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Advances in Medications and Tailoring Treatment for Alcohol Use Disorder.

ABSTRACT: Alcohol use disorder (AUD) is a chronic heritable brain disorder with a variable clinical presentation. This variability, or heterogeneity, in clinical presentation suggests complex interactions between environmental and biological factors, resulting in several underlying pathophysiological mechanisms in the development and progression of AUD. Classifying AUD into subgroups of common clinical or pathological characteristics would ease the complexity of teasing apart underlying molecular mechanisms. Genetic association analyses have revealed several polymorphisms-small differences in DNA-that increase a person's vulnerability to develop AUD and other alcohol-related intermediate characteristics, such as severity of drinking, age of AUD onset, or measures of craving. They also have identified polymorphisms associated with reduced drinking. Researchers have begun utilizing these genetic polymorphisms to identify alcoholics who might respond best to various treatments, thereby enhancing the effectiveness of currently tested medications for treating AUD. This review compares the efficacy of medications tested for treatment of AUD with and without incorporating genetics. It then discusses advances in pre-clinical genetic and genomic studies that potentially could be adapted to clinical trials to improve treatment efficacy. Although a pharmacogenetic approach is promising, it is relatively new and will need to overcome many challenges, including inadequate scientific knowledge and social and logistic constraints, to be utilized in clinical practice.

SUBMITTER: Seneviratne C

PROVIDER: S-EPMC4476601 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Advances in Medications and Tailoring Treatment for Alcohol Use Disorder.

Seneviratne Chamindi C Johnson Bankole A BA

Alcohol research : current reviews 20150101 1

Alcohol use disorder (AUD) is a chronic heritable brain disorder with a variable clinical presentation. This variability, or heterogeneity, in clinical presentation suggests complex interactions between environmental and biological factors, resulting in several underlying pathophysiological mechanisms in the development and progression of AUD. Classifying AUD into subgroups of common clinical or pathological characteristics would ease the complexity of teasing apart underlying molecular mechanis ...[more]

PMID: 26259086

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Project description:BackgroundAlcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline.MethodsIndividuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long "practice quit attempt" while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions.DiscussionThe successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials.Trial registrationClinicalTrials.gov NCT04249882 . Registered on 31 January 2020.

Dataset Information

Advances in Medications and Tailoring Treatment for Alcohol Use Disorder.

Publications

Advances in Medications and Tailoring Treatment for Alcohol Use Disorder.

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