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

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.