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Pharmacogenetics of alcohol and alcohol dependence treatment.

ABSTRACT: In this article, we review studies of genetic moderators of the response to medications to treat alcohol dependence, the acute response to alcohol, and the response to the psychotherapeutic treatment of heavy drinking. We consider four neurotransmitter systems: opioidergic, dopaminergic, GABAergic, and glutamatergic and focus on one receptor protein in each: OPRM1 (the &#micro;-opioid receptor gene), DRD4 (the D(4) dopamine receptor gene), GABRA2 (GABA(A) receptor alpha-2 subunit gene), and GRIK1 (the kainite receptor GluR5 subunit gene). We conclude that because parallel developments in alcoholism treatment and the genetics of alcohol dependence are beginning to converge, using genotypic information, it may be possible to match patients with specific treatments. Of greatest clinical relevance is the finding that the presence of an Asp40 allele in OPRM1 modestly predicts a better response to naltrexone treatment. Promising findings include the observations that a polymorphism in GABRA2 predicts the response to specific psychotherapies; a polymorphism in DRD4 predicts the effects of the antipsychotic olanzapine on craving for alcohol and drinking behavior; and a polymorphism in GRIKI predicts adverse events resulting from treatment with the anticonvulsant topiramate. Although variants in other genes have been associated with the risk for alcohol dependence, they have not been studied as moderators of the response either to treatment or acute alcohol administration. We recommend that, whenever possible, treatment trials include the collection of DNA samples to permit pharmacogenetic analyses, and that such analyses look broadly for relevant genetic variation.

SUBMITTER: Kranzler HR

PROVIDER: S-EPMC4142701 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Pharmacogenetics of alcohol and alcohol dependence treatment.

Kranzler Henry R HR Edenberg Howard J HJ

Current pharmaceutical design 20100101 19

In this article, we review studies of genetic moderators of the response to medications to treat alcohol dependence, the acute response to alcohol, and the response to the psychotherapeutic treatment of heavy drinking. We consider four neurotransmitter systems: opioidergic, dopaminergic, GABAergic, and glutamatergic and focus on one receptor protein in each: OPRM1 (the &#micro;-opioid receptor gene), DRD4 (the D(4) dopamine receptor gene), GABRA2 (GABA(A) receptor alpha-2 subunit gene), and GRIK ...[more]

PMID: 20482509

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Project description:BackgroundThe tradition of consuming alcohol has long been a part of Italian culture and is responsible for a large health burden. This burden may be reduced with effective interventions, one of the more important of which is treatment for Alcohol Dependence (AD). The aim of this article is to estimate the burden of disease in Italy attributable to alcohol consumption, heavy alcohol consumption, and AD. An additional aim of this paper is to examine the effects of increasing the coverage of treatment for AD on the alcohol-attributable burden of disease.MethodsAlcohol-attributable deaths and the effects of treatments for AD were estimated using alcohol-attributable fractions and simulations. Deaths, potential years of life lost, years lived with disability, and disability adjusted life years lost were obtained for 2004 for Italy and for the European Union from the Global Burden of Disease study. Alcohol consumption data were obtained from the Global Information System on Alcohol and Health. The prevalences of current drinkers, former drinkers, and lifetime abstainers were obtained from the GENder Alcohol and Culture International Study. The prevalence of AD was obtained from the World Mental Health Survey. Alcohol relative risks were obtained from various meta-analyses.Results5,320 deaths (1,530 female deaths; 3,790 male deaths) or 5.9% of all deaths (4.9% of all female deaths; 6.3% of all male deaths) of people 15 to 64 years of age were estimated to be alcohol-attributable. Of these deaths, 74.5% (61.3% for females; 79.8% for males) were attributable to heavy drinking, and 26.9% (25.6% for females; 27.5% for males) were attributable to AD. Increasing pharmacological AD treatment coverage to 40% would result in an estimated reduction of 3.3% (50 deaths/year) of all female and 7.6% (287 deaths/year) of all male alcohol-attributable deaths.ConclusionsAlcohol was responsible for a large proportion of the burden of disease in Italy in 2004. Increasing treatment coverage for AD in Italy could reduce that country's alcohol-attributable burden of disease.

Project description:Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics.To determine if gabapentin, a widely prescribed generic calcium channel/?-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner.A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital.Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling.Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study. RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups.Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence.clinicaltrials.gov Identifier: NCT00391716.

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Pharmacogenetics of alcohol and alcohol dependence treatment.

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Pharmacogenetics of alcohol and alcohol dependence treatment.

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