Naltrexone compares favorably to buprenorphine-naloxone, with a catch
STUDY: Mert A et al, Am J Drug Alcohol Abuse 2026
STUDY TYPE: Systematic review and meta-analysis of randomized trials
FUNDING: Independent
Background
Buprenorphine-naloxone (eg, Suboxone) and naltrexone ER injectable (Vivitrol) are both approved for opioid use disorder but work in opposite ways. The first is a partial opioid agonist, while the second is a full antagonist that blocks opioids effects and requires patients to be 7 to 10 days opioid-free before starting it. This meta-analysis pooled randomized trials comparing the two head-to-head.
The Study
- 5 randomized trials, 1,043 adults and adolescents with opioid use disorder (512 naltrexone, 531 buprenorphine-naloxone)
- Outcomes: treatment initiation, retention, relapse, urine tests, use days, and adverse events
- Follow-up ranged from 12 to 36 weeks
Results
Far fewer patients started naltrexone than buprenorphine (73% fewer), likely due to the abstinence requirement. Once started, retention, relapse, and self-reported days of opioid use didn’t differ between them.
Overall, retention, relapse, and safety about equal. Naltrexone lead to fewer opioid-positive urine tests (OR 0.52).
The maximum follow up was 36 weeks, and trials included a variety of patients: adolescents, HIV clinics, comorbid alcohol use
The Catch
This study didn’t look at overdose rates, but those may be slightly lower with buprenorphine-naloxone. In a new target-trial-emulation study, buprenorphine-naloxone was associated with lower 24-week nonfatal overdose (11.6% vs 13.9%). It’s likely this study was too new for inclusion in the analysis.
Side Effects
Adverse events, overdose, and deaths didn’t differ, though trials were underpowered for rare outcomes.
Limitations
Evidence certainty was low to very low for most outcomes; only initiation and retention reached moderate certainty.
Trials were few (5), blinding not possible (naltrexone is an injection), and populations varied (adolescents, HIV clinics, comorbid alcohol use). Many of the findings (initiation, relapse, and use-day findings) were sensitive to removing the largest trial.
Practice Implications
- Naltrexone injection may suit a patient who has already detoxed who wants to avoid an opioid agonist, but buprenorphine can get them into care faster.
- Naltrexone has additional benefits for comorbid alcohol use disorders.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
