REVIEW OF: Nosyk B et al, JAMA 2024;332(21):1822–1831; Naji L et al, BMJ Open 2025;15:e095645

STUDY TYPE: Two large cohort studies

Methadone and buprenorphine-naloxone remain frontline, life-saving treatments for opioid use disorder (OUD). Yet choosing between them for an individual patient is not always straightforward. Which medication is more likely to lead to success, and how should success be defined in the first place?

Nosyk and colleagues chose to compare dropout rates between patients on methadone versus buprenorphine-naloxone. They followed nearly 31,000 adults starting either methadone or buprenorphine-naloxone between 2010 and 2020. At two years, dropout was common with both, but slightly and statistically significantly higher for buprenorphine-naloxone (89% vs 82%). The difference in retention was similar before and after fentanyl became widespread. Overall mortality was low and similar between groups.

In contrast, Naji and colleagues focused on a different outcome: the ability of each medication to reduce ongoing opioid use. They looked at 2,600 adults in maintenance treatment and found that both medications worked about equally well at reducing nonprescribed opioid use. Interestingly, among patients without a history of injection drug use, methadone was associated with slightly higher odds of continued illicit opioid use compared with buprenorphine-naloxone. As in the Nosyk study, those taking methadone were more likely to stay in treatment at one year.

CARLAT TAKE
If your goal is to keep patients in care, methadone has a slight edge. For patients without a history of injection drug use, buprenorphine-naloxone may be a better choice. But this is splitting hairs; both medications are effective, and the best choice is the one your patient is willing to take and able to continue.