Cognitive performance of patients with opioid use disorder transitioned to extended-release injectable naltrexone from buprenorphine: Post hoc analysis of exploratory results of a phase 3 randomized controlled trial

Abstract

Background: Opioid use disorder (OUD) is associated with cognitive dysfunction. Understanding how pharmacotherapy may affect cognition is an important treatment consideration.

Methods: This was a hybrid residential-outpatient, randomized trial assessing transition regimens (naltrexone/buprenorphine [NTX/BUP] vs placebo-NTX/buprenorphine [PBO-N]/BUP) to extended-release naltrexone (XR-NTX) in patients with OUD seeking BUP discontinuation. Cognition was assessed at baseline, Day 22 (XR-NTX Day 14), and Day 36 (XR-NTX Day 28) using a range of measures (Brief Assessment of Cognition Symbol Coding test, Controlled Oral Word Association Task, Wechsler Memory Scale-III Spatial Span test, Continuous Performance Test, and Test of Attentional Performance). Pre-specified exploratory analyses compared treatment groups. Post hoc analyses were treatment-arm-independent analyses overall and by baseline BUP dose (<8 mg/day [low-dose] or 8 mg/day [higher-dose]).

Results: Baseline cognitive measures were similar between NTX/BUP and PBO-N/BUP groups and between BUP low-dose and higher-dose groups. There were improvements in several cognitive outcomes at Day 22 and Day 36 relative to baseline for the overall population, but no differences between NTX/BUP and PBO-N/BUP treatment groups were observed. Participants entering the study on low-dose BUP showed improvements at Day 36 relative to baseline in 5 of 7 cognitive outcomes; participants entering the study on higher-dose BUP generally did not show improvements in cognitive outcomes.

Conclusions: Improvements in most cognitive domains were associated with the transition from BUP to XR-NTX, particularly in participants entering the study on low-dose (<8 mg/day) BUP. These improvements may be due to the discontinuation of BUP, the treatment with XR-NTX, or both.

Trial registration: ClinicalTrials.gov NCT02696434.

Keywords: Buprenorphine; Cognition; Cognitive performance; Extended-release injectable naltrexone.

Conflict of interest statement

Declaration of competing interest Abigail Zavod, Sarah C. Akerman, and Maria A. Sullivan are employees and shareholders of Alkermes, Inc. Maria A. Sullivan previously received study medication from Alkermes for a NIDA-funded investigation. Narinder Nangia and Maria Lopez-Bresnahan are former employees of Alkermes, Inc. Thomas Kosten is a consultant and investigator for Alkermes, Inc. He is also supported by Indivior, Astellas, BioXcel, Embera, Opiant, Novartis, Otsuka, and US World Medsand. Efrat Aharonovich is a consultant for Alkermes, Inc.

Copyright © 2020 Alkermes, Inc. Published by Elsevier Ltd.. All rights reserved.