Factors That Distinguish Opioid Withdrawal During Induction with Buprenorphine Microdosing: a Configurational Analysis

Background: Novel buprenorphine dosing strategies have emerged with an aim to transition patients from opioid agonists to buprenorphine without prerequisite opioid withdrawal. We applied a configurational approach to a subset of data from our earlier systematic review to answer the following question: when patients received a buprenorphine initiation strategy aimed to eliminate prerequisite withdrawal, what factors consistently distinguished patients that experienced withdrawal during the initiation process from patients that did not?

Methods: From the 24 cases identified by our systematic review, we included cases that were treated using buprenorphine microdosing strategies (oral or transdermal), cases with opioid use disorder, and cases that fully transitioned to buprenorphine without continuing the full opioid agonist. Configurational analysis was used to identify combinations of patient and regimen level factors that uniquely distinguished cases experiencing withdrawal during induction.

Result: Fourteen cases were included in our analysis, of which 9 experienced opioid withdrawal symptoms. Three factors were involved in explaining both the presence and absence of withdrawal symptoms: history of heroin use, history of methadone use, and duration of overlap between buprenorphine and the full opioid agonist during induction. For the presence of withdrawal symptoms, the addition of a fourth factor "buprenorphine starting dose" resulted in a model with perfect consistency and coverage; for the absence of withdrawal symptoms, the addition of a fourth factor "induction duration" similarly resulted in a model with perfect consistency and 80% coverage.

Conclusion: Application of configurational methods allowed synthesis of case reports identified through a systematic review.