereas methadone tends to be closely supervised. Researchers in this study were interested in how closely supervised methadone treatment compares with flexibly dosed BUP for prescription-type OUD (POUD).

Researchers recruited participants with POUD and randomized them to receive BUP (n=107) or methadone (n=108). BUP was started between 4 mg/1 mg and 12 mg/3 mg per day, and methadone was started at 30 mg per day. The titration schedule of each medication and whether participants could have “take-home privileges” were decided at the discretion of the research staff. The study was a noninferiority trial, meaning that the analysis was designed to determine if BUP is at least as good as methadone for treating POUD. The primary outcome measure was opioid use determined by urine drug screens collected every two weeks for 24 weeks. 

The average maximum doses were 20.3 mg for BUP and 81.8 mg for methadone. Of the 107 who started BUP, 71 completed the 24 weeks; of the 108 who started methadone, 79 completed. Some of the participants (22% in the BUP group and 12% in the methadone group) chose to switch the medication they were receiving. 73% of the BUP group were able to take meds home, compared with 32% of the methadone group.

The primary outcome measure showed that, of the completers, 24% of the urine drug screens in the BUP group were drug-free, compared to 18.5% of the screens in the methadone group. Adverse reactions were minimal in both groups; most common (6%) were mild to moderate withdrawal symptoms.

The researchers concluded that flexibly dosed BUP, mostly taken at home, was at least as effective in treating POUD as closely supervised methadone treatment. There were more dropouts and medication switches in the BUP group, though a post-hoc analysis showed that the BUP group had more negative urine drug screens early in the trial, presumably because they were able to reach a therapeutic dose more quickly. 

CARLAT TAKE

Flexibly dosed BUP was at least as good as methadone for the treatment of POUD. BUP has the advantage of being easier to take at home and greater overall accessibility, but retention was slightly better with methadone. Given that both treatments emerged as viable, feel free to recommend either one for your patients with POUD.