title: Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone.
abstract: OBJECTIVE
  To compare the efficacy of slow-release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone.
  
  
  METHODS
  Prospective, multiple-dose, open label, randomized, non-inferiority, cross-over study over two 11-week periods. Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment.
  
  
  METHODS
  Fourteen out-patient addiction treatment centres in Switzerland and Germany.
  
  
  METHODS
  Adults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks.
  
  
  METHODS
  The efficacy end-point was the proportion of heroin-positive urine samples per patient and period of treatment. Each week, two urine samples were collected, randomly selected and analysed for 6-monoacetyl-morphine and 6-acetylcodeine. Non-inferiority was concluded if the two-sided 95% confidence interval (CI) in the difference of proportions of positive urine samples was below the predefined boundary of 10%.
  
  
  RESULTS
  One hundred and fifty-seven patients fulfilled criteria to form the per protocol population. The proportion of heroin-positive urine samples under SROM treatment (0.20) was non-inferior to the proportion under methadone treatment (0.15) (least-squares mean difference 0.05; 95% CI = 0.02, 0.08; P > 0.01). The 95% CI fell within the 10% non-inferiority margin, confirming the non-inferiority of SROM to methadone. A dose-dependent effect was shown for SROM (i.e. decreasing proportions of heroin-positive urine samples with increasing SROM doses). Retention in treatment showed no significant differences between treatments (period 1/period 2: SROM: 88.7%/82.1%, methadone: 91.1%/88.0%; period 1: P = 0.50, period 2: P = 0.19). Overall, safety outcomes were similar between the two groups.
  
  
  CONCLUSIONS
  Slow-release oral morphine appears to be at least as effective as methadone in treating people with opioid use disorder.
authors.affiliation: Arud Centres for Addiction Medicine, Zurich, Switzerland.
authors.forename: Thilo
authors.initials: T
authors.lastname: Beck
authors.forename: Christian
authors.initials: C
authors.lastname: Haasen
authors.forename: Uwe
authors.initials: U
authors.lastname: Verthein
authors.forename: Stephan
authors.initials: S
authors.lastname: Walcher
authors.forename: Christoph
authors.initials: C
authors.lastname: Schuler
authors.forename: Markus
authors.initials: M
authors.lastname: Backmund
authors.forename: Christian
authors.initials: C
authors.lastname: Ruckes
authors.forename: Jens
authors.initials: J
authors.lastname: Reimer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003061:Codeine / Q000031:analogs & derivatives / Q000652:urine; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D055118:Medication Adherence; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D009022:Morphine Derivatives / Q000652:urine; D009294:Narcotics / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment / Q000379:methods*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D009022:Morphine Derivatives; D009294:Narcotics; C053740:acetylcodeine; D009020:Morphine; C026979:6-O-monoacetylmorphine; D008691:Methadone; D003061:Codeine
keywords: Dose-response; maintenance treatment; methadone; opioid addiction; retention rate; slow-release oral morphine