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A review of pharmacogenetic studies of substance-related disorders.

ABSTRACT: Substance-related disorders (SRDs) are a major cause of morbidity and mortality worldwide. Family, twin, and adoption studies have demonstrated the substantial heritability of SRDs. To determine the impact of genetic variation on risk for SRD and the response to treatment, researchers have conducted a number of secondary data analyses and quasi-experimental studies that target one or more candidate gene variants.This review examines studies in which candidate polymorphisms were examined as mediator variables to identify pharmacogenetic effects on subjective responses to drug administration or cues or outcomes of medication trials for SRDs. Efforts to use a meta-analytic approach to quantify these effects are premature because the number of available studies using similar methods and outcomes is limited, so the present review is qualitative.Findings from these studies provide preliminary evidence of clinically relevant pharmacogenetic effects. However, independent replication of these findings has been sparse.Although this growing body of literature has produced conflicting results, improved statistical controls may help to clarify the findings. Additionally, the use of empirically derived sub-phenotypes (i.e., which serve to differentiate distinct groups of affected individuals) may also help to identify genetic mediators of pharmacologic response in relation to SRDs. The identification of genetic mediators can inform clinical care both by identifying risk factors for SRDs and predicting adverse events and therapeutic outcomes associated with specific pharmacotherapies.

SUBMITTER: Jones JD

PROVIDER: S-EPMC4458176 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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A review of pharmacogenetic studies of substance-related disorders.

Jones Jermaine D JD Comer Sandra D SD

Drug and alcohol dependence 20150318

<h4>Background</h4>Substance-related disorders (SRDs) are a major cause of morbidity and mortality worldwide. Family, twin, and adoption studies have demonstrated the substantial heritability of SRDs. To determine the impact of genetic variation on risk for SRD and the response to treatment, researchers have conducted a number of secondary data analyses and quasi-experimental studies that target one or more candidate gene variants.<h4>Methods</h4>This review examines studies in which candidate p ...[more]

PMID: 25819021

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Project description:BackgroundYoung people are disproportionately more likely than other age groups to use substances. The rise in substance use and related harms, including overdose, during the Covid-19 pandemic has created a critical need for more innovative and accessible substance use interventions. Digital interventions have shown effectiveness and can provide more engaging, less stigmatizing, and accessible interventions that meet the needs of young people. This review provides an overview of recent literature on the nature of recently published digital interventions for young people in terms of technologies used, substances targeted, intended outcomes and theoretical or therapeutic models employed.MethodsRapid review methodology was used to identify and assess the literature on digital interventions for young people. An initial keyword search was conducted using MEDLINE the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA) and PROSPERO for the years 2015-2020, and later updated to December 2021. Following a title/abstract and full-text screening of articles, and consensus decision on study inclusion, the data extraction process proceeded using an extraction grid developed for the study. Data synthesis relied on an adapted conceptual framework by Stockings, et al. that involved a three-level treatment spectrum for youth substance use (prevention, early intervention, and treatment) for any type of substance.ResultsIn total, the review identified 43 articles describing 39 different digital interventions. Most were early interventions (n = 28), followed by prevention interventions (n = 6) and treatment interventions (n = 5). The identified digital technologies included web-based (n = 14), game-based (n = 10), mobile-based (n = 7), and computer-based (n = 5) technologies, and virtual reality (n = 3). Most interventions targeted alcohol use (n = 20) followed by tobacco/nicotine (n = 5), cannabis (n = 2), opioids (n = 2), ketamine (1) and multiple, or any substances (n = 9). Most interventions used a personalized or normative feedback approach and aimed to effect behaviour change as the intended outcome. Interestingly, a harm reduction approach guided only one of the 39 interventions.ConclusionsWhile web-based interventions represented the most common type of technology, more recently developed immersive and interactive technologies such as virtual reality and game-based interventions call for further exploration. Digital interventions focused mainly on alcohol use, reflecting less concern for tobacco, cannabis, co-occurring substance use, and illicit drug use. Specifically, the recent exacerbation in the opioid crisis throughout North American underlines the urgent need for more prevention-oriented digital interventions for opioid use. The uptake of digital interventions among youth also depends on the incorporation of harm reduction approaches.

Project description:BackgroundStudies of the genetic basis of drug response could help clarify mechanisms of drug action/metabolism, and facilitate development of genotype-based predictive tests of efficacy or toxicity (pharmacogenetics).ObjectivesWe conducted a systematic review and field synopsis of pharmacogenetic studies to quantify the scope and quality of available evidence in this field in order to inform future research.Data sourcesOriginal research articles were identified in Medline, reference lists from 24 meta-analyses/systematic reviews/review articles and U.S. Food and Drug Administration website of approved pharmacogenetic tests. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTION CRITERIA: We included any study in which either intended or adverse response to drug therapy was examined in relation to genetic variation in the germline or cancer cells in humans.Study appraisal and synthesis methodsStudy characteristics and data reported in abstracts were recorded. We further analysed full text from a random 10% subset of articles spanning the different subclasses of study.ResultsFrom 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive). A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25 ratio 1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40-222]) with no trend to an increase over time, generated a high proportion (74.5%) of nominally significant (p<0.05) reported associations suggesting the possibility of significance-chasing bias. Despite 136 examples of gene/drug interventions being the subject of >or=4 studies, only 31 meta-analyses were identified. The majority (69.4%) of end-points were continuous and likely surrogate rather than hard (binary) clinical end-points.Conclusions and implications of key findingsThe high expectation but limited translation of pharmacogenetic research thus far may be explained by the preponderance of reviews over primary research, small sample sizes, a mainly candidate gene approach, surrogate markers, an excess of nominally positive to truly positive associations and paucity of meta-analyses. Recommendations based on these findings should inform future study design to help realise the goal of personalised medicines. SYSTEMATIC REVIEW REGISTRATION NUMBER: Not Registered.

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A review of pharmacogenetic studies of substance-related disorders.

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A review of pharmacogenetic studies of substance-related disorders.

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