Alcohol & Alcoholism Vol. 39, No. 3, pp. 166-177, 2004
Alcohol & Alcoholism Vol. 39, No. 3 © Medical Council on Alcohol 2004; all rights reserved
REVIEW
PHARMACOTHERAPEUTIC TRIALS IN ADOLESCENT ALCOHOL USE DISORDERS: OPPORTUNITIES AND CHALLENGES
Division of Alcohol and Drug Addiction, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
* Author to whom correspondence should be addressed at: Division of Alcohol and Drug Addiction, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, Mail Code 7793, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA. Tel.: +210 562 5454; Fax: +210 562 5403; E-mail: dawes{at}uthscsa.edu
(Received 15 November 2003; in revised form 13 January 2004; accepted 14 January 2004)
Medications as adjuncts to psychosocial treatments for adolescent alcohol use disorders hold the promise of improved efficacy over psychosocial treatments alone. Specific components should be included in the design and implementation of these medication studies. Included should be assessment of the developmental risks of the chosen medication, consideration of short-term effects on the clinical disorder, factors affecting compliance and retention, age-specific pharmacokinetics, and systematic safety monitoring. A risk–benefit analysis should be conducted on the potential benefits of the medication to decrease alcohol use versus the potential long-term effects of medication use on brain development. To select clinically meaningful subtypes of adolescents with alcohol use disorders for medication trials, classification systems should be derived from multi-factorial models of complex neurodevelopmental disorders. Multi-factorial models will be required to select samples wherein specific gene–gene and gene–environment interactions predict medication treatment response. In samples of adolescents with alcohol use disorders, clinically meaningful subtypes are likely to have differential medication treatment response as a function of age of onset, family history of disorder, and comorbid psychopathology. Findings from preclinical and treatment studies in adults, along with pilot treatment findings in adolescents, suggest that particular serotonergic agents, opioid antagonists, and agents that modulate excitatory amino acids and GABAergic transmission might be effective. Future medication trials for adolescents with alcohol use disorders should use specific combinations of medications, based on specific hypotheses involving key neurotransmitter systems that putatively modulate treatment response. Combinations of medications may have additive effects on particular neurotransmitter systems or synergistic effects across two or more neurotransmitter systems, to further decrease alcohol consumption when compared with single-agent treatment.
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