酒精使用障碍的治疗包括药物、心理和社会干预,目的是减少或消除酒精对个体、家庭和家庭关系以及社会其他方面的有害影响。治疗通常包括以下部分:
脱毒治疗可能不是必需的,具体取决于依赖的严重性,但总是需要进行躯体评估和给出建议。康复和病后护理适用于中至重度的酒精使用障碍患者。
物质滥用治疗的方法和目标
物质使用障碍的治疗方法很多,有低成本、低强度的方法(例如停止饮酒的简短建议或者药物使用和自助计划),也有高成本、高强度的方法(例如住院脱毒治疗和康复计划)。有多种不同方案的治疗,最常使用的有医学/生物学方法和精神/宗教方法。
治疗目标的范围可从期望患者完全戒酒到与患者一起努力来达到控制饮酒。对于轻度酒精使用障碍/危险性饮酒患者,目标应为在有害性酒精使用的基础上减量。对于中到重度酒精使用障碍患者,最佳目标是帮助患者完全戒酒。如果不能完全戒酒,显著减少饮酒量对患者也很有好处。
问题性酒精使用和轻度酒精使用障碍
对于存在问题性酒精使用模式但不符合酒精使用障碍诊断标准(例如只符合一条诊断标准)的个体,以及轻度酒精使用障碍患者,经常通过简单的内科医生引导干预和/或医疗建议进行处理。在某些领域,也可由受过适当培训的酒精顾问或心理学家进行简短的干预。
简短干预可由一次或多次治疗组成,可在医生诊室或医院的其他地点(如急诊室或住院病房)实施,在此过程中针对患者的酒精使用问题及其后果给予支持性和共情的反馈。 [
]What are the effects of brief interventions in heavy alcohol users admitted to general hospital wards?https://cochranelibrary.com/cca/doi/10.1002/cca.593/full显示答案 理想情况下,患者和医生应一起制定减少或消除酒精使用的计划。一般说来,干预的次数越多效果越好。一项研究发现,相比单次干预,10 次干预在减少饮酒频率和饮酒量方面更有效。[55]Baker AL, Kavanagh DJ, Kay-Lambkin FJ, et al. Randomized controlled trial of cognitive-behavioural therapy for coexisting depression and alcohol problems: short-term outcome. Addiction. 2010 Jan;105(1):87-99.http://www.ncbi.nlm.nih.gov/pubmed/19919594?tool=bestpractice.com 针对 6 项 meta 分析和 1 篇系统评价的一项研究显示,短暂干预可中度减少酗酒者的酒精摄入,增加会谈或随访次数能带来更多益处。[56]Álvarez-Bueno C, Rodríguez-Martín B, García-Ortiz L, et al. Effectiveness of brief interventions in primary health care settings to decrease alcohol consumption by adult non-dependent drinkers: a systematic review of systematic reviews. Prev Med. 2015 Jul;76(suppl):S33-8.http://www.ncbi.nlm.nih.gov/pubmed/25514547?tool=bestpractice.com 然而,一项包括超过 800 例研究受试者的随机对照临床试验 (RCT) 显示,在由治疗师或计算机给予单次短暂干预后,未达法定年龄饮酒者的饮酒量和饮酒相关后果(例如酒后驾车事件和酒精相关损伤)减少。[57]Cunningham RM, Chermack ST, Ehrlich PF, et al. Alcohol interventions among underage drinkers in the ED: a randomized controlled trial. Pediatrics. 2015 Oct;136(4):e783-93.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586730/http://www.ncbi.nlm.nih.gov/pubmed/26347440?tool=bestpractice.com 该计划还需要包括效果评估(正规工具进行评估)以及医师后续随访。[58]Kaner EF, Beyer FR, Muirhead C, et al. Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database Syst Rev. 2018 Feb 24;(2):CD004148.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD004148.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29476653?tool=bestpractice.com减少饮酒量:高质量证据表明初级医疗机构内的简短干预对减少饮酒量比常规护理更有效。[58]Kaner EF, Beyer FR, Muirhead C, et al. Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database Syst Rev. 2018 Feb 24;(2):CD004148.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD004148.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29476653?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。
急诊科内的简短干预能增加戒酒的尝试,促使存在问题性酒精使用的青少年和成人减少危险情境下的饮酒。[59]Bernstein J, Heeren T, Edward E, et al. A brief motivational interview in a pediatric emergency department, plus 10-day telephone follow-up, increases attempts to quit drinking among youth and young adults who screen positive for problematic drinking. Acad Emerg Med. 2010 Aug;17(8):890-902.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913305/http://www.ncbi.nlm.nih.gov/pubmed/20670329?tool=bestpractice.com一项包含 22 项随机对照试验的 meta 分析发现,简短干预可减少男性饮酒,但缺乏足够数据证明其在女性中的有效性。[60]Kaner EF, Dickinson HO, Beyer F, et al. The effectiveness of brief alcohol interventions in primary care settings: a systematic review. Drug Alcohol Rev. 2009 May;28(3):301-23.http://www.ncbi.nlm.nih.gov/pubmed/19489992?tool=bestpractice.com 一项纳入近 900 例患者的随机对照试验发现,接受过急诊科医生简短干预的个体,其饮酒量和酒后驾驶行为均减少。[61]D'Onofrio G, Fiellin DA, Pantalon MV, et al. A brief intervention reduces hazardous and harmful drinking in emergency department patients. Ann Emerg Med. 2012 Aug;60(2):181-92.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811141/http://www.ncbi.nlm.nih.gov/pubmed/22459448?tool=bestpractice.com 在一项针对 6 项 meta 分析和 1 项系统性回顾的综述中,短期干预减少了酒精使用,特别是在存在饮酒过量的个体中。[56]Álvarez-Bueno C, Rodríguez-Martín B, García-Ortiz L, et al. Effectiveness of brief interventions in primary health care settings to decrease alcohol consumption by adult non-dependent drinkers: a systematic review of systematic reviews. Prev Med. 2015 Jul;76(suppl):S33-8.http://www.ncbi.nlm.nih.gov/pubmed/25514547?tool=bestpractice.com
动机性访谈是一种帮助患者识别并利用其自身治疗资源的技术,在促使患者参与治疗及减少成瘾性物质使用方面是有效的。[62]Miller WR, Rollnick S. Motivational interviewing: preparing people to change addictive behavior. New York, NY: Guilford Press; 1991.
一项在创伤机构开展的多点 RCT 发现,与仅接受简短动机性访谈的患者相比,辅以因人而异电话追踪的“强化”治疗的患者,在长达 12 个月时几个酒精相关指标都有改善。[63]Field C, Walters S, Marti CN, et al. A multisite randomized controlled trial of brief intervention to reduce drinking in the trauma care setting: how brief is brief? Ann Surg. 2014 May;259(5):873-80.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984362/http://www.ncbi.nlm.nih.gov/pubmed/24263324?tool=bestpractice.com
通常需要针对酒精使用进行追踪随访;可能需获取实验室检查结果,以评估酒精对身体的影响,并追踪为减少或戒掉酒精使用而作出的努力。
中重度酒精使用障碍
酒精戒断的治疗(脱毒)
中重度酒精使用障碍患者在减少或停止饮酒时会出现明显的戒断症状。临床酒精戒断状态评定量表 (CIWA-Ar) 是用来评定酒精戒断综合征 (AWS) 严重性的一种标准工具。[53]Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Br J Addict. 1989 Nov;84(11):1353-7.http://www.ncbi.nlm.nih.gov/pubmed/2597811?tool=bestpractice.comClinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA- Ar) 对于得分达到 8 至 10 分或更多的患者,需采用苯二氮卓类药物来减轻 AWS 的严重性。[37]Sullivan JT, Swift RM, Lewis DC. Benzodiazepines requirements during alcohol withdrawal syndrome: clinical implications of using standardized withdrawal scale. J Clin Psychopharmacol. 1991 Oct;11(5):291-5.http://www.ncbi.nlm.nih.gov/pubmed/1684974?tool=bestpractice.com[54]Kosten TR, O'Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003 May 1;348(18):1786-95.http://www.ncbi.nlm.nih.gov/pubmed/12724485?tool=bestpractice.com [
]What are the effects of benzodiazepines in people with alcohol withdrawal?https://cochranelibrary.com/cca/doi/10.1002/cca.493/full显示答案 [
]How do different pharmacological interventions compare for the treatment of alcohol withdrawal syndrome?https://cochranelibrary.com/cca/doi/10.1002/cca.1409/full显示答案
有酒精戒断病史且并发抽搐和/或震颤谵妄的患者需要住院治疗,存在躯体、精神和心理因素的患者也应住院接受治疗。对于无酒精戒断并发症病史或其他复杂化因素的患者,可以在能够进行药物监测的门诊机构进行脱毒治疗。不管在什么机构治疗,AWS 的总体治疗目标是促使患者参与长期家庭或门诊/强化门诊治疗方案,以帮助他们开始并维持长期持续的戒酒。[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[16]Malcolm RJ. GABA systems, benzodiazepines, and substance dependence. J Clin Psychiatry. 2003;64(suppl 3):36-40.http://www.ncbi.nlm.nih.gov/pubmed/12662132?tool=bestpractice.com[64]Ait-Daoud N, Malcolm RJ Jr, Johnson BA. An overview of medications for the treatment of alcohol withdrawal and alcohol dependence with an emphasis on the use of older and newer anticonvulsants. Addict Behav. 2006 Sep;31(9):1628-49.http://www.ncbi.nlm.nih.gov/pubmed/16472931?tool=bestpractice.com
社会心理干预
非药物治疗对该类所有患者都有用,因为它们可以为患者提供避免酒精使用的策略,增强自我效能,并减少能引起复发的应激源的影响。理想情况下,这些治疗应在必要时能随时提供躯体和精神评估以及管理和心理学支持的机构实施。
门诊和强化门诊成瘾治疗方案一般包括安排每周一次或两次到数次的治疗,治疗可延续几周至几个月(或更长)。干预措施包括认知行为治疗(帮助患者应对复饮观念和负性认知),策略建议(预防复发、应对压力、建立有益关系),以及转诊至自助小组,例如戒酒者互助会。[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[65]Powers MB, Vedel E, Emmelkamp PM. Behavioral couples therapy (BCT) for alcohol and drug use disorders: a meta-analysis. Clin Psychol Rev. 2008 Jul;28(6):952-62.http://www.ncbi.nlm.nih.gov/pubmed/18374464?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 然而,在一项包含 6 项研究的 meta 分析中,根据手册进行的认知行为疗法,联合纳曲酮治疗并未降低复发率。[67]Agosti V, Nunes EV, O'Shea D. Do manualized psychosocial interventions help reduce relapse among alcohol-dependent adults treated with naltrexone or placebo? A meta-analysis. Am J Addict. 2012 Nov-Dec;21(6):501-7.http://www.ncbi.nlm.nih.gov/pubmed/23082827?tool=bestpractice.com
1939 年创建的嗜酒者互戒协会 (AA) 是最常见的自助项目。其首要目标是帮助患者维持对酒精和其他成瘾性物质的完全戒除。Alcoholics Anonymous 像 AA 一样的自助项目可以为许多患者及其家庭提供有价值的额外支持。若患者通过参与小组获益,要鼓励他们后续更长时间内继续参与小组活动;一些患者可能从无限期的参与中获益。一项大型随机对照试验 (RCT) 发现,AA 主要通过适应性社交网络改变和社会自我效能来实现饮酒结局的改善。[68]Kelly JF, Hoeppner B, Stout RL, et al. Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis. Addiction. 2012 Feb;107(2):289-99.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242865/http://www.ncbi.nlm.nih.gov/pubmed/21917054?tool=bestpractice.com
尽管一些长期干预管理(包括病例管理、与初级保健合作、社会工作援助、增加药物和精神科治疗计划的可及性以及预防复发建议)被假设是更有效的,但与仅接受初级保健预约并转诊到物质滥用治疗的患者相比,接受长期干预管理的患者自我报告的戒酒率在 12 个月时并无明显改善。[69]Saitz R, Cheng DM, Winter M, et al. Chronic care management for dependence on alcohol and other drugs: the AHEAD randomized trial. JAMA. 2013 Sep 18;310(11):1156-67.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902022/http://www.ncbi.nlm.nih.gov/pubmed/24045740?tool=bestpractice.com
预防复发/增强戒酒:药物治疗
研究发现特定药物对减轻寻找和饮酒的冲动(“渴求”)有效。急性酒精戒断期的渴求通常是突出的,而且会在长期节制后持续存在。[10]Addolorato G, Leggio L, Abenavoli L, et al. Neurobiochemical and clinical aspects of craving in alcohol addiction: a review. Addict Behav. 2005 Jul;30(6):1209-24.http://www.ncbi.nlm.nih.gov/pubmed/15925129?tool=bestpractice.com 饮酒的冲动可导致再饮“第一杯酒”,这会导致再次出现难以控制的酒精使用。[10]Addolorato G, Leggio L, Abenavoli L, et al. Neurobiochemical and clinical aspects of craving in alcohol addiction: a review. Addict Behav. 2005 Jul;30(6):1209-24.http://www.ncbi.nlm.nih.gov/pubmed/15925129?tool=bestpractice.com 尽管抗成瘾药物对饮酒产生影响的具体机制尚未完全明确,但仍认为这类药物作用于神经递质系统,对该现象起作用。[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
虽然药物治疗显示有效,但其较少用于治疗酒精使用障碍。[73]Williams SH. Medications for treating alcohol dependence. Am Fam Physician. 2005 Nov 1;72(9):1775-80.http://www.aafp.org/afp/20051101/1775.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/16300039?tool=bestpractice.com 与单一治疗方法相比,社会心理干预联合药物治疗对酒精依赖患者的结局有更好的改善效果。[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[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 联合治疗当前被认为是酒精依赖患者的标准治疗方式。
许多药物可用于预防复发/促进戒酒:纳曲酮(口服或长效注射)、阿坎酸和双硫仑。此外,其他药物(例如托吡酯、昂丹司琼和选择性 5-羟色胺再摄取抑制剂)目前超适应症用于经选择的患者。
纳曲酮是阿片受体拮抗剂,通过减弱酒精奖赏效应和强化作用来减少酒精使用。 [
]What are the effects of opioid antagonists in people with alcohol dependence?https://cochranelibrary.com/cca/doi/10.1002/cca.601/full显示答案 具体而言,纳曲酮阻断内源性阿片对阿片受体的刺激,并减少腹侧被盖区的多巴胺释放。[74]Soyka M, Rösner S. Opioid antagonists for pharmacological treatment of alcohol dependence - a critical review. Curr Drug Abuse Rev. 2008 Nov;1(3):280-91.http://www.ncbi.nlm.nih.gov/pubmed/19630726?tool=bestpractice.com 目前发现它在具有中重度酒精使用障碍家族史的患者和有明显酒精渴求的患者中尤其有帮助。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。 新证据表明,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。 该药物可用于仍在持续饮酒的患者,通常其耐受性良好。纳曲酮可以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药物几天后才能使用该药物。尽管研究认为纳曲酮的总体效果比较轻微,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 来自 meta 回归分析的一些证据表明,与较轻度的饮酒者相比,酒精依赖更严重的患者能更多的获益于纳曲酮。[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
纳曲酮(长效注射剂)适用于以下患者:更愿意采用每月给药一次这一便捷方式的患者,既往服药依从性差的患者,以及生活环境不允许规律服药的患者(例如无家可归者)。[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 据报道口服纳曲酮可引起肝损伤,与此不同,长效制剂对当前饮酒的酒依赖患者并未表现出肝脏毒性。[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 因此,在减少酒精使用和增加戒酒方面,纳曲酮的长效制剂可能对酒依赖更严重的患者尤其有用。[85]Pettinati HM, Silverman BL, Battisti JJ, et al. Efficacy of extended-release naltrexone in patients with relatively higher severity of alcohol dependence. Alcohol Clin Exp Res. 2011 Oct;35(10):1804-11.http://www.ncbi.nlm.nih.gov/pubmed/21575016?tool=bestpractice.com
阿坎酸是一种使中枢神经系统内谷氨酸和 γ-氨基丁酸神经递质系统恢复正常的药品。这些反应被认为能减少戒酒相关的持续症状(例如焦虑、失眠)和成瘾。一项系统评价发现,对于已经停止饮酒的酒精使用障碍患者,使用阿坎酸联合社会心理行为治疗可有效促进戒酒。[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。一项纳入 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、改善治疗完成率以及提高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
双硫仑通过抑制乙醛脱氢酶来阻断酒精的代谢途径,从而增加饮酒后乙醛的水平。这种双硫仑-酒精反应会产生一些躯体影响:血管舒张症状(面色潮红)、心血管症状(心动过速、低血压)、消化系统症状(恶心、呕吐、腹泻)、头痛、呼吸抑制和乏力。这些症状通常短暂出现,但可能出现严重反应,这种情况下需要及时药物治疗。对于主动打算戒酒的患者可开具双硫仑,通过负性强化来促进戒酒。通常情况下,每日常规服用双硫仑的患者将不会饮酒,以避免乙醛积聚引起不适的生理学反应。然而,在许多患者中,对每日双硫仑的治疗依从性差往往会限制临床疗效,使用该药时需要考虑潜在的肝毒性。通过配偶或伙伴监督服用双硫仑会增加治疗成功率。
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 纳美芬应当在酒精使用障碍患者担心他们可能会饮酒的当天使用,最好是饮酒前 1-2 小时(但如果已开始饮酒,则越快越好)。美国市场已没有该药,其有效性因临床试验的方法学缺陷而受到质疑。[89]Palpacuer C, Laviolle B, Boussageon R, et al. Risks and benefits of nalmefene in the treatment of adult alcohol dependence: a systematic literature review and meta-analysis of published and unpublished double-blind randomized controlled trials. PLoS Med. 2015 Dec 22;12(12):e1001924.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687857/http://www.ncbi.nlm.nih.gov/pubmed/26694529?tool=bestpractice.com
目前还没有足够的证据支持我们推荐某一特定的药物治疗。一项美国的大型试验(COMBIONE 项目)发现联合使用阿坎酸和纳曲酮并无获益。[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 [
]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 如果预防复饮药物能使患者更加努力维持戒酒,应当持续使用数周至数月,甚至更长时间。研究发现,纳曲酮(口服)和阿坎酸在 12 至 16 周显现出阳性结果。注射用纳曲酮治疗在 6 个月的时间范围内显示出获益。相关研究并未明确使用这些药物的严格时间间隔,采用灵活的用药方法是合理的。英国国家卫生与临床优化研究所的建议指出,对于能从治疗中获益并且愿意继续治疗的患者,可使用纳曲酮或阿坎酸治疗长达 6 个月或更长时间。[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
服药不依从是使用抗渴求药物效果差的明显影响因素。如果怀疑患者服药依从性差,找出不依从的原因,并帮助患者制定计划来解决这些问题非常重要。COMBINE 项目的药物管理治疗手册提供了一份关于处理不依从性策略的总结。[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[90]Pettinati HM, Weiss RD, Miller, WR, et al. COMBINE monograph series, volume 2. Medical management treatment manual: a clinical research guide for medically trained clinicians providing pharmacotherapy as part of the treatment for alcohol dependence. Bethesda, MD: NIAAA; 2004.http://pubs.niaaa.nih.gov/publications/combine/Combine%202.pdfProject COMBINE medical management treatment manual: a clinical research guide for medically trained clinicians providing pharmacotherapy as part of the treatment for alcohol dependence
治疗方式的整合
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
妊娠女性
目前为止,尚无随机临床试验在接受酒精治疗方案的妊娠女性中评估药物治疗对改善母亲、生产和婴儿结局的作用。[94]Smith EJ, Lui S, Terplan M. Pharmacologic interventions for pregnant women enrolled in alcohol treatment. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007361.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD007361.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19588428?tool=bestpractice.com
青少年
一项包含16 项研究的 meta 分析发现干预措施对减少青少年酒精使用是有效的,个体导向的治疗可能比以家庭为基础的方式有更大的效果。效果较好的干预措施包括简短动机性访谈、含12 步方法的认知行为治疗、出院后的认知行为治疗、多维度的家庭治疗、对青少年的简短干预以及对青少年及其父母的简短干预。[95]Tripodi SJ, Bender K, Litschge C, et al. Interventions for reducing adolescent alcohol abuse: a meta-analytic review. Arch Pediatr Adolesc Med. 2010 Jan;164(1):85-91.http://archpedi.ama-assn.org/cgi/content/full/164/1/85http://www.ncbi.nlm.nih.gov/pubmed/20048247?tool=bestpractice.com 尽管以团体治疗为基础的治疗方式对青少年可能有效,但需要进一步研究证实。[96]Engle B, Macgowan MJ. A critical review of adolescent substance abuse group treatments. J Evid Based Soc Work. 2009 Jul;6(3):217-43.http://www.ncbi.nlm.nih.gov/pubmed/20183675?tool=bestpractice.com 青少年酒精使用面对的另一个问题是酒精产品的广告,会导致青少年出现酒精使用的可能性增加。[97]Anderson P. Is it time to ban alcohol advertising? Clin Med (Lond). 2009 Apr;9(2):121-4.http://www.ncbi.nlm.nih.gov/pubmed/19435114?tool=bestpractice.com