Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial

Addiction. 2016 Apr;111(4):695-705. doi: 10.1111/add.13238. Epub 2016 Jan 13.


Aims: To compare long-term outcomes among participants randomized to buprenorphine or methadone.

Design, setting and participants: Follow-up was conducted in 2011-14 of 1080 opioid-dependent participants entering seven opioid treatment programs in the United States between 2006 and 2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average 4.5 years.

Measurements: Outcomes were indicated by mortality and opioid use. Covariates included demographics, site, cocaine use and treatment experiences.

Findings: Mortality was not different between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone [42.8 versus 31.7% positive opioid urine specimens, P < 0.01, effect size (h) = 0.23 (0.09, 0.38); 5.8 days versus 4.4 days of past 30-day heroin use, P < 0.05, effect size (d) = 0.14 (0.00, 0.28)]. Opioid use during the follow-up period by randomization condition was also significant (F(7,39,600) = 3.16; P < 0.001) due mainly to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine.

Conclusions: There are few differences in long-term outcomes between buprenorphine and methadone treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in opioid use.

Keywords: Buprenorphine; longitudinal; methadone; mortality; opioid dependence; opioid use; outcomes.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Analgesics, Opioid / therapeutic use*
  • Buprenorphine, Naloxone Drug Combination / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Methadone / therapeutic use*
  • Middle Aged
  • Narcotic Antagonists / therapeutic use*
  • Opiate Substitution Treatment / methods*
  • Opioid-Related Disorders / drug therapy*
  • Random Allocation
  • Treatment Outcome
  • Young Adult


  • Analgesics, Opioid
  • Buprenorphine, Naloxone Drug Combination
  • Narcotic Antagonists
  • Methadone