托吡酯
抗惊厥药物托吡酯可能对不能或不愿接受脱瘾治疗的患者有效。与安慰剂相比,研究发现托吡酯在随机对照试验中可减少成瘾和戒断症状,明显改善酒精中毒患者的躯体和心理状态。酒精依赖预防复发/促进戒酒:有高质量证据表明,与安慰剂相比,托吡酯可以减轻酗酒者的渴求和戒断症状,并显著改善他们的躯体和社会心理状态。[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[101]Johnson BA, Ait-Daoud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet. 2003 May 17;361(9370):1677-85.http://www.ncbi.nlm.nih.gov/pubmed/12767733?tool=bestpractice.com[102]Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007 Oct 10;298(14):1641-51.http://jama.ama-assn.org/cgi/content/full/298/14/1641http://www.ncbi.nlm.nih.gov/pubmed/17925516?tool=bestpractice.com[103]Johnson BA, Rosenthal N, Capece JA, et al. Improvement of physical health and quality of life of alcohol-dependent individuals with topiramate treatment: US multisite randomized controlled trial. Arch Intern Med. 2008 Jun 9;168(11):1188-99.http://www.ncbi.nlm.nih.gov/pubmed/18541827?tool=bestpractice.com[104]Shinn AK, Greenfield SF. Topiramate in the treatment of substance-related disorders: a critical review of the literature. J Clin Psychiatry. 2010 May;71(5):634-48.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736141/http://www.ncbi.nlm.nih.gov/pubmed/20361908?tool=bestpractice.com[105]Kenna GA, Lomastro TL, Schiesl A, et al. Review of topiramate: an antiepileptic for the treatment of alcohol dependence. Curr Drug Abuse Rev. 2009 May;2(2):135-42.http://www.ncbi.nlm.nih.gov/pubmed/19630744?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 它使重度饮酒天数的比例下降超过 23%,节制饮酒的平均天数几乎增加 3 天。[106]Arbaizar B, Diersen-Sotos T, Gómez-Acebo I, et al. Topiramate in the treatment of alcohol dependence: a meta-analysis. Actas Esp Psiquiatr. 2010 Jan-Feb;38(1):8-12.http://www.actaspsiquiatria.es/repositorio//11/61/ENG/11-61-ENG-8-12-152670.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/20931405?tool=bestpractice.com 重要的是,饮酒者在开始用药时就出现疗效。[107]Swift RM. Topiramate for the treatment of alcohol dependence: initiating abstinence. Lancet. 2003 May 17;361(9370):1666-7.http://www.ncbi.nlm.nih.gov/pubmed/12767727?tool=bestpractice.com 一项研究发现,含有编码氨酸受体蛋白纯合子基因的个体在使用托吡酯治疗后,重度饮酒天数减少。[108]Kranzler HR, Covault J, Feinn R, et al. Topiramate treatment for heavy drinkers: moderation by a GRIK1 polymorphism. Am J Psychiatry. 2014 Apr;171(4):445-52.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997125/http://www.ncbi.nlm.nih.gov/pubmed/24525690?tool=bestpractice.com
昂丹司琼
在随机对照试验中,这种选择性 5-HT3 拮抗剂对接受行为治疗的酒精使用障碍患者的结局改善是有效的。具体而言,当把这些患者分为早发型酒精中毒(EOA;25 岁以前发病)和晚发型酒精中毒(25 岁以后发病)时,昂丹司琼对 EOA 患者有效。[109]Johnson BA, Roache JD, Javors MA, et al. Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: a randomized controlled trial. JAMA. 2000 Aug 23-30;284(8):963-71.http://jama.ama-assn.org/cgi/reprint/284/8/963.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/10944641?tool=bestpractice.com酒精依赖预防复发/促进戒酒:有中等质量证据表明昂丹司琼是酒精依赖患者的有效治疗药物。该证据仅限于早发(25岁以前)型酗酒患者。[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[109]Johnson BA, Roache JD, Javors MA, et al. Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: a randomized controlled trial. JAMA. 2000 Aug 23-30;284(8):963-71.http://jama.ama-assn.org/cgi/reprint/284/8/963.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/10944641?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。 研究表明,对于有 5-HTT 基因 (LL/LS/SS) 特定基因型的患者,昂丹司琼可能对减少饮酒量和在增加戒酒尤其有帮助。[110]Johnson BA, Ait-Daoud N, Seneviratne C, et al. Pharmacogenetic approach at the serotonin transporter gene as a method of reducing the severity of alcohol drinking. Am J Psychiatry. 2011 Mar;168(3):265-75.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063997/http://www.ncbi.nlm.nih.gov/pubmed/21247998?tool=bestpractice.com
选择性 5 羟色胺再摄取抑制剂 (SSRI)
SSRI 对酒依赖的治疗是有效的。与安慰剂相比,舍曲林能减少治疗期间饮酒天数的比例,并且增加持续戒酒患者的数量。[111]Pettinati HM, Volpicelli JR, Kranzler HR, et al. Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype. Alcohol Clin Exp Res. 2000 Jul;24(7):1041-9.http://www.ncbi.nlm.nih.gov/pubmed/10924008?tool=bestpractice.com 然而,虽然 A 型(严重程度较低/晚发)酗酒者能出现相当大程度的改善,但与服用安慰剂者相比,B 型(严重程度较高/早发)酗酒者实际上饮酒时间更多(无显著性差异)。该结果说明,在酒依赖中舍曲林可能只对严重程度较低的酗酒者有效。[111]Pettinati HM, Volpicelli JR, Kranzler HR, et al. Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype. Alcohol Clin Exp Res. 2000 Jul;24(7):1041-9.http://www.ncbi.nlm.nih.gov/pubmed/10924008?tool=bestpractice.com酒精依赖预防复发/促进戒酒:有低质量证据表明 SSRI 是治疗酒精依赖患者的有效药物。有部分证据认为特定类型的酒精依赖患者使用后可能获益。[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[111]Pettinati HM, Volpicelli JR, Kranzler HR, et al. Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype. Alcohol Clin Exp Res. 2000 Jul;24(7):1041-9.http://www.ncbi.nlm.nih.gov/pubmed/10924008?tool=bestpractice.com[112]Kranzler HR, Burleson JA, Brown J, et al. Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res. 1996 Dec;20(9):1534-41.http://www.ncbi.nlm.nih.gov/pubmed/8986200?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。 选择性 5-羟色胺再摄取抑制剂在英国并未批准用于治疗酒精使用障碍,英国国家卫生与临床优化研究所不建议使用选择性 5-羟色胺再摄取抑制剂治疗无抑郁障碍的酒精依赖患者。[82]National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. February 2011 [internet publication].https://www.nice.org.uk/guidance/cg115 关于氟西汀治疗酒精依赖的临床试验得到了类似的结果,即氟西汀(60 mg/天)对 A 型(严重程度低/晚发)酒精使用障碍患者更有效。[112]Kranzler HR, Burleson JA, Brown J, et al. Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res. 1996 Dec;20(9):1534-41.http://www.ncbi.nlm.nih.gov/pubmed/8986200?tool=bestpractice.com 然而,并不是所有的研究都支持 SSRI 在酒精使用障碍治疗方面的应用。一项针对氟西汀治疗抑郁合并酒精使用障碍患者的研究发现,与安慰剂相比,氟西汀在治疗抑郁或饮酒方面均没有明显获益。[113]Cornelius JR, Bukstein OG, Wood DS, et al. Double-blind placebo-controlled trial of fluoxetine in adolescents with comorbid major depression and an alcohol use disorder. Addict Behav. 2009 Oct;34(10):905-9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720419/http://www.ncbi.nlm.nih.gov/pubmed/19321268?tool=bestpractice.com
巴氯芬
临床研究表明 γ-氨基丁酸-B 激动剂巴氯芬在减少酒精戒断综合征症状的疗效方面与地西泮的相当。[15]Leggio L, Kenna GA, Swift RM. New developments for the pharmacological treatment of alcohol withdrawal syndrome: a focus on non-benzodiazepine GABAergic medications. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jul 1;32(5):1106-17.http://www.ncbi.nlm.nih.gov/pubmed/18029075?tool=bestpractice.com[114]Addolorato G, Leggio L, Abenavoli L, et al. Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam. Am J Med. 2006 Mar;119(3):276.e13-8.http://www.ncbi.nlm.nih.gov/pubmed/16490478?tool=bestpractice.com酒精依赖预防复发/促进戒酒:有中等质量证据表明巴氯芬是酒精依赖患者的有效治疗药物。在有肝硬化的酒精依赖患者中,也有良好的安全性。[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[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[114]Addolorato G, Leggio L, Abenavoli L, et al. Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam. Am J Med. 2006 Mar;119(3):276.e13-8.http://www.ncbi.nlm.nih.gov/pubmed/16490478?tool=bestpractice.com[115]Addolorato G, Caputo F, Capristo E, et al. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol. 2002 Sep-Oct;37(5):504-8.http://www.ncbi.nlm.nih.gov/pubmed/12217947?tool=bestpractice.com[116]Addolorato G, Leggio L, Agabio R, et al. Baclofen: a new drug for the treatment of alcohol dependence. Int J Clin Pract. 2006 Aug;60(8):1003-8.http://www.ncbi.nlm.nih.gov/pubmed/16893442?tool=bestpractice.com[117]Addolorato G, Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007 Dec 8;370(9603):1915-22.http://www.ncbi.nlm.nih.gov/pubmed/18068515?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。 此外,因为它能减少酗酒者的酒精摄入和渴求,从而能有效预防复发。[115]Addolorato G, Caputo F, Capristo E, et al. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol. 2002 Sep-Oct;37(5):504-8.http://www.ncbi.nlm.nih.gov/pubmed/12217947?tool=bestpractice.com[116]Addolorato G, Leggio L, Agabio R, et al. Baclofen: a new drug for the treatment of alcohol dependence. Int J Clin Pract. 2006 Aug;60(8):1003-8.http://www.ncbi.nlm.nih.gov/pubmed/16893442?tool=bestpractice.com 巴氯芬在这些研究中表现出良好的耐受性、副作用较少,并且未发现成瘾性。巴氯芬的有效性和安全性在新近针对酒精使用障碍合并肝硬化患者的治疗中得到了验证,该类人群在抗渴求药物的临床试验中一般被排除在外。[117]Addolorato G, Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007 Dec 8;370(9603):1915-22.http://www.ncbi.nlm.nih.gov/pubmed/18068515?tool=bestpractice.com 一项系统评价指出,将来需要更多的研究去阐明该药物的最佳适用人群,以及有效剂量和治疗时长。尽管它不是酒精依赖药物治疗的一线推荐药物,由于其安全性,对有肝硬化的患者可能尤其有用。[118]Muzyk AJ, Rivelli SK, Gagliardi JP. Defining the role of baclofen for the treatment of alcohol dependence: a systematic review of the evidence. CNS Drugs. 2012 Jan 1;26(1):69-78.http://www.ncbi.nlm.nih.gov/pubmed/22145707?tool=bestpractice.com
其他抗惊厥药物
尽管纳入分析的研究质量不高且存在异质性,一项 2014 年的 Cochrane 评价发现,与安慰剂和纳曲酮相比,抗惊厥药物(例如丙戊酸、加巴喷丁)在几项饮酒研究中显示出一些获益。[119]Pani PP, Trogu E, Pacini M, et al. Anticonvulsants for alcohol dependence. Cochrane Database Syst Rev. 2014 Feb 13;(2):CD008544.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008544.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24523233?tool=bestpractice.com 在一项单独的随机对照试验中,与安慰剂相比,加巴喷丁在提高戒酒率和减少重度饮酒天数方面更有效,服用的剂量越高结果明显更好。[120]Mason BJ, Quello S, Goodell V, et al. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014 Jan;174(1):70-7.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920987/http://www.ncbi.nlm.nih.gov/pubmed/24190578?tool=bestpractice.com
以电脑和互联网为基础的干预措施
基于电脑和互联网的干预措施是实施简短干预的新形式,可能对减少问题性酒精使用和行为问题有效。[121]Tait RJ, Christensen H. Internet-based interventions for young people with problematic substance use: a systematic review. Med J Aust. 2010 Jun 7;192(11 suppl):S15-21.http://www.ncbi.nlm.nih.gov/pubmed/20528701?tool=bestpractice.com[122]Carey KB, Scott-Sheldon LA, Elliott JC, et al. Computer-delivered interventions to reduce college student drinking: a meta-analysis. Addiction. 2009 Nov;104(11):1807-19.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763045/http://www.ncbi.nlm.nih.gov/pubmed/19744139?tool=bestpractice.com 一项包含 9 项研究的评价结果支持这些治疗对促进正性行为改变的可能性,但由于缺乏基于电脑和互联网的标准化治疗,需要进行更多的研究来完善。[123]Gainsbury S, Blaszczynski A. A systematic review of internet-based therapy for the treatment of addictions. Clin Psychol Rev. 2011 Apr;31(3):490-8.http://www.ncbi.nlm.nih.gov/pubmed/21146272?tool=bestpractice.com 一项 meta 分析评估了面对面干预和基于电脑的干预在减少酒精使用方面的相对有效性,发现与基于电脑的干预相比,面对面干预可使饮酒量减少更多,并能在更长的时间内维持这些获益。[124]Carey KB, Scott-Sheldon LA, Elliott JC, et al. Face-to-face versus computer-delivered alcohol interventions for college drinkers: a meta-analytic review, 1998 to 2010. Clin Psychol Rev. 2012 Dec;32(8):690-703.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511828/http://www.ncbi.nlm.nih.gov/pubmed/23022767?tool=bestpractice.com 研究表明,在大学生中,专门设计的通过电脑实施的干预对问题性饮酒的治疗和预防有一定作用。[125]Bingham CR, Barretto AI, Walton MA, et al. Efficacy of a web-based, tailored, alcohol prevention/intervention program for college students: initial findings. J Am Coll Health. 2010 Jan-Feb;58(4):349-56.http://www.ncbi.nlm.nih.gov/pubmed/20159758?tool=bestpractice.com[126]Carey KB, Carey MP, Henson JM, et al. Brief alcohol interventions for mandated college students: comparison of face-to-face counseling and computer-delivered interventions. Addiction. 2011 Mar;106(3):528-37.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058775/http://www.ncbi.nlm.nih.gov/pubmed/21059184?tool=bestpractice.com