Pharmacotherapeutic Trials in Adolescent Alcohol Use Disorders: Opportunities and Challenges

Dawes, Michael A.; Johnson, Bankole A.

doi:10.1093/alcalc/agh045

Cited by 25 publications

(11 citation statements)

References 134 publications

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“…Although pharmacotherapy is a common adjunct to psychosocial interventions for adolescents with AUDs, limited empirical evidence is available, and developmentally tailored studies are needed. 144 For example, despite the high rates of psychiatric comorbidity among youths with alcohol and other drug problems, few behavioral or pharmacologic studies have focused on these populations. 145 Treatment outcome studies clearly indicate the disadvantage to abusing/dependent youths of concomitant axis I mental health disorders and distinctive process and context differences challenging such youths.…”

Section: Developmental Context and Traditional Treatment Effortsmentioning

confidence: 99%

A Developmental Perspective on Alcohol and Youths 16 to 20 Years of Age

Brown¹,

McGue²,

et al. 2008

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Late adolescence (ie, 16 -20 years of age) is a period characterized by escalation of drinking and alcohol use problems for many and by the onset of an alcohol use disorder for some. This heightened period of vulnerability is a joint consequence of the continuity of risk from earlier developmental stages and the unique neurologic, cognitive, and social changes that occur in late adolescence. We review the normative neurologic, cognitive, and social changes that typically occur in late adolescence, and we discuss the evidence for the impact of these transitions on individual drinking trajectories. We also describe evidence linking alcohol abuse in late adolescence with neurologic damage and social impairments, and we discuss whether these are the bases for the association of adolescent drinking with increased risks of mental health, substance abuse, and social problems in adulthood. Finally, we discuss both the challenges and successes in the treatment and prevention of adolescent drinking problems. I N THE UNITED States, alcohol involvement sometimes starts but more often escalates between 16 and 20 years of age, when youths are also experiencing dramatic physical, emotional, and social changes. Specifically, a variety of forms of hazardous drinking emerge during middle to late adolescence and, for many youths, these problematic patterns of drinking continue to escalate through 18 to 20 years of age, the period of greatest risk for the onset of an alcohol use disorder (AUD).In seeking to understand youth development and alcohol involvement, it is important to consider all dimensions of functioning, because the interrelated cognitive, biological, social, and affective changes that occur during adolescence not only affect each another but also influence an individual's risk of problem drinking. In particular, the timing, sequence, and synchrony of developmentally specific transitions can affect how well youths master new roles, as well as continuities and discontinuities in their behavior. Therefore, developmental models representing a range of theoretical orientations, including systems theory, behavioral genetics, and developmental psychopathology, hold great promise for advancing our understanding of the processes that underlie adolescent changes, including the emergence of alcohol use and abuse.The need for developmental approaches is underscored by the existence of a consistent body of research showing that the escalation in drinking and the emergence of AUDs in middle and late adolescence have behavioral, social, and biological roots from earlier developmental stages. Moreover, it is becoming increasingly clear that alcohol involvement in adolescence has both short-and long-term effects on health and well-being at later developmental stages. Importantly, the consequences of adolescent drinking seem to differ from those associated with adult drinking, because there is increasing evidence that adolescents are especially vulnerable to the adverse effects of heavy alcohol use on both biological and socia...

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Section: Developmental Context and Traditional Treatment Effortsmentioning

confidence: 99%

A Developmental Perspective on Alcohol and Youths 16 to 20 Years of Age

Brown¹,

McGue²,

et al. 2008

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“…Based on a convergence of literature suggesting that age and gender are important factors to consider when developing a translational approach (Greenfield et al, 2010, Dawes and Johnson, 2004), we tested the first general hypothesis that both influence binge alcohol consumption.…”

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confidence: 99%

Bioinformatics Analyses Reveal Age-Specific Neuroimmune Modulation as a Target for Treatment of High Ethanol Drinking

Agrawal

Owen

Levin

et al. 2013

Alcohol Clin Exp Res

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Background Use of in silico bioinformatics analyses has led to important leads in the complex nature of alcoholism at the genomic, epigenomic, and proteomic level, but has not previously been successfully translated to the development of effective pharmacotherapies. In this study, a bioinformatics approach led to the discovery of neuroimmune pathways as an age-specific druggable target. Minocycline, a neuroimmune modulator, reduced high ethanol drinking in adult, but not adolescent, mice as predicted a priori. Methods Age and sex-divergent effects in alcohol consumption were quantified in FVB/NJ × C57BL/6J F1 mice given access to 20% alcohol using a 4 hr/day, 4-day Drinking-In-Dark (DID) paradigm. In silico bioinformatics pathway over-representation analysis for age-specific effects of alcohol in brain was performed using gene expression data collected in control and DID-treated, adolescent and adult, male mice. Minocycline (50 mg/kg i.p., once daily) or saline alone was tested for an effect on ethanol intake in the F1 and C57BL/6J (B6) mice across both age and gender groups. Effects of minocycline on the pharmacokinetic properties of alcohol were evaluated by comparing the rates of ethanol elimination between the saline and minocycline treated F1 and B6 mice. Results Age and gender differences in DID consumption were identified. Only males showed a clear developmental increase difference in drinking over time. In silico analyses revealed neuroimmune-related pathways as significantly over-represented in adult, but not adolescent, male mice. As predicted, minocycline treatment reduced drinking in adult, but not adolescent, mice. The age effect was present for both genders, and in both the F1 and B6 mice. Minocycline had no effect on the pharmacokinetic elimination of ethanol. Conclusions Our results are a proof of concept that bioinformatics analysis of brain gene expression can lead to the generation of new hypotheses and a positive translational outcome for individualized pharmacotherapeutic treatment of high alcohol consumption.

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“…Gastrointestinal symptoms were the most common adverse event (Toren et al 2005). There are no published studies of this agent in adolescents with SUD, although Dawes and Johnson have reported successful reductions in alcohol consumption in a small open-label (n = 12) trial of ondansetron (Dawes and Johnson 2004).…”

Section: Anticraving Agentsmentioning

confidence: 99%

“…The average daily dose of 50 mg was well tolerated. However, others have reported that the 50-mg dose produces significant nausea in adolescents, requiring the use of lower doses (Dawes and Johnson 2004).…”

Section: Anticraving Agentsmentioning

confidence: 99%

“…The generalizability of the diagnostic criteria and treatment data, including pharmacotherapeutic response, from adulthood to adolescence remains unclear, highlighted by the recent concerns over the use of antidepressants in children (Brent and Birmaher 2004;Bukstein et al 1989;Dawes and Johnson 2004;USFDA 2005). However, there has been a sharp increase in the prescription of psychotropic medications in youths over the past decade, including those with SUD (Delate et al 2004;Zito et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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