Prospects for a Genomic Approach to the Treatment of Alcoholism

O’Brien, Charles P.

doi:10.1001/archgenpsychiatry.2007.32

Cited by 14 publications

(13 citation statements)

References 16 publications

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“…These findings have been met with considerable enthusiasm as well as a healthy level of skepticism. As stated by O’Brien (2008), if supported, “the results of such pharmacogenetic studies could change clinical practice so that the selection of medication could be based on genotype rather than guesswork” (p. 133). Personalized medicine is the ultimate goal of pharmacogenetic studies, and the field of alcoholism has received attention for its strong efforts toward personalized care (Kranzler and Edenberg, 2010; Kuehn, 2009).…”

Section: Pharmacogenetic Studies and Clinical Trialsmentioning

confidence: 99%

The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review

Ray

Barr

Blendy

et al. 2011

Alcoholism Clin & Exp Res

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The endogenous opioid system has been implicated in the pathophysiology of alcoholism as it modulates the neurobehavioral effects of alcohol. A variant in the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received attention as a functional variant that may influence a host of behavioral phenotypes for alcoholism as well as clinical response to opioid antagonists. This paper will review converging lines of evidence on the effect of the Asn40Asp SNP on alcoholism phenotypes, including: (i) genetic association studies; (ii) behavioral studies of alcoholism; (iii) neuroimaging studies; (iv) pharmacogenetic studies and clinical trials; and (v) preclinical animal studies. Together, these lines of research seek to elucidate the effects of this functional polymorphism on alcoholism etiology and treatment response.

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Section: Pharmacogenetic Studies and Clinical Trialsmentioning

confidence: 99%

The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review

Ray

Barr

Blendy

et al. 2011

Alcoholism Clin & Exp Res

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“…Increased knowledge about genetic moderators of medication response can be applied to treatment decision-making including dosing algorithms based on genetically-determined differences in drug metabolism (Kirchheiner et al, 2004; O'Brien, 2008). Both pharmacokinetic and pharmacodynamic genes are thought to influence medication response.…”

Section: Introductionmentioning

confidence: 99%

A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers.

Ray

Miranda²,

MacKillop

et al. 2009

Experimental and Clinical Psychopharmacology

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Topiramate, an anticonvulsant medication, is an efficacious treatment for alcohol dependence. To date, little is known about genetic moderators of side effects from topiramate. The objective of this study was to examine three single nucleotide polymorphisms (SNPs) of the glutamate receptor GluR5 gene (GRIK1) as predictors of topiramate-induced side effects in the context of a laboratory study of topiramate. Heavy drinkers (n = 51, 19 females), 75% of whom met criteria for an alcohol use disorder, completed a 5-week dose escalation schedule to a target dose of either 200 or 300 mg, or matched placebo. The combined medication groups were compared to placebo-treated individuals for side effects at target dose. Analyses revealed that a SNP in intron 9 of the GRIK1 gene (rs2832407) was associated with the severity of topiramate-induced side effects and with serum levels of topiramate. Genes underlying glutamatergic neurotransmission, such as the GRIK1 gene, may help predict heterogeneity in topiramate-induced side effects. Future studies in larger samples are needed to more fully establish these preliminary findings.

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“…Currently the Center is engaged in a prospective study of depot naltrexone in the treatment of alcoholism with patients genotyped in advanced and randomized so that equal numbers of the SNP under study and those with the standard allele are in medication and placebo groups. If our hypothesis is again supported by the data, we will have evidence for genomic data to be used in the selection of medication for this disorder (O'Brien, 2008).…”

Section: Treatment Of Opioid Addictionmentioning

confidence: 74%