Variants of opioid genes and response to treatment of opioid use disorder with buprenorphine-naloxone versus extended-release naltrexone in Caucasians

Matthew Randesi, John Rotrosen, Edward V. Nunes, Joshua D. Lee, Patricia Novo, Orna Levran, Jurg Ott, Martina Pavlicova, Jennifer Scodes, Mary Jeanne Kreek

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sublingual buprenorphine-naloxone (BUP-NX), an FDA-approved treatment for opioid use disorder (OUD), combines buprenorphine (a partial mu/kappa agonist) with naloxone (a mu/ kappa antagonist). Extended-release injection naltrexone (XR-NTX; a mu receptor antagonist and kappa receptor partial agonist) is also an FDA-approved treatment for OUD. However, while some patients respond well to these medications, many others leave treatment and relapse. Objectives: Determine whether gene variants in the opioid gene system are associated with better or worse treatment response. Methods: In a 24-week, multisite, randomized, comparative effectiveness trial of daily, sublingual self-administration of BUP-NX versus monthly injection of XR-NTX conducted in the National Drug Abuse Clinical Trials Network, DNA was collected and four opioid gene variants were evaluated: (1) mu opioid receptor 118A>G; (2) 68-bp repeat in prodynorphin; (3) prodynorphin SNP rs910080; and (4) kappa opioid receptor SNP rs6473797. In non-Hispanic Caucasians (N = 334), two outcomes measures were assessed: received first dose (yes/no) and received last dose (yes/no). Separate logistic regressions were used to model each outcome measure as a function of treatment (XR-NTX vs BUP-NX), each gene variant, and their interaction. Results: There were no significant main effects of gene variant on receiving first dose or last dose. There were also no significant gene variant by treatment interactions. Conclusions: The outcome of treatment of OUD with medications is likely a complex function of multiple factors, including environmental, psychosocial, and possibly genetic, such that major effects of genetic variants may be unlikely.

Original languageEnglish (US)
Pages (from-to)761-768
Number of pages8
JournalAmerican Journal of Drug and Alcohol Abuse
Volume46
Issue number6
DOIs
StatePublished - 2020

Keywords

  • BUP-NX
  • opioid gene variants
  • response to treatment
  • xr-NTX

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Clinical Psychology
  • Psychiatry and Mental health

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