AIMS: To test the hypothesis that switching from L-methadone to D,L-methadone is associated with more frequent withdrawal symptoms and side-effects than switching from D,L-methadone to L-methadone. DESIGN: Stratified, randomized 2 x 2 crossover study design over a time-period of 8 weeks. At study entry, every second patient was switched from the pre-study substance to the other medication, after 4 weeks all patients were subject to a (re-)switch. SETTING: The study was conducted as a multi-centre trial in three methadone maintenance therapy (MMT) clinics. PARTICIPANTS: Seventy-five patients previously treated with either D,L-methadone or L-methadone for at least 1 year took part in the study. MEASUREMENTS: Intra-individual changes in withdrawal symptoms (Short Opiate Withdrawal Scale, SOWS) and side-effects were defined as primary outcome criteria. Secondary outcome measures included necessity for methadone dose adjustment. FINDINGS: Complete data were available for 68 patients (91%). Sample strata were unbalanced at baseline: 15 patients (22%) were treated with L-methadone and 43 with D,L-methadone (78%). Thirty-five patients were randomized into the group treated with L-methadone and 33 into the group treated with D,L-methadone during the first 4 weeks. There were no significant differences in intra-individual change of withdrawal symptoms and side-effects between groups after crossover. However, patients treated with levomethadone tended to feel less withdrawal symptoms than patients treated with d,l-methadone. CONCLUSIONS: D,L-methadone and L-methadone can safely be replaced by each other on a 2:1 ratio. Withdrawal symptoms or side-effects due to conversion are of transient nature only.
