Targeted opioid receptor antagonists in the treatment of alcohol use disorders.
Targeted opioid receptor antagonists in the treatment of alcohol use disorders.
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针对性的阿片类受体拮抗剂在治疗酒精使用障碍方面。
DOI：
10.1007/s40263-013-0096-4
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发表时间：
2013-10
期刊：
影响因子：
6
通讯作者：
Arias AJ
中科院分区：
文献类型：
--
作者：
Niciu MJ;Arias AJ
1994年，美国食品和药物管理局批准μ阿片受体拮抗剂纳曲酮治疗酒精依赖。然而，在物质滥用人群中，需要每天服用纳曲酮的治疗并不一致，持续的药物暴露可能会增加不良后果的风险，例如肝毒性。这促进了一种“有针对性的”或“按需”的阿片受体拮抗剂治疗方法，即仅在高危情况下或在高危情况下使用药物，包括强烈渴望的时间。关于靶向纳曲酮减少饮酒相关后果的能力的初步研究在问题饮酒者中进行，并已扩展到更大的、多地点、安慰剂对照的研究，结果是积极的。另一种μ阿片受体拮抗剂纳美芬已被研究在“根据需要”的基础上，以减少酒精依赖者的大量饮酒。这些研究包括在欧洲进行的三项大型多点试验，持续时间长达一年，并作为欧洲药品管理局最近批准纳美芬作为酒精依赖“按需”辅助治疗的基础。我们综述了阿片受体拮抗剂治疗反应的潜在调节因素，包括主观评估、客观临床措施和遗传变异。总之，使用阿片类拮抗剂进行有针对性的或“按需”治疗是一种有效的减少饮酒和酒精依赖问题的减害策略。
In 1994, the US Food and Drug Administration approved the μ-opioid receptor antagonist naltrexone to treat alcohol dependence. However, treatments requiring daily administration, such as naltrexone, are inconsistently adhered to in substance abusing populations, and constant medication exposure can increase risk of adverse outcomes, e.g., hepatotoxicity. This has fostered a ‘targeted’ or ‘as needed’ approach to opioid receptor antagonist treatment, in which medications are used only in anticipation of or during high-risk situations, including times of intense cravings. Initial studies of the ability of targeted naltrexone to reduce drinking-related outcomes were conducted in problem drinkers and have been extended into larger, multi-site, placebo-controlled investigations with positive results. Another μ-opioid receptor antagonist, nalmefene, has been studied on an ‘as-needed’ basis to reduce heavy drinking in alcohol-dependent individuals. These studies include three large multi-site trials in Europe of up to 1 year in duration, and serve as the basis for the recent approval of nalmefene by the European Medicines Agency as an ‘as-needed’ adjunctive treatment for alcohol dependence. We review potential moderators of opioid receptor antagonist treatment response including subjective assessments, objective clinical measures and genetic variants. In sum, the targeted or ‘as-needed’ approach to treatment with opioid antagonists is an efficacious harmreduction strategy for problem drinking and alcohol dependence.