Center for Drugs and Alcohol Programs, Department of Psychiatry, Medical University of South Carolina, USA.
CNS Neurol Disord Drug Targets. 2010 Mar;9(1):50-4. doi: 10.2174/187152710790966731.
Alcohol dependence is a costly and socially devastating illness. The dopamine system has received increased attention due to the consensus that dopaminergic dysfunction is at the core of the addiction process. Agents that modulate this system might be beneficial in reducing craving, reward, and relapse. Aripiprazole is a 3(rd) generation atypical antipsychotic U.S. Food and Drug Administration-approved for the treatment of schizophrenia, bipolar disorder, and treatment-resistant major depression. Its principal mechanism of action appears to be associated with partial agonism at the D2 dopamine receptor. Nevertheless, relatively recent pre-clinical data shows that aripiprazole might exert its action by way of agonism, partial agonism, and antagonism at both dopamine and serotonin receptors. In animal models of alcoholism aripiprazole produced an overall decrease in drinking behavior. Clinical trials with aripiprazole in alcoholics have shown some positive, but inconsistent, results. Given aripiprazole's putative activity on frontal-subcortical circuits subserving reward/craving and impulsive behavior, it might prove to be beneficial for neuropsychiatric conditions in which dysregulation of reward and impulsivity, among them alcoholism, are at the core of the syndrome. This article proposes a potential role for aripiprazole in alcoholism treatment, and suggests that more randomized controlled trials should be designed at appropriate doses to better understand aripiprazole's potential role as a treatment option. More options are needed to treat alcoholics that fall into different subgroups (e.g., those with impulsive disorders), or non-responsive to available treatments. Early results with aripiprazole are promising and warrant further exploration.
酒精依赖是一种代价高昂且具有社会破坏性的疾病。多巴胺系统受到了越来越多的关注，因为人们普遍认为多巴胺能功能障碍是成瘾过程的核心。调节该系统的药物可能有助于减少渴望、奖励和复发。阿立哌唑是一种第三代非典型抗精神病药，已获得美国食品和药物管理局批准，可用于治疗精神分裂症、双相情感障碍和治疗抵抗性重度抑郁症。其主要作用机制似乎与 D2 多巴胺受体的部分激动作用有关。然而，相对较新的临床前数据表明，阿立哌唑可能通过多巴胺和 5-羟色胺受体的激动、部分激动和拮抗作用发挥其作用。在酒精中毒的动物模型中，阿立哌唑总体上减少了饮酒行为。在酒精中毒患者中进行的阿立哌唑临床试验显示出一些积极但不一致的结果。鉴于阿立哌唑对负责奖励/渴望和冲动行为的额皮质下回路的假定活性，它可能对神经精神疾病有益，其中奖励和冲动调节紊乱是综合征的核心。本文提出了阿立哌唑在酒精中毒治疗中的潜在作用，并建议设计适当剂量的更多随机对照试验，以更好地了解阿立哌唑作为治疗选择的潜在作用。需要更多的选择来治疗属于不同亚组（例如，冲动障碍患者）或对现有治疗无反应的酗酒者。阿立哌唑的早期结果很有希望，值得进一步探索。
