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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.

SUBMITTER: Hendershot CS

PROVIDER: S-EPMC4165632 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Pharmacogenetic approaches in the treatment of alcohol use disorders: addressing clinical utility and implementation thresholds.

Hendershot Christian S CS

Addiction science & clinical practice 20140913 1

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 ...[more]

PMID: 25217046

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Project description:IntroductionAlcohol consumption is a leading global risk factor for ill-health and premature death. Alcohol screening and brief interventions (SBI) delivered in primary care is effective at reducing alcohol consumption, but routine implementation remains problematic. Screening all patients for excessive drinking (universal screening) is resource-intensive and may be at odds with general practitioners' (GPs') perceived professional role. This study aimed to develop a tailored, theory-based training intervention to strengthen GPs' ability to address alcohol and to manage alcohol-related health problems through a pragmatic approach based on clinical relevance.MethodsA qualitative study design involving focus group interviews and a structured questionnaire for free text replies with GPs in Norway. Behavioral analysis assessed factors influencing delivery of SBI according to the 'capability, opportunity, motivation and behavior' (COM-B) model to inform intervention development using the Behavior Change Wheel. Qualitative data were analyzed using framework analysis and an iterative approach was adopted to develop the training.ResultsA purposive sample of GPs attended the focus groups (n = 25) and completed the questionnaire (n = 55). Four areas required additional support including: understanding the link between alcohol use and health problems; opening up the conversation on alcohol use; addressing alcohol and dealing with obstacles; and following-up and maintaining change. Findings informed the development of a four-session interactive training intervention and a digital intervention for providing support for patients between consultations to address the identified needs.ConclusionThis work highlights the value of pragmatic, relevance-based clinical strategies, as opposed to universal screening approaches to addressing alcohol in primary care. A pragmatic approach is more in line with GPs existing sclinical skill set and holds the potential to improve widespread uptake and implementation of SBI in routine primary care.

Project description:Harmful alcohol use is responsible for a group of disorders collectively named alcohol use disorders (AUDs), according to the DSM-5 classification. The damage induced by alcohol depends on the amount, time, and consumption patterns (continuous and heavy episodic drinking). It affects individual global well-being and social and familial environments with variable impact. Alcohol addiction manifests with different degrees of organ and mental health detriment for the individual, exhibiting two main traits: compulsive drinking and negative emotional states occurring at withdrawal, frequently causing relapse episodes. Numerous individual and living conditions, including the concomitant use of other psychoactive substances, lie in the complexity of AUD. Ethanol and its metabolites directly impact the tissues and may cause local damage or alter the homeostasis of brain neurotransmission, immunity scaffolding, or cell repair biochemical pathways. Brain modulator and neurotransmitter-assembled neurocircuitries govern reward, reinforcement, social interaction, and consumption of alcohol behaviors in an intertwined manner. Experimental evidence supports the participation of neurotensin (NT) in preclinical models of alcohol addiction. For example, NT neurons in the central nucleus of the amygdala projecting to the parabrachial nucleus strengthen alcohol consumption and preference. In addition, the levels of NT in the frontal cortex were found to be lower in rats bred to prefer alcohol to water in a free alcohol-water choice compared to wild-type animals. NT receptors 1 and 2 seem to be involved in alcohol consumption and alcohol effects in several models of knockout mice. This review aims to present an updated picture of the role of NT systems in alcohol addiction and the possible use of nonpeptide ligands modulating the activity of the NT system, applied to experimental animal models of harmful drinking behavior mimicking alcohol addiction leading to health ruin in humans.

Dataset Information

Pharmacogenetic approaches in the treatment of alcohol use disorders: addressing clinical utility and implementation thresholds.

Publications

Pharmacogenetic approaches in the treatment of alcohol use disorders: addressing clinical utility and implementation thresholds.

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