Outpatient Direct Initiation of Injectable Buprenorphine From Methadone: A Case Series

Published protocols for directly initiating injectable buprenorphine from full opioid agonists ("direct-to-inject" or DTI) have largely described patients with active or recent fentanyl use. Among patients with opioid use disorder (OUD) in remission, transitioning from methadone to buprenorphine with sublingual buprenorphine can be challenging. Published experience utilizing DTI buprenorphine from methadone is limited.

In this retrospective cohort study, we identified 15 patients across an academic hospital system who reported OUD in remission, were engaged in methadone treatment, and requested an outpatient DTI buprenorphine transition in 2025. Individuals who took ≥4 mg sublingual buprenorphine within the preceding 24 hours were excluded. All participants were offered consent and elected for DTI buprenorphine after counseling on risks, benefits, and alternatives. Primary outcome was receipt of one monthly formulation of injectable buprenorphine. Demographics, protocol completion, and 90-day retention on buprenorphine were reviewed. Patients retrospectively rated their transition-related discomfort on the following scale: no, mild, moderate, or severe discomfort.

Mean methadone dose was 71.5 mg (range: 24-120). Median length of methadone treatment episode was 2 years (range: 2 mo-10 y). Completion of one monthly extended-release buprenorphine injection was 93%. One-third (33%) reported moderate or severe discomfort with the protocol, with symptoms responsive to anxiolytics. All participants reporting moderate-to-severe discomfort had methadone doses ≥95 mg. Ninety-day buprenorphine retention was 67%, with most unretained patients utilizing injectable buprenorphine to taper off medication for OUD.

DTI buprenorphine with weekly injectable buprenorphine was a feasible and generally well-tolerated approach for transitioning patients from methadone to buprenorphine.