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

Abstract

AimsTo compare the efficacy of slow-release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone.DesignProspective, 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.SettingFourteen out-patient addiction treatment centres in Switzerland and Germany.ParticipantsAdults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks.MeasurementsThe 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%.FindingsOne 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.ConclusionsSlow-release oral morphine appears to be at least as effective as methadone in treating people with opioid use disorder.

Mental Symptoms and Drug Use in Maintenance Treatment with Slow-Release Oral Morphine Compared to Methadone: Results of a Randomized Crossover Study

“…For study inclusion, patients had to be opioid dependent (F11.2 according to ICD-10), aged 18 years or older and already participating in methadone maintenance treatment for at least 26 weeks. The study design is described in detail elsewhere [see [8]]. The main part of the study comprised two crossover periods of 11 weeks each (1 week adjustment phase followed by 10 weeks of treatment; see fig.…”

“…To increase the validity of the study results, stringent criteria for the per protocol (PP) population were set to include patients who completed each of the two crossover treatment periods (11 weeks) within a specified time frame of ≥70 days and ≤84 days, who had urinalyses for ≥9 out of 11 weeks per crossover period and no discontinuation of study medication for more than 5 consecutive days [see [8]].…”

“…In several studies, slow-release oral morphine has been proven as an efficacious medication for reduction of illicit drug use, with effects similar to methadone maintenance treatment [3,8,9,10]. Given the high prevalence rates of psychiatric comorbidity in opioid-dependent patients, the effects of substitution medication on these symptoms in particular are of special interest [11].…”

“…A recent crossover trial confirmed the noninferiority of slow-release oral morphine regarding the additional use of heroin compared to methadone [8]. This report focuses on the results of patient-reported outcomes from the study, which were secondary efficacy-related parameters.…”

Management of opioid use disorders: a national clinical practice guideline

“…59 Since this review, an international multisite randomized cross-over trial found that slow-release oral morphine was as effective as methadone in reducing illicit opioid use and retaining individuals in treatment, 60 and superior to methadone for overall patient satisfaction, and reducing cravings and symptoms of dysthymia. [61][62][63] However, because of the small number of trials comparing slowrelease oral morphine to other opioid agonist treatments, slowrelease oral morphine should generally be considered only for use in patients who are intolerant to or have not responded to first-and second-line opioid agonist treatment, and who remain at high risk of opioid-related harms, including overdose death.…”