在焦虑、心境和物质相关障碍中,患者经常有惊恐发作,并不需要特定治疗。 惊恐障碍经常出现于初级医疗保健机构中,如果未被查出并给予足够治疗,则大大浪费了医疗资源和费用。[9]Roy-Byrne PP, Wagner AW, Schraufnagel TJ. Understanding and treating panic disorder in the primary care setting. J Clin Psychiatry. 2005;66 Suppl 4:16-22.http://www.ncbi.nlm.nih.gov/pubmed/15842183?tool=bestpractice.com[50]Barsky AJ, Delamater BA, Orav JE. Panic disorder patients and their medical care. Psychosomatics. 1999 Jan-Feb;40(1):50-6.http://www.ncbi.nlm.nih.gov/pubmed/9989121?tool=bestpractice.com 治疗的主要目标是降低惊恐发作的强度、频率和持续时间,减少回避行为,限制对安全线索的过分依赖,改善功能。治疗方法应该考虑既往治疗史、患者偏好、共病障碍和治疗的可获得性。由于复发率高,因此在停用药物治疗前,应该确保患者获得了最大的功能恢复。[51]Doyle A, Pollack MH. Long-term management of panic disorder. J Clin Psychiatry. 2004;65 Suppl 5:24-8.http://www.ncbi.nlm.nih.gov/pubmed/15078115?tool=bestpractice.com[52]Cloos JM. The treatment of panic disorder. Curr Opin Psychiatry. 2005 Jan;18(1):45-50.http://www.ncbi.nlm.nih.gov/pubmed/16639183?tool=bestpractice.com 如果患者对于初始治疗未产生足够反应,可能需将其转诊给精神专科医生进行额外的药物治疗,或者转诊给擅长惊恐障碍行为认知疗法的心理健康专业人员。治疗可能还需要家庭成员参与,以帮助患者尽可能多地参与推荐的干预措施。随着时间推移,为避免复发,应该常规监测患者的功能状态和回避行为。
为了帮助确保症状减少和预防复发,药物治疗从起效开始至少持续使用 1 年。一项针对 28 项研究的系统评价和 Meta 分析结果显示,对抗抑郁药物治疗有效的焦虑症(包括惊恐障碍)患者中,至少一年的治疗可以降低复发率,且耐受性良好。由于纳入 Meta 分析的研究只有最长一年的治疗时间,因此没有证据表明超过该时间治疗的有效性和耐受性;然而,这段时间后缺乏证据不应被理解为明确建议在一年后停止服用抗抑郁药物。[53]Batelaan NM, Bosman RC, Muntingh A, et al. Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials. BMJ. 2017 Sep 13;358:j3927.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596392/http://www.ncbi.nlm.nih.gov/pubmed/28903922?tool=bestpractice.com 如果决定减药,要评估目前药物疗效的优势和劣势,讨论症状稳定的持续时间,以及可能影响复发的预测因素和问题解决办法。[54]American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder, second edition. 2009 [internet publication].http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/panicdisorder.pdf 推荐缓慢、逐渐减量,并要经常监测治疗反应。
协作治疗是治疗焦虑障碍的一种有效方法,涉及在初级医疗保健机构中将循证认知行为疗法 (cognitive behavioural therapy, CBT) 和药物治疗进行整合。协同焦虑学习和管理 (Coordinated Anxiety Learning and Management, CALM) 研究是一项大规模、多中心随机对照试验,该研究显示循证干预(如 CBT 和/或药物治疗)能够显著减轻初级医疗保健机构中焦虑障碍患者的症状和功能障碍,并改善生活质量。[55]Roy-Byrne P, Craske MG, Sullivan G, et al. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. JAMA. 2010 May 19;303(19):1921-8.http://www.ncbi.nlm.nih.gov/pubmed/20483968?tool=bestpractice.com[56]Sullivan G, Craske MG, Sherbourne C, et al. Design of the Coordinated Anxiety Learning and Management (CALM) study: innovations in collaborative care for anxiety disorders. Gen Hosp Psychiatry. 2007 Sep-Oct;29(5):379-87.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095116/http://www.ncbi.nlm.nih.gov/pubmed/17888803?tool=bestpractice.com 惊恐障碍患者在6个月和12个月随访时,CALM组明显优于常规治疗组。[57]Craske MG, Stein MB, Sullivan G, et al. Disorder-specific impact of coordinated anxiety learning and management treatment for anxiety disorders in primary care. Arch Gen Psychiatry. 2011 Apr;68(4):378-88.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074172/http://www.ncbi.nlm.nih.gov/pubmed/21464362?tool=bestpractice.com 类似地,研究发现使用基于电话的协同治疗以及具有分步治疗选择的计算机化 CBT 优于常规治疗。[58]Rollman BL, Belnap BH, Mazumdar S, et al. Telephone-delivered stepped collaborative care for treating anxiety in primary care: a randomized controlled trial. J Gen Intern Med. 2017 Mar;32(3):245-55.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330997/http://www.ncbi.nlm.nih.gov/pubmed/27714649?tool=bestpractice.com[59]Rollman BL, Herbeck Belnap B, Abebe KZ, et al. Effectiveness of online collaborative care for treating mood and anxiety disorders in primary care: a randomized clinical trial. JAMA Psychiatry. 2018 Jan 1;75(1):56-64.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833533/http://www.ncbi.nlm.nih.gov/pubmed/29117275?tool=bestpractice.com
一项关于随访研究的大型 Meta 分析比较了治疗停止后 24 个月期间不同焦虑障碍(包括惊恐障碍)治疗的持久效果。结果发现,随着时间推移,使用 CBT 治疗患者的症状得到了显著改善,而药物治疗组患者在停止治疗后的阶段症状则保持稳定。安慰剂组患者随着时间推移未出现症状恶化,但确实显示出比使用 CBT 治疗患者明显更劣的结局。[60]Bandelow B, Sagebiel A, Belz M, et al. Enduring effects of psychological treatments for anxiety disorders: meta-analysis of follow-up studies. Br J Psychiatry. 2018 Jun;212(6):333-8.http://www.ncbi.nlm.nih.gov/pubmed/29706139?tool=bestpractice.com
有关惊恐和焦虑性质的教育和信息
任何治疗方法的关键部分均为关于惊恐和焦虑性质的信息和教育。尤其值得一提的是,惊恐是对所感知到的危险作出的可理解反应(“战斗或逃跑”反应)。惊恐发作虽然不适,但并不危险。恐惧源自对正常躯体感觉的误解。与患者一起画一张简单的图(用箭头将症状、解释、焦虑连起来,形成一个“恶性循环”)可能会有帮助。患者务必要意识到治疗的首要目标并不是消除所有焦虑,而是成功管理焦虑。患者为应对焦虑而进行的尝试(例如逃避或寻求安全感)是可以理解的,但会不经意地导致问题持续存在。
不是惊恐障碍的惊恐发作
如果患者出现急性惊恐发作,应使患者安心,告知患者症状不危险,并且发作很快就会消退。急性发作时,通常会出现过度换气,但患者主观认为是气短。这些问题应该跟患者进行解释,并重点强调减缓呼吸。利用安静的房间和获取其他重要人物的支持,有助于治疗。在急诊时,可考虑给予苯二氮䓬类药物终止急性发作。
对于首次发作的患者,应该告诉患者这种发作很常见,多达1/3的人一生中会经历。 但是发展成真正的惊恐障碍不到10%。 虽然发作很不舒服,但并不危险,并且发作时间是有限的。
对于亚临床症状,无需特定治疗。 虽然经常使用普萘洛尔治疗惊恐相关症状,但安慰剂对照研究并未发现普萘洛尔治疗有效的证据。[61]Munjack DJ, Crocker B, Cabe D, et al. Alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. J Clin Psychopharmacol. 1989 Feb;9(1):22-7.http://www.ncbi.nlm.nih.gov/pubmed/2651490?tool=bestpractice.com 基于 CBT 原则的自我帮助材料是有益的。症状改善:质量较差的证据显示,与不治疗相比,自助可以改善症状。[62]Kumar S, Malone D. Panic disorder. BMJ Clin Evid. 2008 Dec 16;2008.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907935/http://www.ncbi.nlm.nih.gov/pubmed/19445787?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)。 单独提供给患者书面材料或与简短的电话交流联合使用,都有助于降低惊恐相关的症状。[63]Sharp DM, Power KG, Swanson V. Reducing therapist contact in cognitive behaviour therapy for panic disorder and agoraphobia in primary care: global measures of outcome in a randomised controlled trial. Br J Gen Pract. 2000 Dec;50(461):963-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1313882/http://www.ncbi.nlm.nih.gov/pubmed/11224967?tool=bestpractice.com[64]Febbraro GA. An investigation into the effectiveness of bibliotherapy and minimal contact interventions in the treatment of panic attacks. J Clin Psychol. 2005 Jun;61(6):763-79.http://www.ncbi.nlm.nih.gov/pubmed/15546141?tool=bestpractice.com 当与能够监测治疗反应的专业人员联合使用时,阅读疗法的效果会更好。[65]Febbraro GA, Clum GA, Roodman AA, et al. The limits of bibliotherapy: a study of the differential effectiveness of self-administered interventions in individuals with panic attacks. Beh Ther. 1999;30(2):209-22.[66]The Reading Agency (UK). Reading Well Books on Prescription scheme. 2018 [internet publication].http://readingagency.org.uk/adults/quick-guides/reading-well/#reading-well-books-on-prescription 尽管治疗师给予的治疗看起来优于自助干预,但自助干预也有很好的疗效。[67]Lewis C, Pearce J, Bisson JI. Efficacy, cost-effectiveness and acceptability of self-help interventions for anxiety disorders: systematic review. Br J Psychiatry. 2012 Jan;200(1):15-21.http://www.ncbi.nlm.nih.gov/pubmed/22215865?tool=bestpractice.com 自助干预的优点是费用低、易获得、易于操作和方便。 但由于是普通的治疗方法,缺乏责任性,理解和正确执行治疗原则可能存在困难。
惊恐发作也很常见于其他焦虑障碍、心境障碍和物质使用障碍。因此,建议对上述这些障碍进行补充筛查。
应该鼓励患者监测惊恐发作的强度、频率和持续时间,发作是否可预料。 须在2周内进行随访评价或电话检查,再次评估患者的症状。
不伴共病的惊恐障碍
有证据表明,自助、CBT 和选择性 5-羟色胺再摄取抑制剂 (SSRI)/5-羟色胺-去甲肾上腺素再摄取抑制剂 (SNRI) 药物是具有同等疗效的一线治疗,具体取决于个人意愿。[68]Andrisano C, Chiesa A, Serretti A. Newer antidepressants and panic disorder: a meta-analysis. Int Clin Psychopharmacol. 2013 Jan;28(1):33-45.http://www.ncbi.nlm.nih.gov/pubmed/23111544?tool=bestpractice.com[69]National Institute for Health and Care Excellence. Generalised anxiety disorder and panic disorder in adults: management. Jan 2011 [internet publication].http://www.nice.org.uk/guidance/CG113症状改善:质量较差的证据显示,与抗抑郁剂相比,CBT是否可以改善症状尚不清楚。[62]Kumar S, Malone D. Panic disorder. BMJ Clin Evid. 2008 Dec 16;2008.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907935/http://www.ncbi.nlm.nih.gov/pubmed/19445787?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)。 CBT 可以单独使用,或作为任何形式药物疗法的附加治疗。[70]Hofmann SG, Sawyer AT, Korte KJ, et al. Is it beneficial to add pharmacotherapy to cognitive-behavioral therapy when treating anxiety disorders? A meta-analytic review. Int J Cogn Ther. 2009 Jan 1;2(2):160-75.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732196/http://www.ncbi.nlm.nih.gov/pubmed/19714228?tool=bestpractice.com
三环类抗抑郁药 (TCA) 为二线选择(如丙米嗪或氯米帕明)。苯二氮䓬类药物可用于以下情况:特定用于处理短期焦虑危机时,在耐药性惊恐障碍患者的治疗中用作 SSRI、SNRI 和 TCA 的辅助增加药物,或者为了预防由抗抑郁药物副作用所致症状恶化,而在抗抑郁治疗开始阶段使用。如果初始治疗疗效欠佳,应促使重新考虑诊断或者是否存在其他焦虑障碍、心境障碍或物质障碍等共病。
SSRI/SNRI:
惊恐障碍治疗的一线药物。[9]Roy-Byrne PP, Wagner AW, Schraufnagel TJ. Understanding and treating panic disorder in the primary care setting. J Clin Psychiatry. 2005;66 Suppl 4:16-22.http://www.ncbi.nlm.nih.gov/pubmed/15842183?tool=bestpractice.com[18]Roy-Byrne PP, Craske MG, Stein M. Panic disorder. Lancet. 2006 Sep 16;368(9540):1023-32.http://www.ncbi.nlm.nih.gov/pubmed/16980119?tool=bestpractice.com[71]Bakker A, van Balkom AJ, Stein DJ. Evidence-based pharmacotherapy of panic disorder. Int J Neuropsychopharmacol. 2005 Sep;8(3):473-82.http://www.ncbi.nlm.nih.gov/pubmed/15804373?tool=bestpractice.com[72]Bradwejn J, Ahokas A, Stein DJ, et al. Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study. Br J Psychiatry. 2005 Oct;187:352-9.http://bjp.rcpsych.org/content/187/4/352.fullhttp://www.ncbi.nlm.nih.gov/pubmed/16199795?tool=bestpractice.com[73]Batelaan NM, Van Balkom AJ, Stein DJ. Evidence-based pharmacotherapy of panic disorder: an update. Int J Neuropsychopharmacol. 2012 Apr;15(3):403-15.https://academic.oup.com/ijnp/article/15/3/403/721159http://www.ncbi.nlm.nih.gov/pubmed/21733234?tool=bestpractice.com[74]Freire RC, Hallak JE, Crippa JA, et al. New treatment options for panic disorder: clinical trials from 2000 to 2010. Expert Opin Pharmacother. 2011 Jun;12(9):1419-28.http://www.ncbi.nlm.nih.gov/pubmed/21342080?tool=bestpractice.com症状改善:质量较差的证据显示,与安慰剂相比,SSRI能够改善症状。[62]Kumar S, Malone D. Panic disorder. BMJ Clin Evid. 2008 Dec 16;2008.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907935/http://www.ncbi.nlm.nih.gov/pubmed/19445787?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)。
对各种其他症状(如睡眠紊乱)的治疗也有效,对经常共同存在的其他类型焦虑障碍和心境障碍也有效。[75]Roy-Byrne PP, Cowley DS. Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia, and social anxiety disorder. In: Nathan P, Gorman JM, eds. A guide to treatments that work. 3rd ed. New York, NY: Oxford University Press; 2007:337-66.
帕罗西汀、[76]Ballenger JC, Davidson JR, Lecrubier Y, et al. Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry. 1998;59 Suppl 8:47-54.http://www.ncbi.nlm.nih.gov/pubmed/9707162?tool=bestpractice.com 应考虑将应用舍曲林、[77]Pollack MH, Otto MW, Worthington JJ, et al. Sertraline in the treatment of panic disorder: a flexible-dose multicenter trial. Arch Gen Psychiatry. 1998 Nov;55(11):1010-6.http://archpsyc.jamanetwork.com/article.aspx?articleid=204431http://www.ncbi.nlm.nih.gov/pubmed/9819070?tool=bestpractice.com 氟西汀[78]Michelson D, Allgulander C, Dantendorfer K, et al. Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomized, placebo-controlled trial. Br J Psychiatry. 2001 Dec;179:514-8.http://bjp.rcpsych.org/content/179/6/514.fullhttp://www.ncbi.nlm.nih.gov/pubmed/11731354?tool=bestpractice.com 氟伏沙明、[79]Backish D, Hooper CL, Filteau MJ, et al. A double-blind placebo-controlled trial comparing fluvoxamine and imiprimine in the treatment of panic disorder with or without agoraphobia. Psychopharmacol Bull. 1996;32(1):135-41.http://www.ncbi.nlm.nih.gov/pubmed/8927663?tool=bestpractice.com 西酞普兰、[80]Leinonen E, Lepola U, Koponen H, et al. Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial. J Psychiatry Neurosci. 2000 Jan;25(1):24-32.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1407706/http://www.ncbi.nlm.nih.gov/pubmed/10721681?tool=bestpractice.com 艾司西酞普兰、[81]Stahl SM, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2003 Nov;64(11):1322-7.http://www.ncbi.nlm.nih.gov/pubmed/14658946?tool=bestpractice.com 以及文拉法辛。[72]Bradwejn J, Ahokas A, Stein DJ, et al. Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study. Br J Psychiatry. 2005 Oct;187:352-9.http://bjp.rcpsych.org/content/187/4/352.fullhttp://www.ncbi.nlm.nih.gov/pubmed/16199795?tool=bestpractice.com 均显示出了有效性,且有效性的出现延迟(2-12 周)。[75]Roy-Byrne PP, Cowley DS. Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia, and social anxiety disorder. In: Nathan P, Gorman JM, eds. A guide to treatments that work. 3rd ed. New York, NY: Oxford University Press; 2007:337-66.[82]Mochcovitch MD, Nardi AE. Selective serotonin-reuptake inhibitors in the treatment of panic disorder: a systematic review of placebo-controlled studies. Expert Rev Neurother. 2010 Aug;10(8):1285-93.http://www.ncbi.nlm.nih.gov/pubmed/20662754?tool=bestpractice.com
抗抑郁剂的选择取决于是否可以获得、不良反应、戒断症状风险(如头晕、易激惹、恶心和焦虑加重)和滴定的简便性。 帕罗西汀和文拉法辛的戒断症状风险高于氟西汀。
CBT:
CBT是一种限定时间、需要技术的、有效的一线治疗。这种治疗的设计原理是改变那些维持或加重患者症状或功能损害的想法、行为和对环境突发事件的处理。[83]Barlow DH, Gorman JM, Shear MK, et al. Cognitive-behavioral therapy, imiprimine, or their combination for panic disorder: a randomized controlled trial. JAMA. 2000 May 17;283(19):2529-36.http://jama.jamanetwork.com/article.aspx?articleid=192707http://www.ncbi.nlm.nih.gov/pubmed/10815116?tool=bestpractice.com[84]Otto MW, Deveney C. Cognitive-behavioral therapy and the treatment of panic disorder: efficacy and strategies. J Clin Psychiatry. 2005;66 Suppl 4:28-32.http://www.ncbi.nlm.nih.gov/pubmed/15842185?tool=bestpractice.com[85]Sánchez-Meca J, Rosa-Alcázar AI, Marín-Martínez F, et al. Psychological treatment of panic disorder with or without agoraphobia: a meta-analysis. Clin Psychol Rev. 2010 Feb;30(1):37-50.http://www.ncbi.nlm.nih.gov/pubmed/19775792?tool=bestpractice.com [
]What are the benefits and harms of psychological therapies in adults with panic disorder?https://cochranelibrary.com/cca/doi/10.1002/cca.1378/full显示答案 虽然有报道6~7次的CBT治疗也有效,但通常治疗次数为12~14次。[86]Marchand A, Roberge P, Primiano S, et al. A randomized, controlled clinical trial of standard, group and brief cognitive-behavioral therapy for panic disorder with agoraphobia: a two-year follow-up. J Anxiety Disord. 2009 Dec;23(8):1139-47.http://www.ncbi.nlm.nih.gov/pubmed/19709851?tool=bestpractice.com 建议将患者转诊给擅长 CBT 的精神卫生专业人员。转诊医生和精神卫生专业人员应保持定期合作。证据还显示出在初级医疗保健机构采用协作治疗的有益作用,包括使用计算机化 CBT 和协调治疗方案。[55]Roy-Byrne P, Craske MG, Sullivan G, et al. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. JAMA. 2010 May 19;303(19):1921-8.http://www.ncbi.nlm.nih.gov/pubmed/20483968?tool=bestpractice.com[58]Rollman BL, Belnap BH, Mazumdar S, et al. Telephone-delivered stepped collaborative care for treating anxiety in primary care: a randomized controlled trial. J Gen Intern Med. 2017 Mar;32(3):245-55.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330997/http://www.ncbi.nlm.nih.gov/pubmed/27714649?tool=bestpractice.com[59]Rollman BL, Herbeck Belnap B, Abebe KZ, et al. Effectiveness of online collaborative care for treating mood and anxiety disorders in primary care: a randomized clinical trial. JAMA Psychiatry. 2018 Jan 1;75(1):56-64.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833533/http://www.ncbi.nlm.nih.gov/pubmed/29117275?tool=bestpractice.com[87]Roy-Byrne PP, Craske MG, Stein MB, et al. A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. Arch Gen Psychiatry. 2005 Mar;62(3):290-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1237029/http://www.ncbi.nlm.nih.gov/pubmed/15753242?tool=bestpractice.com
针对惊恐的认知行为疗法的目标是让患者在体验惊恐症状时不感到害怕,并且消除对逃避和安全感寻求的依赖,以便使患者了解到在惊恐发作期间,实际上不会发生任何危险。 为了学习如何自我管理并克服惊恐,可能需要通过以可预测、可控的方式直面恐惧的感觉和情境来暂时增加焦虑。
用于治疗惊恐障碍的 CBT 涉及教育、自我监控、放松训练(包括呼吸再训练)、挑战消极思维方式、情境暴露训练以及系统性暴露于令人不适的身体感觉等联合治疗。后者涉及同时暴露于内在身体感觉(如同“行为实验”)和外部诱发因素(如果个体还存在广场恐怖症)。以逐渐、重复、可控的方式暴露于相关的不适身体感觉(如头晕、换气过度和心动过速),能够随着时间的推移,减少恐惧的想法,并增加对这些感觉的耐受性。例如,患者和治疗师可以一起过度呼吸,以表明这种行为不会导致意识丧失,或者他们可以约定好,在一个炎热的房间里进行运动,以证明心跳加速不会导致心脏病发作。外部分级暴露涉及不依赖于安全线索(如配偶、药物治疗),逐渐增加患者对之前逃避情境(如人群、商店、队列、公共交通)的耐受力。反复、经常、可控、可预测的暴露能够获得最佳疗效。某些活动(如锻炼或喝咖啡)在暴露治疗的早期应该避免,因为它们诱发的躯体感觉与惊恐发作时的类似,但这些活动可以融入到治疗后期的暴露等级中。
基于 CBT 原则的自我帮助材料是有益的。症状改善:质量较差的证据显示,与不治疗相比,自助可以改善症状。[62]Kumar S, Malone D. Panic disorder. BMJ Clin Evid. 2008 Dec 16;2008.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907935/http://www.ncbi.nlm.nih.gov/pubmed/19445787?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)。 阅读疗法无论单用还是和简短的电话交流联合使用,都有助于惊恐症状的减轻。[63]Sharp DM, Power KG, Swanson V. Reducing therapist contact in cognitive behaviour therapy for panic disorder and agoraphobia in primary care: global measures of outcome in a randomised controlled trial. Br J Gen Pract. 2000 Dec;50(461):963-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1313882/http://www.ncbi.nlm.nih.gov/pubmed/11224967?tool=bestpractice.com[88]Febbraro GA. An investigation into the effectiveness of bibliotherapy and minimal contact interventions in the treatment of panic attacks. J Clin Psychol. 2005 Jun;61(6):763-79.http://www.ncbi.nlm.nih.gov/pubmed/15546141?tool=bestpractice.com 尽管治疗师给予的治疗看起来优于自助干预,但自助干预也有很好的疗效。[67]Lewis C, Pearce J, Bisson JI. Efficacy, cost-effectiveness and acceptability of self-help interventions for anxiety disorders: systematic review. Br J Psychiatry. 2012 Jan;200(1):15-21.http://www.ncbi.nlm.nih.gov/pubmed/22215865?tool=bestpractice.com 与无治疗师辅助的自我指导的暴露相比,治疗师辅助的暴露更能减少场所回避和惊恐程度。[89]Gloster AT, Wittchen HU, Einsle F, et al. Psychological treatment for panic disorder with agoraphobia: a randomized controlled trial to examine the role of therapist-guided exposure in situ in CBT. J Consult Clin Psychol. 2011 Jun;79(3):406-20.http://www.ncbi.nlm.nih.gov/pubmed/21534651?tool=bestpractice.com 当与能够监测治疗反应的专业人员联合使用时,阅读疗法的效果会更好。[65]Febbraro GA, Clum GA, Roodman AA, et al. The limits of bibliotherapy: a study of the differential effectiveness of self-administered interventions in individuals with panic attacks. Beh Ther. 1999;30(2):209-22. 自助干预的优点是费用低、易获得、易于操作和方便。 但由于是普通的治疗方法,缺乏责任性,理解和正确执行治疗原则可能存在困难。
CBT 联合药物治疗可能提高药物依从性、增加有效率,并减少控制症状所需使用的药物剂量。[83]Barlow DH, Gorman JM, Shear MK, et al. Cognitive-behavioral therapy, imiprimine, or their combination for panic disorder: a randomized controlled trial. JAMA. 2000 May 17;283(19):2529-36.http://jama.jamanetwork.com/article.aspx?articleid=192707http://www.ncbi.nlm.nih.gov/pubmed/10815116?tool=bestpractice.com[87]Roy-Byrne PP, Craske MG, Stein MB, et al. A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. Arch Gen Psychiatry. 2005 Mar;62(3):290-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1237029/http://www.ncbi.nlm.nih.gov/pubmed/15753242?tool=bestpractice.com[90]de Beurs E, van Balkom AJ, Lange A, et al. Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone. Am J Psychiatry. 1995 May;152(5):683-91.http://www.ncbi.nlm.nih.gov/pubmed/7726307?tool=bestpractice.com[91]van Apeldoorn FJ, van Hout WJ, Mersch PP, et al. Is a combined therapy more effective than either CBT or SSRI alone? Results of a multicenter trial on panic disorder with or without agoraphobia. Acta Psychiatr Scand. 2008 Apr;117(4):260-70.http://www.ncbi.nlm.nih.gov/pubmed/18307586?tool=bestpractice.com[92]Rosenbaum JF, Fredman SJ, Pollack MH. The pharmacotherapy of panic disorder. In: Rosenbaum JF, Pollack MH, eds. Panic disorder and its treatment. New York, NY: Marcel Dekker Inc.; 1998:153-80.[93]Furukawa TA, Watanabe N, Churchill R. Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: systematic review. Br J Psychiatry. 2006 Apr;188:305-12.http://www.ncbi.nlm.nih.gov/pubmed/16582055?tool=bestpractice.com[94]Bandelow B, Seidler-Brandler U, Becker A, et al. Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders. World J Biol Psychiatry. 2007;8(3):175-87.http://www.ncbi.nlm.nih.gov/pubmed/17654408?tool=bestpractice.com[95]Furukawa TA, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004364.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004364.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17253502?tool=bestpractice.com症状改善:质量较差的证据显示,与单用抗抑郁剂相比,认知行为治疗联合抗抑郁剂能够改善症状。[62]Kumar S, Malone D. Panic disorder. BMJ Clin Evid. 2008 Dec 16;2008.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907935/http://www.ncbi.nlm.nih.gov/pubmed/19445787?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)。 联合CBT治疗对于患者停止使用苯二氮卓类药物尤其有帮助。[96]Otto MW, Pollack MH, Sachs GS, et al. Discontinuation of benzodiazepine treatment: efficacy of cognitive-behavioral therapy for patients with panic disorder. Am J Psychiatry. 1993 Oct;150(10):1485-90.http://www.ncbi.nlm.nih.gov/pubmed/8379551?tool=bestpractice.com[97]Spiegel DA, Bruce TJ. Benzodiazepines and exposure-based cognitive-behavior therapies for panic disorder: conclusions from combined treatment trials. Am J Psychiatry. 1997 Jun;154(6):773-81.http://www.ncbi.nlm.nih.gov/pubmed/9167504?tool=bestpractice.com
苯二氮䓬类药物:
苯二氮䓬类药物可用于以下情况:特定用于处理短期焦虑危机时,在耐药性惊恐障碍患者的治疗中用作 SSRI、SNRI 和 TCA 的辅助增加药物,或者为了预防由抗抑郁药物副作用所致症状恶化,而在抗抑郁治疗开始阶段使用。推荐的苯二氮䓬类药物的最长治疗时间为 2-4 周。
英国国家卫生与临床优化研究所指南不推荐将苯二氮䓬类药物作为单药治疗选择。[69]National Institute for Health and Care Excellence. Generalised anxiety disorder and panic disorder in adults: management. Jan 2011 [internet publication].http://www.nice.org.uk/guidance/CG113
所有苯二氮䓬类药物均有耐受性、依赖性和滥用的可能。对于短效制剂,可能需考虑额外风险,并且没有额外获益。[98]Moylan S, Giorlando F, Nordfjærn T, et al. The role of alprazolam for the treatment of panic disorder in Australia. Aust N Z J Psychiatry. 2012 Mar;46(3):212-24.http://www.ncbi.nlm.nih.gov/pubmed/22391278?tool=bestpractice.com[99]Moylan S, Staples J, Ward SA, et al. The efficacy and safety of alprazolam versus other benzodiazepines in the treatment of panic disorder. J Clin Psychopharmacol. 2011 Oct;31(5):647-52.http://www.ncbi.nlm.nih.gov/pubmed/21869686?tool=bestpractice.com 如果需要使用苯二氮䓬类药物,最好规定好时间,使用较长效制剂,这样药物的使用取决于时间,而不是取决于反应/惊恐症状。 “按需使用”短效苯二氮䓬类药物,可能会导致患者对这些药物产生心理依赖。这会削弱患者产生控制症状的内在动力的能力。
苯二氮䓬类药物快速起效,总体耐受性良好。使用仅2-4周即可产生躯体依赖。突然停药或快速加量会增加戒断症状发生的风险(如头晕、易激惹、恶心、出汗、震颤、焦虑加重和痫样发作)。长效制剂(如氯硝西泮)可能是减轻剂量调整时焦虑加重的更好选择。
在没有物质滥用史的患者中,病程较长的患者谨慎使用苯二氮䓬类药物是安全的,[75]Roy-Byrne PP, Cowley DS. Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia, and social anxiety disorder. In: Nathan P, Gorman JM, eds. A guide to treatments that work. 3rd ed. New York, NY: Oxford University Press; 2007:337-66. 没有一致性证据表明随着时间推移出现滥用或剂量增加。[100]Nagy LM, Krystal JH, Woods SW, et al. Clinical and medication outcome after short-term alprazolam and behavioral group treatment in panic disorder: 2.5 year naturalistic follow-up study. Arch Gen Psychiatry. 1989 Nov;46(11):993-9.http://www.ncbi.nlm.nih.gov/pubmed/2818144?tool=bestpractice.com[101]Worthington JJ 3rd, Pollack MH, Otto MW, et al. Long-term experience with clonazepam in patients with a primary diagnosis of panic disorder. Psychopharmacol Bull. 1998;34(2):199-205.http://www.ncbi.nlm.nih.gov/pubmed/9641001?tool=bestpractice.com 使用最高日平均剂量(通常高于指南推荐的剂量)的患者,更容易出现物质滥用、共病诊断和同时使用处方精神药物,提示需要更复杂的治疗方案。[102]Hermos JA, Young MM, Lawler EV, et al. Characterizations of long-term anxiolytic benzodiazepine prescriptions in veteran patients. J Clin Psychopharmacol. 2005 Dec;25(6):600-4.http://www.ncbi.nlm.nih.gov/pubmed/16282847?tool=bestpractice.com[103]Hermos JA, Young MM, Lawler EV, et al. Long-term, high-dose benzodiazepine prescriptions in veteran patients with PTSD: influence of preexisting alcoholism and drug-abuse diagnoses. J Trauma Stress. 2007 Oct;20(5):909-14.http://www.ncbi.nlm.nih.gov/pubmed/17955537?tool=bestpractice.com
TCA:
TCA 适用于使用一种或多种 SSRI 无效或有神经病理性疼痛的患者。症状改善:质量较差的证据显示,与安慰剂相比,TCA能够改善症状。[62]Kumar S, Malone D. Panic disorder. BMJ Clin Evid. 2008 Dec 16;2008.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907935/http://www.ncbi.nlm.nih.gov/pubmed/19445787?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)。 伴有疼痛主诉的焦虑患者也可能适于应用TCA。[104]Means-Christensen AJ, Roy-Byrne PP, Sherbourne CD, et al. Relationships among pain, anxiety, and depression in primary care. Depress Anxiety. 2008;25(7):593-600.http://www.ncbi.nlm.nih.gov/pubmed/17932958?tool=bestpractice.com
丙米嗪和氯米帕明都是有效的。[83]Barlow DH, Gorman JM, Shear MK, et al. Cognitive-behavioral therapy, imiprimine, or their combination for panic disorder: a randomized controlled trial. JAMA. 2000 May 17;283(19):2529-36.http://jama.jamanetwork.com/article.aspx?articleid=192707http://www.ncbi.nlm.nih.gov/pubmed/10815116?tool=bestpractice.com[105]Caillard V, Rouillon F, Viel JF, et al. Comparative effects of low and high doses of clomipramine and placebo in panic disorder: a double-blind controlled study. Acta Psychiatr Scand. 1999 Jan;99(1):51-8.http://www.ncbi.nlm.nih.gov/pubmed/10066007?tool=bestpractice.com 但这些药物的不良反应大,没有SSRIs和SNRIs的耐受性好,并且过量致死风险更高,所以较不推荐。[75]Roy-Byrne PP, Cowley DS. Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia, and social anxiety disorder. In: Nathan P, Gorman JM, eds. A guide to treatments that work. 3rd ed. New York, NY: Oxford University Press; 2007:337-66.
伴共病的惊恐障碍
焦虑障碍和抑郁障碍可能存在于惊恐障碍之前、同时或之后。 伴严重焦虑或抑郁的患者,应转诊给精神科医生。
共病抑郁:
患者初始治疗选择为CBT或SSRI,或对一种或多种SSRI或CBT治疗失败时选择TCA。 对于共病抑郁的患者,苯二氮䓬类药物是相对禁忌使用的。[75]Roy-Byrne PP, Cowley DS. Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia, and social anxiety disorder. In: Nathan P, Gorman JM, eds. A guide to treatments that work. 3rd ed. New York, NY: Oxford University Press; 2007:337-66.
难治性共病抑郁的STAR*D研究指南推荐,如果患者使用1种抗抑郁剂最大剂量仅获得部分效果(症状改善25%),建议采用两种药物治疗。[106]Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007 Feb;164(2):201-4.http://www.ncbi.nlm.nih.gov/pubmed/17267779?tool=bestpractice.com 考虑两种不同种类作用机制的药物联合使用,不同种类包括:SSRI(帕罗西汀、舍曲林、氟西汀、氟伏沙明、西酞普兰和艾司西酞普兰),SNRI(文拉法辛),米氮平以及TCA(丙米嗪、氯米帕明)。 要检查药物相互作用,在联合治疗开始前,应咨询精神科医生。
对于惊恐障碍伴严重抑郁和/或共病物质滥用的患者,CBT 治疗有效。[107]Rathgeb-Fuetsch M, Kempter G, Feil A, et al. Short- and long- term efficacy of cognitive behavioral therapy for DSM-IV panic disorder in patients with and without severe psychiatric comorbidity. J Psychiatr Res. 2011 Sep;45(9):1264-8.http://www.ncbi.nlm.nih.gov/pubmed/21536308?tool=bestpractice.com 不论抑郁严重程度,基于暴露的CBT治疗能够有效减轻患者的焦虑和共病抑郁症状。[108]Emmrich A, Beesdo-Baum K, Gloster AT, et al. Depression does not affect the treatment outcome of CBT for panic and agoraphobia: results from a multicenter randomized trial. Psychother Psychosom. 2012;81(3):161-72.http://www.ncbi.nlm.nih.gov/pubmed/22399019?tool=bestpractice.com 使用药物治疗的患者,也建议联合CBT治疗。
共病焦虑(如广场恐怖症、社交焦虑障碍、创伤后应激障碍):
治疗可以从伴或不伴CBT的药物治疗(如SSRI、SNRI、苯二氮䓬类药物和TCA)开始,或从单用CBT开始。 苯二氮䓬类药物和TCA作为二线药物治疗选择。
高效苯二氮䓬类药物可以增强 SSRI 的疗效,尤其当强烈的持续焦虑症状干扰治疗依从性和参与性以及需要快速控制焦虑症状时。[54]American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder, second edition. 2009 [internet publication].http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/panicdisorder.pdf[109]Bystritsky A. Treatment-resistant anxiety disorders. Mol Psychiatry. 2006 Sep;11(9):805-14.http://www.ncbi.nlm.nih.gov/pubmed/16847460?tool=bestpractice.com