title: Pharmacogenetic approaches in the treatment of alcohol use disorders: addressing clinical utility and implementation thresholds.
abstract: Despite advances in characterizing genetic influences on addiction liability and treatment response, clinical applications of these efforts have been slow to evolve. Although challenges to clinical translation remain, stakeholders already face decisions about evidentiary thresholds for the uptake of pharmacogenetic tests in practice. There is optimism about potential pharmacogenetic applications for the treatment of alcohol use disorders, with particular interest in the OPRM1 A118G polymorphism as a moderator of naltrexone response. Findings from human and animal studies suggest preliminary evidence for the clinical validity of this association; on this basis, arguments for clinical implementation can be made in accordance with existing frameworks for the uptake of genomic applications. However, generating evidence-based guidelines requires evaluating the clinical utility of pharmacogenetic tests. This goal will remain challenging, largely due to minimal data to inform clinical utility estimates. The pace of genomic discovery highlights the need for clinical utility and implementation research to inform future translation efforts. Near-term implementation of promising pharmacogenetic tests can help expedite this goal, generating an evidence base to enable efficient translation as additional gene-drug associations are discovered.
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. christian.hendershot@utoronto.ca.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Hendershot
mesh_terms: D019973:Alcohol-Related Disorders / Q000188:drug therapy* / Q000235:genetics*; D019317:Evidence-Based Medicine; D005838:Genotype; D006801:Humans; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D017450:Receptors, Opioid, mu / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009271:Naltrexone