Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone

ABSTRACT

Background

Pharmacologic treatment is recommended for many individuals with opioid use disorder (OUD). For patients who select opioid antagonist treatment, effective management of opioid withdrawal symptoms during transition to antagonist treatment requires consideration of the patient experience.

Objectives

To compare patterns of opioid withdrawal between those withdrawing from untreated opioid use and those withdrawing from buprenorphine.

Methods

We performed a post hoc, cross-study comparison of the temporal pattern of opioid withdrawal during 1-week induction onto extended-release naltrexone by similar protocols enrolling two participant populations: participants with OUD entering a study with untreated opioid use (N = 378, NCT02537574) or on stable buprenorphine (BUP) treatment (N = 101, NCT02696434).

Results

The temporal pattern of withdrawal from induction day 1 through day 7 differed between the two participant populations for Clinical Opiate Withdrawal Score (COWS) and Subjective Opiate Withdrawal Score (SOWS): participants with untreated OUD prior to study entry were more likely to experience an earlier relative peak in opioid withdrawal followed by a gradual decline, whereas participants on stable BUP treatment prior to study entry were more likely to experience a relatively later, though still mild, peak opioid withdrawal. The peak COWS was reached at a mean (standard deviation) of 1.9 (1.5) days for participants with untreated OUD and 5.0 (1.5) days for participants on stable BUP. Daily peak cravings were generally higher for participants with untreated OUD than participants on stable BUP.

Conclusion

Awareness of population-specific variations in the patient experience of opioid withdrawal may help clinicians anticipate the expected course of withdrawal.

KEYWORDS:

• Antagonist
• maintenance
• opioid discontinuation
• partial agonist
• substance use

Acknowledgements

Medical writing support was provided by Janelle Keys, PhD, CMPP, of ProScribe – Envision Pharma Group, and was funded by Alkermes, Inc.

Credit author statement

All authors participated in the interpretation of study results and in the drafting, critical revision, and approval of the final version of the manuscript. PM and ABD were study investigators; SCA, AZ, MAS, and AL were involved in the study design and data analyses. AL conducted the statistical analyses.

Data availability statement

The data collected in this study are proprietary to Alkermes, Inc. Alkermes, Inc. is committed to public sharing of data in accordance with applicable regulations and laws.

Disclosure statement

PM has received consultation fees and grants from Alkermes, Inc. and other pharmaceutical companies. ABD has participated in advisory boards and received grants from Alkermes, Inc. SCA and MAS are employees and shareholders of Alkermes, Inc. AZ and AL are former employees of Alkermes, Inc., and may own stock or options in the company. MAS previously received study medication from Alkermes, Inc. for a NIDA-funded investigation.

Role of the funding source

Alkermes, Inc. was involved in the study design, data collection, data analysis, and preparation of the manuscript.

Additional information

Funding

This study was sponsored by Alkermes, Inc., the manufacturer/licensee of XR-NTX.