Table 1
Characteristics of included studies
| Study/ Country | Design | Participants | Interventions | Outcomes | Risk rating |
| Clark et al28 Australia | Crossover Randomised controlled trial (RCT) Open-label; Duration: 12 weeks | n=11 Mean age: 36.5 years Use of heroin: once per week Heroin use disorder and were on methadone | (1) Morphine Flexible starting dose increased by 50 mg per day following transfer, never exceeded 800 mg/day (2) Methadone Flexible starting dose reduced by 12 mg per day following transfer | Retention Severity of opiate withdrawal symptoms Heroin or other substance use Severity of dependence Mental health/social functioning |  |
| Eder et al26 Austria | Crossover Randomised double blind, double-dummy; Duration: 14 weeks | n=64 Mean age: 28 years Male: 75% Opioid use disorder (OUD) (excluded patients already receiving maintenance therapy) | (1) Morphine Starting dose 200 mg/day increased to 800 mg/day by week 1 (2) Methadone Starting dose 40 mg/day increased to 100 mg/day by week 1 | Retention Use of illicit substances based on urinalysis Extent of drug cravings Withdrawal symptoms General well-being Safety was assessed on the basis of adverse events and clinical and physical examination Quality of life (QoL) measured by the Lancashire Quality of Life Profile |  |
| Giacomuzzi et al27 Austria | RCT Open-label; Duration: 24 weeks | n=120 Mean age: 27 years; Male: 57% OUD and were on methadone | (1) Morphine; maintenance dose dependent on severity of withdrawal symptoms (2) Methadone; maintenance dose dependent on severity of withdrawal symptoms (3) Buprenorphine; maintenance dose dependent on severity of withdrawal symptoms | Retention (from personal correspondence) QoL measured by the Lancashire Quality of Life Profile Withdrawal symptoms measured by the Opioid Withdrawal Scale |  |
| Beck et al17 Switzerland and Germany | Crossover RCT Open-label Duration: 22 weeks | n=276 Mean age: 38.1 Male: 81.5% Opioid dependence and were on methadone | (1) Methadone; Flexible dosing Crossover at 11 weeks to morphine (2) Morphine; Flexible dosing Crossover at 11 weeks to methadone | Retention (24 weeks) Proportion of positive urine samples per patient (12 weeks) Per treatment for co-consumption of heroin Craving heroin Craving cocaine Self-reported drug use Mental health problems (SCL-27) Positive urine samples Adverse events |  |
Risk rating legend:
A—random sequence generation (selection bias); amber circle: unclear; B—allocation concealment (selection bias); C—blinding of participants and personnel (performance bias); D—blinding of outcome assessment (detection bias); E—incomplete outcome data (attrition bias).