Methadone-Buprenorphine Transfers Using Low Dosing of Buprenorphine: An Open-label, Nonrandomized Clinical Trial

To compare a low-dosing protocol to standard practice for methadone-buprenorphine transfers.

We undertook a nonrandomized open-label clinical trial across 8 sites from NSW, Australia. Participants prescribed methadone wishing to transfer to buprenorphine could either choose or be randomized to a low-dose transfer or standard care transfer as per NSW health guidelines. The low-dose protocol started at 0.2 mg BD and increased to 16 mg on day 6, with flexible dosing thereafter. The primary outcome was continuation of buprenorphine 1 week post-transfer. Binary logistic regression was used to access the primary outcome with demographic differences between the groups included as covariates.

There were 117 participants who commenced the study, 101 in the low-dose arm and 16 in standard care. Mean methadone dose was 82 mg in the low-dose arm and 46 mg in standard care. The primary outcome was met by 81 participants in the low-dose arm (80%) and 13 participants in standard care (81%). There was no significant between-arm difference in the odds of the primary outcome (OR = 2.22; 95% CI: 0.45-10.91; P = 0.327). Four participants (4%) in the low-dose arm experienced precipitated withdrawal against 1 (6%) in standard care. Higher methadone dose decreased the odds of successful transfer by 20% (OR = 0.8 per 10 mg methadone; 95% CI: 0.7-0.99; P = 0.04). Withdrawal scores between the 2 arms were similar.

We were unable to detect a difference between low dosing and standard care for methadone to buprenorphine transfers. Increasing methadone dose was a predictor of success; setting (ambulatory or inpatient) was not.