Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone

• Published in: Addiction (Abingdon, England) Vol. 109; no. 4; pp. 617 - 626
• Main Authors: Beck, Thilo, Haasen, Christian, Verthein, Uwe, Walcher, Stephan, Schuler, Christoph, Backmund, Markus, Ruckes, Christian, Reimer, Jens
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-04-2014; Blackwell; BlackWell Publishing Ltd
• Subjects: Addictive behaviors; Administration, Oral; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Codeine - analogs & derivatives; Codeine - urine; Cross-Over Studies; Delayed-Action Preparations; Dose-response; Drug addiction; Female; Humans; Maintenance Chemotherapy; maintenance treatment; Male; Medical sciences; Medication Adherence; Methadone; Methadone - therapeutic use; Middle Aged; Morphine - therapeutic use; Morphine Derivatives - urine; Narcotics; Narcotics - therapeutic use; Opiate Substitution Treatment - methods; opioid addiction; Opioid-Related Disorders - drug therapy; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Research Reports; retention rate; slow-release oral morphine; Substance abuse treatment; Treatment Outcome; Switzerland; Germany; slow-release oral morphine; Morphine; Opiates; Methadone; Narcotic analgesic; Retention; Dose activity relation; Randomization; Maintenance treatment; Dependence; Clinical trial; Dose-response; Drug of abuse; Release; opioid addiction; Human; Narcotic antagonist; Drug addiction; Rate; Oral administration; Non -inferiority study; Crossover study; Addiction; Comparative study; retention rate; methadone; maintenance treatment
• ISSN: 0965-2140; 1360-0443
• DOI: 10.1111/add.12440

Aims
To compare the efficacy of slow‐release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone.
Design
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.
Setting
Fourteen out‐patient addiction treatment centres in Switzerland and Germany.
Participants
Adults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks.
Measurements
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%.
Findings
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.