A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder

Autor: Anne Le Moigne, Richard C. Crist, Emily E. Hartwell, Anne C Andorn, Kevin G. Lynch, Celine M Laffont, Henry R. Kranzler
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Adult
Male
Narcotics
medicine.medical_specialty
AcademicSubjects/MED00415
Population
Placebo
Gastroenterology
Polymorphism
Single Nucleotide
White People
03 medical and health sciences
0302 clinical medicine
Double-Blind Method
Internal medicine
Receptors
Opioid
delta
medicine
Humans
Pharmacology (medical)
030212 general & internal medicine
education
Prospective cohort study
Regular Research Article
Pharmacology
education.field_of_study
business.industry
AcademicSubjects/SCI01870
Therapeutic effect
Opioid use disorder
opioid use disorder
Odds ratio
Middle Aged
medicine.disease
Opioid-Related Disorders
Buprenorphine
Pharmacogenomic Testing
Black or African American
Psychiatry and Mental health
Editor's Choice
Delayed-Action Preparations
pharmacogenetic
Female
delta-opioid receptor
rs678849
business
030217 neurology & neurosurgery
Pharmacogenetics
medicine.drug
Zdroj: International Journal of Neuropsychopharmacology
ISSN: 1469-5111
1461-1457
Popis: Background Buprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine. Methods We examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS). Results Among AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ 2(1) = 4.33, P = .04). Conclusion We found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.
Databáze: OpenAIRE
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