What is the Best Dosing Strategy for Buprenorphine or Methadone to Prevent Relapse?

  • Buprenorphine-naloxone and methadone are highly effective treatments for opioid use disorder.
  • Having a “high enough” dose of these medications is important to prevent relapse, but what IS a “high enough” dose?
  • This study compared 4 different dosing approaches by examining data from 3 different NIDA CTN studies.
  • For buprenorphine-naloxone, increasing the dose weekly until a target minimum dosage was reached and then increasing it again in response to any opioid use was the most effective. For methadone, that same approach, or either part of it alone, were equally effective at reducing relapse to opioid use.


Opioid use disorder (OUD) continues to be a leading cause of death and illness in the U.S. Two of the most effective treatments for OUD are buprenorphine-naloxone (BUP-NX) and methadone.

Although providers know that having a “high enough” dose of buprenorphine or methadone is important, less is known about what that dose might be or how it should be attained. 

Stacked pills

Key points:

Researchers for this study used data from three NIDA Clinical Trials Network (CTN) studies about opioid use disorder treatment: CTN-0027, CTN-0030, and CTN-0051, to examine the risk of relapse under 4 different dosing strategies (separately for BUP-NX and methadone):

  1. dose is increased in response to participant-specific opioid use
  2. dose is increased weekly until some minimum threshold dose is reached
  3. dose is increased until some minimum threshold dose is reach and then increased in response to opioid use thereafter (the “hybrid” strategy, combining 1 + 2)
  4. dose is held constant after week 2 of treatment.

Examining the data, researchers found that for BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse.

For methadone, holding the dose constant resulted in the worst outcomes and the other 3 strategies (1-3 above) performed equally well. For example, the hybrid strategy reduced week 12 relapse risk by 13% for BUP-NX and by 20% for methadone, as compared to holding the dose constant.

Conclusions: In this study, patients taking BUP-NX for OUD had the lowest risk of relapse when their dose was increased weekly until a target dose was reached, and then increased again in the future in response to a recurrence of opioid use. For patients on methadone, the hybrid approach or either approach alone worked equally well and much better than holding the dose constant after 2 weeks of treatment. There may not be a single best dosing strategy for all patients, however these findings support a clinical recommendation that doses be targeted toward a minimum threshold and, in the case of BUP-NX, be raised again any time patients continue using opioids. 

Find it in the CTN Dissemination Library.

Rudolph KE, et al. Buprenorphine & methadone dosing strategies to reduce risk of relapse in the treatment of opioid use disorder. Drug and Alcohol Dependence 2022;239:109609. Find it in the CTN Dissemination Library.