Association between methadone or buprenorphine use during medically supervised opioid withdrawal and extended-release injectable naltrexone induction failure

Abstract

Background: Extended-release naltrexone (XR-NTX) is an effective maintenance treatment for opioid use disorder, but induction from active opioid use is a challenge as individuals must complete detoxification before induction. We aimed to determine whether use of methadone or buprenorphine, long acting agonist opioids commonly used for detoxification, were associated with decreased likelihood of induction onto XR-NTX.

Methods: We performed a secondary analysis of a large open-label randomized trial of buprenorphine versus XR-NTX for treatment of individuals with opioid use disorder recruited from eight short term residential (detoxification) units. This analysis only included individuals randomized to the XR-NTX arm of the trial (N = 283). The method of detoxification varied according to usual practices at each inpatient program. Logistic regression models estimating the log-odds of induction onto XR-NTX were fit, with detoxification regimen received as the predictor.

Results: In the unadjusted logistic regression model, detoxification drug received (either methadone or buprenorphine) was significantly associated with decreased likelihood of induction onto XR-NTX compared to receiving non-opioid detoxification (Overall: P < 0.001); buprenorphine vs non-opioid detoxification: OR (95% CI) = 0.32 (0.15-0.67); methadone vs non-opioid detoxification: OR (95% CI) = 0.23 (0.11-0.46). After controlling for site as a random effect, the association of detoxification drug with induction success lost statistical significance.

Conclusions: Use of agonist medication during detoxification was associated with XR-NTX induction failure. Medication choice was determined by each site's clinical practice and therefore this association could not be separated from other site level variables.

Clinical trial registration: NCT02032433.

Keywords: Buprenorphine; Methadone; Naltrexone; Opioid use disorder; Pain.

Conflict of interest statement

Disclosures/ Conflict of Interest: Dr. Nunes has received medication for research studies from Alkermes/Cephalon, Duramed Pharmaceuticals, and Reckitt-Benckiser. Dr. Rotrosen reports medication for the present study from Indivior, and medication and/or funds for other studies (as principle investigator or investigator) from Indivior and Alkermes. The remaining authors have no conflicts of interest to report.

Copyright © 2021 Elsevier Inc. All rights reserved.

Figures

Figure 1:

Percent XR-NTX Induction by Medication