Initiating buprenorphine to treat opioid use disorder without prerequisite withdrawal: a systematic review

Background: Opioid withdrawal symptoms prior to buprenorphine initiation may be intolerable and as a result, alternative strategies have emerged. We aim to systematically review the efficacy and safety of buprenorphine initiation that aims to omit prerequisite withdrawal. Methods: We conducted a systematic literature search of MEDLINE and CENTRAL from 1996 through April 10, 2020, augmented with searches in Google Scholar and . A study was included if it was in patients with substance use disorder or chronic pain that were taking a full mu opioid agonist and transitioning to buprenorphine without preceding withdrawal, and reported withdrawal during initiation as an outcome. Two investigators independently screened citations and articles for inclusion, collected data using a standardized data collection tool, and assessed study risk of bias. Results: We included 15 case reports/series, reporting 24 unique cases, in our qualitative synthesis. No controlled studies were identified. Microdosing and bridging with a buprenorphine patch were the most common strategies reported. Transition to buprenorphine with complete cessation of opioid agonists was achieved in 87.5% (n = 21) of cases. Withdrawal during initiation occurred in 58.3% (n = 14) of cases, two of which were at least moderate in severity. Conclusion: Buprenorphine initiation strategies that omit prerequisite withdrawal have emerged. Low quality evidence from case reports suggests withdrawal during initiation is common but most often mild in severity. There is an unmet need for controlled studies to inform their efficacy and safety compared with traditional strategies, including outcomes during initiation and in the long-term.