TY - JOUR
T1 - Variants of opioid genes and response to treatment of opioid use disorder with buprenorphine-naloxone versus extended-release naltrexone in Caucasians
AU - Randesi, Matthew
AU - Rotrosen, John
AU - Nunes, Edward V.
AU - Lee, Joshua D.
AU - Novo, Patricia
AU - Levran, Orna
AU - Ott, Jurg
AU - Pavlicova, Martina
AU - Scodes, Jennifer
AU - Kreek, Mary Jeanne
N1 - Funding Information:
Supported by the National Institute on Drug Abuse (NIDA) through a collaborative clinical trial mechanism, PAR-07-232 (R01DA024554, to Dr. Nunes; and R01DA024555, to Dr. Lee), and additional support (K24DA022412, to Dr. Nunes). Trial medication was provided in kind from an investigator-initiated grant from Alkermes. Dr. Lee reports receiving grant support and study medication from Alkermes and study medication from Indivior (formerly Reckitt Benckiser). Dr. Nunes reports serving on an advisory board for Alkermes, receiving study medication from Reckitt Benckiser and Duramed Pharmaceuticals, being lead investigator for a NIDA-funded study of a computer-delivered behavioral intervention supplied by HealthSim, and being site principal investigator for a study funded by, and receiving travel support from, Brainsway. Dr. Rotrosen reports study support in his role as PI or Investigator in the form of funds or donated medication from Alkermes (manufacturer of Vivitrol) and from Indivior (manufacturer of Suboxone) and serves as a nonpaid member of an Alkermes study steering committee. Indivior donated Suboxone for the present study. No paid consulting, speaker or other activities, no equity. No other potential conflict of interest relevant to this article was reported;Dr. Miriam and Sheldon G. Adelson Medical Research Foundation;National Institute on Drug Abuse (NIDA) [R01DA024554 and K24DA022412 (Dr. Nunes); R01DA024555 (Dr. Lee)].
Publisher Copyright:
© 2020 Taylor & Francis Group, LLC.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - BUP-NX
KW - opioid gene variants
KW - response to treatment
KW - xr-NTX
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U2 - 10.1080/00952990.2020.1797064
DO - 10.1080/00952990.2020.1797064
M3 - Article
C2 - 32851876
AN - SCOPUS:85089911224
SN - 0095-2990
VL - 46
SP - 761
EP - 768
JO - American Journal of Drug and Alcohol Abuse
JF - American Journal of Drug and Alcohol Abuse
IS - 6
ER -