Dawes Michael A, Johnson Bankole A
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
Alcohol Alcohol. 2004 May-Jun;39(3):166-77. doi: 10.1093/alcalc/agh045.
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.
药物作为青少年酒精使用障碍心理社会治疗的辅助手段，有望比单纯的心理社会治疗更有效。这些药物研究的设计和实施应包括特定的组成部分。应包括对所选药物发育风险的评估、对临床疾病短期影响的考虑、影响依从性和持续性的因素、特定年龄的药代动力学以及系统的安全监测。应对药物减少酒精使用的潜在益处与药物使用对大脑发育的潜在长期影响进行风险效益分析。为了选择有临床意义的青少年酒精使用障碍亚型进行药物试验，分类系统应源自复杂神经发育障碍的多因素模型。需要多因素模型来选择样本，其中特定的基因-基因和基因-环境相互作用可预测药物治疗反应。在青少年酒精使用障碍样本中，有临床意义的亚型可能因发病年龄、疾病家族史和共病精神病理学而有不同的药物治疗反应。来自成人临床前和治疗研究的结果，以及青少年的试点治疗结果表明，特定的血清素能药物、阿片类拮抗剂以及调节兴奋性氨基酸和GABA能传递的药物可能有效。未来针对青少年酒精使用障碍的药物试验应基于涉及假定调节治疗反应的关键神经递质系统的特定假设，使用特定的药物组合。与单药治疗相比，药物组合可能对特定神经递质系统有相加作用，或在两个或多个神经递质系统之间有协同作用，以进一步减少酒精消费。
