Adinoff B
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston.
Alcohol Clin Exp Res. 1994 Aug;18(4):873-8. doi: 10.1111/j.1530-0277.1994.tb00053.x.
Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the alpha 2-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam (n = 6), the alpha 2-receptor agonist clonidine (n = 7), the benzodiazepine alprazolam (this is also purported to have alpha 2-receptor agonist properties) (n = 6), and placebo (n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its alpha 2-receptor agonist properties.
在酒精戒断综合征期间，γ-氨基丁酸（GABA）抑制作用的减弱（去抑制）和交感神经系统的激活均会表现出来。本研究旨在探究对这两个生物系统有不同影响的药物的相对疗效：苯二氮䓬类药物可减轻GABA能去抑制作用，α2-肾上腺素能受体激动剂可降低交感神经激活。对苯二氮䓬类药物地西泮（n = 6）、α2受体激动剂可乐定（n = 7）、苯二氮䓬类药物阿普唑仑（据称也具有α2受体激动剂特性）（n = 6）和安慰剂（n = 6）在减轻酒精戒断体征和症状方面的有效性进行了评估。采用双盲设计，对无药物依赖的酒精依赖患者给予这4种药物中的1种，直至通过酒精戒断临床评估修订版测量的戒断症状得到成功治疗。在减轻戒断症状方面，阿普唑仑比可乐定和安慰剂均显著更有效。在地西泮对某些戒断指标的影响上，其比可乐定和安慰剂更有效。可乐定降低收缩压的幅度明显大于其他两种活性药物和安慰剂，但在减轻其他戒断症状方面并不比安慰剂更有效。与地西泮或安慰剂相比，阿普唑仑对血压的降低作用不显著。尽管样本量较小，但这些初步研究结果表明，阿普唑仑在治疗酒精戒断方面的疗效与其对苯二氮䓬受体的作用有关，而非其α-2受体激动剂特性。
