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

This is the primary outcomes article for CTN-0050.

This study, a long-term follow-up of patients from the NIDA Clinical Trials Network’s Starting Treatment with Agonist Replacement Therapy (START, CTN-0027), aimed to compare long-term outcomes among participants randomized to buprenorphine (BUP) or methadone (MET), including mortality, opioid use status during/after 60-month follow-up, treatment participation status and retention over the 60-month period, and the effects of each type of opioid replacement treatment (BUP or MET) on level of opioid use over the 60-month period. Follow-up was conducted in 2011-2014 on 1,080 opioid-dependent participants entering 7 opioid treatment programs in the US between 2006-2009 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.

Analysis revealed no difference in mortality between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died, versus 26 (5.8%) of 450 randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone (42.8% vs. 31.7% positive opioid urine specimens; 5.8 days vs. 4.4 days of past 30-day heroin use). Opioid use over the follow-up period by randomization condition was also significant, mostly due to less treatment participant 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. This study, the first to follow opioid dependent individuals randomized to two opioid maintenance treatments prospectively over 5 or more years, is instructive about longer term outcomes and poses a challenge to the field to enhance retention in the opioid maintenance treatment. Many individuals with opioid use disorder cycle in and out of maintenance treatment, and this study confirms they show better outcomes when retained in that treatment instead. Efforts are needed, especially in the context of the current opioid epidemic, to improve both BUP and MET treatment retention.

Related protocols: CTN-0027, CTN-0050