Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence

J Subst Abuse Treat. 2014 Oct;47(4):275-81. doi: 10.1016/j.jsat.2014.05.012. Epub 2014 Jun 10.


Opioid substitution treatment (OST) for opioid dependence may be limited by adverse events (AEs). Increasing the range of therapeutic options optimizes outcomes and facilitates patient management. An international, multi-center, two-phase study investigated the efficacy and safety of slow-release oral morphine (SROM) versus methadone in patients receiving methadone therapy for opioid dependence. In phase 1 (two way cross-over, 11 weeks each period) patients were randomized to SROM or methadone oral solution. In phase 2 (25 weeks), patients continued treatment with SROM (group A) or switched from methadone to SROM (group B). In total, 211 out of 276 completed phase 1 and 198 entered phase 2 (n=95 group A, n=103 group B). Treatment with both SROM and methadone was well tolerated. However, the mean QTc-interval associated with methadone was significantly longer than that under SROM. Higher treatment satisfaction, fewer cravings for heroin, and lower mental stress were reported with SROM. This study adds a significant further weight of evidence that SROM is an effective and well tolerated long-term maintenance treatment for opioid dependence with a beneficial risk profile compared to methadone regarding cardiac effects and supports its clinical utility.

Trial registration: NCT01079117.

Keywords: Opioid dependence; Opioid substitution treatment; QTc-interval; Safety; Slow-release oral morphine.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Europe
  • Female
  • Humans
  • International Cooperation
  • Male
  • Methadone / administration & dosage
  • Methadone / adverse effects
  • Methadone / therapeutic use*
  • Morphine / administration & dosage
  • Morphine / adverse effects
  • Morphine / therapeutic use*
  • Opiate Substitution Treatment*
  • Opioid-Related Disorders / drug therapy*
  • Treatment Outcome


  • Delayed-Action Preparations
  • Morphine
  • Methadone

Associated data

  • EudraCT/2008-002185-60