Effect modification in therapeutic impact of nalmefene on alcohol dependence by ADH1B polymorphism: A secondary analysis of a Japanese randomized clinical trial.
Background and Aims: The association between alcohol‐metabolizing enzyme polymorphisms and treatment response to nalmefene for alcohol dependence has not been studied. We aimed to determine whether alcohol‐metabolizing enzyme polymorphisms, specifically ADH1B rs1229984 and ALDH2 rs671, modify the tr...
| Publicado en: | Addiction Vol. 120; no. 12; pp. 2423 - 2435 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=189104080&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 189104080 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09652140 AIO jtl: Addiction issn: 09652140 maglogo: Y pubinfo: dt: Dec2025 vid: 120 iid: 12 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 189104080 187229003 189104080 189104080 10.1111/add.70160 189104080 ppf: 2423 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Effect modification in therapeutic impact of nalmefene on alcohol dependence by ADH1B polymorphism: A secondary analysis of a Japanese randomized clinical trial. aug: au: Hashimoto, Nozomu Takaki, Manabu Kojima, Yoshitsugu Nakamura, Izuru Ikeda, Daisuke D. Sakamoto, Shinji Okahisa, Yuko Takao, Soshi Matsuo, Keitaro affil: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Kita‐ku,, Japan sug: subj: Alcoholism Drug Therapy Alcoholism Familial and Genetic Naltrexone Therapeutic Use Narcotic Antagonists Therapeutic Use Polymorphism, Genetic Aldehyde Dehydrogenase Mitochondria Treatment Outcomes Human Male Female Adult Middle Age Japan Outpatient Service Randomized Controlled Trials Random Assignment Secondary Analysis Multicenter Studies Double-Blind Studies Placebos Pharmacogenetics Genetic Variation Genotype Dose-Response Relationship, Drug Chi Square Test Fisher's Exact Test Statistical Significance Data Analysis Software Descriptive Statistics Funding Source Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Background and Aims: The association between alcohol‐metabolizing enzyme polymorphisms and treatment response to nalmefene for alcohol dependence has not been studied. We aimed to determine whether alcohol‐metabolizing enzyme polymorphisms, specifically ADH1B rs1229984 and ALDH2 rs671, modify the treatment response to nalmefene for alcohol dependence. Design: Secondary analysis of a Japanese randomized clinical trial, in which participants were randomly assigned (4:3:4) to placebo, 10 mg nalmefene or 20 mg nalmefene groups for 24 weeks, accompanied by a brief psychosocial intervention. Setting: 80 addiction outpatient clinics across Japan. Participants: A subset of 531 individuals (mean age 49.2 years, standard deviation 11.5; 69.9% male), including 196 in the placebo group and 335 in the nalmefene group, who agreed to DNA preservation and had available DNA data between February 2015 and July 2016. Measurements: Genotyping was performed to determine ADH1B rs1229984 polymorphism (AA, AG, GG) and ALDH2 rs671 polymorphism (GG, GA, AA) in participants. Primary endpoint was change from baseline in monthly heavy drinking days (HDD, days/month) over the 24 treatment weeks. The key secondary endpoint was change from baseline in daily total alcohol consumption (TAC, g/day) over the 24 treatment weeks. Findings A mixed‐effects model for repeated measures analyses showed a statistically significant gene‐treatment interaction with ADH1B rs1229984 for TAC [10.71 (95% confidence interval = 4.03–17.39) g/day, P = 0.002], but not for HDD [1.65 (−0.38 to 3.67) days/month, P = 0.110]: as the G allele of rs1229984 increased, the efficacy regarding TAC decreased. In contrast, no statistically significant gene‐treatment interaction was seen with ALDH2 rs671 for either TAC [4.46 (−7.88 to 16.80) g/day, P = 0.478] or HDD [−0.91 (−4.60 to 2.78) days/month, P = 0.630]. In the ADH1B rs1229984 variant, the number needed to treat for two category shifts in drinking risk level, as defined by the World Health Organization, was 3.7 for AA carriers, 6.6 for AG carriers and 18.5 for GG carriers. Conclusions: The ADH1B rs1229984 polymorphism appears to moderate the response to nalmefene in Japanese patients with alcohol dependence. Specifically, nalmefene appears to show efficacy in individuals with the ADH1B rs1229984 AA genotype. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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