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Moderation of baclofen response by a GABA B receptor polymorphism: results from the BacALD randomized controlled trial
Author(s) -
Morley Kirsten C.,
Luquin Natasha,
Baillie Andrew,
Fraser Isabel,
Trent Ronald J.,
Dore Glenys,
Phung Nghi,
Haber Paul S.
Publication year - 2018
Publication title -
addiction
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.424
H-Index - 193
eISSN - 1360-0443
pISSN - 0965-2140
DOI - 10.1111/add.14373
Subject(s) - baclofen , abstinence , craving , placebo , confidence interval , randomized controlled trial , hazard ratio , medicine , alcohol dependence , alcohol use disorder , alcohol , anesthesia , psychiatry , addiction , receptor , biology , agonist , biochemistry , alternative medicine , pathology
Abstract Background and Aims Baclofen has been shown to reduce alcohol consumption in alcohol‐dependent individuals, but there is marked heterogeneity in response. An association between GABBR1 rs29220 and alcohol dependence has been demonstrated previously. The present study evaluated whether the response to baclofen is moderated by a single nucleotide polymorphism (rs29220) in the GABAB receptor subunit 1 gene (GABBR1). Design Double‐blind, placebo‐controlled study. Setting Australia. Participants Seventy‐two alcohol‐dependent men and women receiving 12 weeks of 30 mg/day of baclofen, 75 mg baclofen or placebo. Measurements Primary outcomes included time to lapse (any drinking) and relapse (> 5 drinks per day in men and > 4 in women). We also examined alcohol consumption at follow‐up (drinks per drinking day, number of heavy drinking days and percentage days abstinent). Findings We observed significant medication × genotype interaction effect for time to relapse ( P = 0.049) and a near‐significant interaction effect for time to lapse ( P = 0.055). For the CC genotype group, the relapse hazard ratio for baclofen versus placebo was 0.32 [95% confidence interval (CI) = 0.14–0.75] and for the G– group it was 1.07 (95% CI = 0.43–2.63). There was also a significant medication × genotype interaction for follow‐up alcohol consumption (drinks per drinking day, heavy drinking days and days abstinent) ( P = 0.02). Covarying for baseline levels of craving, aspartate aminotransferase and abstinence before enrolment reduced the medication × genotype effect for time to lapse and relapse but not for alcohol consumption at follow‐up. Conclusions The GABBR1 rs29220 polymorphism may influence treatment response and possibly predict adverse effects to baclofen in the treatment of alcohol dependence.