针对经选择患者组全部患者的治疗推荐
第一选择
纳曲酮
:
50-100 mg,每日一次,持续 12-16 周;380 mg,肌内注射,每月一次,持续6个月
或
阿坎酸
:
666 mg,口服,每日 3 次,持续 12-16 周
或
双硫仑
:
初始剂量 500 mg,口服,每日一次,持续一周,之后剂量 250 mg,每日一次
或
纳美芬
:
需要时当天口服 18 mg,最好在预期饮酒时间之前 1-2 小时
批准用于酒精使用障碍的治疗药物主要作用于神经生物系统,该系统被认为负责酒精渴求、酒精的强化和奖赏效应,以及成瘾作用,目标是降低饮酒的冲动,因此而帮助患者维持戒酒。[2]Swift RM. Drug therapy for alcohol dependence. N Engl J Med. 1999 May 13;340(19):1482-90.http://www.ncbi.nlm.nih.gov/pubmed/10320388?tool=bestpractice.com[52]Lingford-Hughes AR, Welch S, Peter L, et al. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. J Psychopharmacol. 2012 Jul;26(7):899-952.http://www.ncbi.nlm.nih.gov/pubmed/22628390?tool=bestpractice.com[66]Swift R. Emerging approaches to managing alcohol dependence. Am J Health Syst Pharm. 2007 Mar 1;64(5 suppl 3):S12-22.http://www.ncbi.nlm.nih.gov/pubmed/17322178?tool=bestpractice.com[70]Addolorato G, Abenavoli L, Leggio L, et al. How many cravings? Pharmacological aspects of craving treatment in alcohol addiction: a review. Neuropsychobiology. 2005;51(2):59-66.http://www.ncbi.nlm.nih.gov/pubmed/15741745?tool=bestpractice.com[71]Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76.http://www.ncbi.nlm.nih.gov/pubmed/16545872?tool=bestpractice.com[72]Addolorato G, Armuzzi A, Gasbarrini G, et al. Pharmacological approaches to the management of alcohol addiction. Eur Rev Med Pharmacol Sci. 2002 Sep-Oct;6(5):89-97.http://www.ncbi.nlm.nih.gov/pubmed/12776801?tool=bestpractice.com
阿片类拮抗剂纳曲酮有口服和长效制剂(注射用)两种剂型,尤其适用于有酒精使用障碍家族史的患者以及有显著酒精成瘾的患者。酒精依赖预防复发/促进戒酒:中等质量证据表明纳曲酮(口服和缓释)对酒精依赖患者有效。 [52]Lingford-Hughes AR, Welch S, Peter L, et al. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. J Psychopharmacol. 2012 Jul;26(7):899-952.http://www.ncbi.nlm.nih.gov/pubmed/22628390?tool=bestpractice.com[66]Swift R. Emerging approaches to managing alcohol dependence. Am J Health Syst Pharm. 2007 Mar 1;64(5 suppl 3):S12-22.http://www.ncbi.nlm.nih.gov/pubmed/17322178?tool=bestpractice.com[70]Addolorato G, Abenavoli L, Leggio L, et al. How many cravings? Pharmacological aspects of craving treatment in alcohol addiction: a review. Neuropsychobiology. 2005;51(2):59-66.http://www.ncbi.nlm.nih.gov/pubmed/15741745?tool=bestpractice.com[71]Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76.http://www.ncbi.nlm.nih.gov/pubmed/16545872?tool=bestpractice.com[72]Addolorato G, Armuzzi A, Gasbarrini G, et al. Pharmacological approaches to the management of alcohol addiction. Eur Rev Med Pharmacol Sci. 2002 Sep-Oct;6(5):89-97.http://www.ncbi.nlm.nih.gov/pubmed/12776801?tool=bestpractice.com[75]Anton RF, O'Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006 May 3;295(17):2003-17.http://jama.ama-assn.org/cgi/reprint/295/17/2003.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/16670409?tool=bestpractice.com[76]Bogenschutz MP, Scott Tonigan J, Pettinati HM. Effects of alcoholism typology on response to naltrexone in the COMBINE study. Alcohol Clin Exp Res. 2009 Jan;33(1):10-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626136/http://www.ncbi.nlm.nih.gov/pubmed/18828797?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 当前正在饮酒的患者也可以使用。纳曲酮对最近或当前使用阿片类药物患者的戒断反应有增强作用,因此患者只有在停用阿片类数日后才能使用该药物。新出现的证据表明,具有特定 μ-阿片类受体基因型的酗酒者对阿片类拮抗剂的反应更好。纳曲酮疗效预测:有中等质量证据表明,纳曲酮效果受到 μ 阿片类受体基因 (OPPM1) 变异的调节,酗酒患者特定的临床类型(例如早发 vs 晚发)对纳曲酮疗效也有预测效果。这些结果可能对治疗选择有帮助。[76]Bogenschutz MP, Scott Tonigan J, Pettinati HM. Effects of alcoholism typology on response to naltrexone in the COMBINE study. Alcohol Clin Exp Res. 2009 Jan;33(1):10-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626136/http://www.ncbi.nlm.nih.gov/pubmed/18828797?tool=bestpractice.com[77]Anton RF, Oroszi G, O'Malley S, et al. An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666924/http://www.ncbi.nlm.nih.gov/pubmed/18250251?tool=bestpractice.com[78]Ooteman W, Naassila M, Koeter MW, et al. Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.http://www.ncbi.nlm.nih.gov/pubmed/19523047?tool=bestpractice.com[79]Ray LA, Hutchison KE. Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study. Arch Gen Psychiatry. 2007 Sep;64(9):1069-77.http://www.ncbi.nlm.nih.gov/pubmed/17768272?tool=bestpractice.com[80]Gueorguieva R, Wu R, Pittman B, et al. New insights into the efficacy of naltrexone based on trajectory-based reanalyses of two negative clinical trials. Biol Psychiatry. 2007 Jun 1;61(11):1290-5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1952242/http://www.ncbi.nlm.nih.gov/pubmed/17224132?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 长效制剂可能提高服药依从性,对正在饮酒的酒精依赖患者似乎没有肝脏毒性。[66]Swift R. Emerging approaches to managing alcohol dependence. Am J Health Syst Pharm. 2007 Mar 1;64(5 suppl 3):S12-22.http://www.ncbi.nlm.nih.gov/pubmed/17322178?tool=bestpractice.com[71]Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76.http://www.ncbi.nlm.nih.gov/pubmed/16545872?tool=bestpractice.com[83]Ciraulo DA, Dong Q, Silverman BL, et al. Early treatment response in alcohol dependence with extended-release naltrexone. J Clin Psychiatry. 2008 Feb;69(2):190-5.http://www.ncbi.nlm.nih.gov/pubmed/18348601?tool=bestpractice.com[84]Lucey MR, Silverman BL, Illeperuma A, et al. Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics. Alcohol Clin Exp Res. 2008 Mar;32(3):498-504.http://www.ncbi.nlm.nih.gov/pubmed/18241321?tool=bestpractice.com 尽管研究认为纳曲酮的总体效果比较微弱,但一项包含 22 项 RCT 的系统评价发现,这可能至少部分是由一些临床试验中的服药依从性差造成的。[81]Swift R, Oslin DW, Alexander M, et al. Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. J Stud Alcohol Drugs. 2011 Nov;72(6):1012-8.http://www.ncbi.nlm.nih.gov/pubmed/22051215?tool=bestpractice.com
阿坎酸是一种可稳定谷氨酸和 γ-氨基丁酸递质系统的药物,被批准用于维持酒精使用的戒断状态。用于已停止饮酒的患者时效果更好。酒精依赖预防复发/促进戒酒:有中等质量证据表明阿坎酸联合社会心理行为治疗对已经停酒的酒精依赖患者有促进维持戒酒的效果。[86]Rösner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004332.http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD004332/frame.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/20824837?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 研究综述发现阿坎酸可以降低复发风险,并增加戒酒持续时间。[86]Rösner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004332.http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD004332/frame.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/20824837?tool=bestpractice.com [
]Can acamprosate (with or without naltrexone) support continued abstinence after detoxification in alcohol-dependent people?https://cochranelibrary.com/cca/doi/10.1002/cca.577/full显示答案 一项针对 22 项研究的 meta 分析发现,阿坎酸在提高戒酒率、减少重度饮酒、改善治疗完成率和服药依从性方面优于安慰剂。[87]Mason BJ, Lehert P. Acamprosate for alcohol dependence: a sex-specific meta-analysis based on individual patient data. Alcohol Clin Exp Res. 2012 Mar;36(3):497-508.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288465/http://www.ncbi.nlm.nih.gov/pubmed/21895717?tool=bestpractice.com
双硫仑能阻断酒精代谢途径,造成毒性乙醛的积聚。因此双硫仑-酒精的相互作用会造成显著的全身性影响(脸红、恶心、腹泻、心动过速、高血压)。尽管该反应本质上作用时间通常短暂,但偶尔也可导致躯体并发症甚至死亡。由于每日服用双硫仑的依从性差,限制了其临床使用,通过配偶或其他家属的监督服药会增强效果。
纳美芬在结构上与纳曲酮类似,是 μ 阿片类受体的竞争性拮抗剂。除了用于阿片类过量治疗外,在欧洲它也被批准用于酒精使用障碍的治疗。一项 RCT 发现该药物有效,可以将复发率由 59% 降低为 37%。[88]Mason BJ, Salvato FR, Williams LD, et al. A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry. 1999 Aug;56(8):719-24.http://archpsyc.jamanetwork.com/article.aspx?articleid=205228http://www.ncbi.nlm.nih.gov/pubmed/10435606?tool=bestpractice.com 当酒精使用障碍患者担心自己可能会饮酒时,应在当天服用纳美芬,最好是饮酒前 1-2 小时(但如果已经开始饮酒,越快越好)。美国市场已没有该药。
如果选择的第一种药物无效,需继续选择第二种。该序贯方案是常见的临床实践,但当前并没有已发表的研究能评估该方案的有效性。
目前没有证据支持药物联合治疗;评估这一问题的研究很少。
相关研究并未得出此类药物确切的用药时间间隔,因此采用灵活的方案支持患者努力是合理的。
对于酗酒和药物滥用,已经制定几种逐步治疗方案,将社火心理治疗和药物治疗结合了起来。[91]O'Malley SS, Carroll KM. Psychotherapeutic considerations in pharmacological trials: alcoholism, clinical and experimental research. Alcohol Clin Exp Res. 1996 Oct;20(7 suppl):17A-22A.http://www.ncbi.nlm.nih.gov/pubmed/8904990?tool=bestpractice.com[92]Pettinati HM, Volpicelli JR, Pierce JD, et al. Improving naltrexone response: an intervention for medical practitioners to enhance medication compliance in alcohol dependent patients. J Addict Dis. 2000;19(1):71-83.http://www.ncbi.nlm.nih.gov/pubmed/10772604?tool=bestpractice.com 这些方案包括患者教育、个性化反馈、情感支持、药物监测和增强动机。NIAAA: Helping patients who drink too much: a clinician's guide and related professional support resourcesNational Institute on Alcohol Abuse and Alcoholism (NIAAA) 一项包含 15项 RCT 的 meta 分析发现,当同时治疗酒精依赖及与其共存的抑郁和焦虑障碍时,酒精使用和精神障碍的结局会得到改善。[93]Hobbs JD, Kushner MG, Lee SS, et al. Meta-analysis of supplemental treatment for depressive and anxiety disorders in patients being treated for alcohol dependence. Am J Addict. 2011 Jul-Aug;20(4):319-29.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124006/http://www.ncbi.nlm.nih.gov/pubmed/21679263?tool=bestpractice.com