Antiglutamatergic strategies for ethanol detoxification: Comparison with placebo and diazepam
Antiglutamatergic strategies for ethanol detoxification: Comparison with placebo and diazepam
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DOI：
10.1111/j.1530-0277.2007.00344.x
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发表时间：
2007-04-01
影响因子：
3.2
通讯作者：
Krystal, John H.
中科院分区：
文献类型：
--
作者：
Krupitsky, Evgeny M.;Rudenko, Anatoly A.;Krystal, John H.
背景：苯二氮卓类药物是乙醇解毒的标准药物疗法，但对其滥用潜力和对过渡到戒酒的负面影响的担忧促使人们寻找新的治疗方法。谷氨酸能激活和谷氨酸受体上调有助于乙醇依赖和戒断。本研究比较了3种抗谷氨酸能的乙醇解毒策略与安慰剂和苯二氮卓类药物地西泮：谷氨酸释放抑制剂拉莫三嗪；n -甲基- d -天冬氨酸谷氨酸受体拮抗剂美金刚胺；以及AMPA/kainite受体抑制剂托吡酯。方法：这项安慰剂对照随机单盲精神药理学试验研究了127例有临床显著酒精戒断症状的男性酒精依赖住院患者。受试者被分配到5种治疗中的1种，为期7天：安慰剂、地西泮10mg TID、拉莫三嗪25mg QID、美金刚10mg TID或托吡酯25mg QID。当指定的药物不能充分抑制戒断症状时，额外给予地西泮。结果：与安慰剂相比，所有活性药物均显著降低了观察者评价和自我评价的戒断严重程度、烦躁情绪和补充地西泮给药。活性药物与地西泮没有区别。结论：本研究提供了第一个系统的临床证据，支持一些抗谷氨酸能方法治疗酒精戒断症状的有效性。这些数据支持了谷氨酸激活有助于人类戒酒的假设。现在需要对每一种药物进行明确的研究，以进一步评估它们治疗酒精戒断的有效性。
Background: Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N-methyl-D-aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate.Methods: This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately.Results: All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam.Conclusions: This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal.