非药物疗法和安眠药治疗被认为是失眠症治疗的一线疗法。
非药物疗法
对可能导致持续性睡眠障碍的任何基础疾病(如慢性疼痛、潮热)或精神疾病(如抑郁)的识别和优化治疗是非常重要的。
认知行为疗法 (CBT)、睡眠卫生教育以及松弛技术是失眠症的所有适当的非药物一线治疗方案,特别是不喜欢使用药物或对安眠药无反应的患者。[49]Morin CM, Bootzin RR, Buysse DJ, et al. Psychological and behavioral treatment of insomnia:update of the recent evidence (1998-2004). Sleep. 2006;29:1398-1414.http://www.ncbi.nlm.nih.gov/pubmed/17162986?tool=bestpractice.com[50]Morin CM, Vallières A, Guay B, et al. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial. JAMA. 2009;301:2005-2015.http://jama.ama-assn.org/content/301/19/2005.longhttp://www.ncbi.nlm.nih.gov/pubmed/19454639?tool=bestpractice.com[51]Cheng SK, Dizon J. Computerised cognitive behavioural therapy for insomnia: a systematic review and meta-analysis. Psychother Psychosom. 2012;81:206-216.http://www.ncbi.nlm.nih.gov/pubmed/22585048?tool=bestpractice.com[52]Mitchell MD, Gehrman P, Perlis M, et al. Comparative effectiveness of cognitive behavioral therapy for insomnia: a systematic review. BMC Fam Pract. 2012;13:40.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481424/http://www.ncbi.nlm.nih.gov/pubmed/22631616?tool=bestpractice.com[53]Buysse DJ. Insomnia. JAMA. 2013;309:706-716.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632369/http://www.ncbi.nlm.nih.gov/pubmed/23423416?tool=bestpractice.com[54]Sun J, Kang J, Wang P, et al. Self-relaxation training can improve sleep quality and cognitive functions in the older: a one-year randomised controlled trial. J Clin Nurs. 2013;22:1270-1280.http://www.ncbi.nlm.nih.gov/pubmed/23574290?tool=bestpractice.com[55]Vitiello MV, McCurry SM, Shortreed SM, et al. Cognitive-behavioral treatment for comorbid insomnia and osteoarthritis pain in primary care: the lifestyles randomized controlled trial. J Am Geriatr Soc. 2013;61:947-956.http://www.ncbi.nlm.nih.gov/pubmed/23711168?tool=bestpractice.com[56]Black DS, O'Reilly GA, Olmstead R, et al. Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances: a randomized clinical trial. JAMA Intern Med. 2015;175:494-501.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407465/http://www.ncbi.nlm.nih.gov/pubmed/25686304?tool=bestpractice.com[57]Wu JQ, Appleman ER, Salazar RD, et al. Cognitive behavioral therapy for insomnia comorbid with psychiatric and medical conditions: a meta-analysis. JAMA Intern Med. 2015;175:1461-1472.http://www.ncbi.nlm.nih.gov/pubmed/26147487?tool=bestpractice.com[58]Brasure M, Fuchs E, MacDonald R, et al. Psychological and behavioral interventions for managing insomnia disorder: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2016;165:113-124.http://www.ncbi.nlm.nih.gov/pubmed/27136619?tool=bestpractice.com[59]Brasure M, MacDonald R, Fuchs E, et al; Agency for Healthcare Research and Quality. Management of insomnia disorder. 2015. https://www.ahrq.gov/ (last accessed 7 December 2016).https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0084673/pdf/PubMedHealth_PMH0084673.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26844312?tool=bestpractice.com
已经证明,CBT 可有效地长期治疗失眠症但需要患者承诺和从业医生培训。[60]Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Psychiatry. 1994;151:1172-1180.http://www.ncbi.nlm.nih.gov/pubmed/8037252?tool=bestpractice.com改善老年人睡眠质量:中等质量的证据表明,与不治疗相比,CBT(睡眠卫生、刺激控制、睡眠限制、肌肉松弛和睡眠教育)在改善原发性失眠症老年患者的睡眠结局方面更有效。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。CBT 治疗 12 个月后症状显著改善,且初始结合安眠药治疗可能有益。[50]Morin CM, Vallières A, Guay B, et al. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial. JAMA. 2009;301:2005-2015.http://jama.ama-assn.org/content/301/19/2005.longhttp://www.ncbi.nlm.nih.gov/pubmed/19454639?tool=bestpractice.com
睡眠卫生包含建立有利于睡眠的习惯,如保持有规律的作息时间、避免日间小睡、上床前避免饮酒以及避免咖啡因。[61]Sin CW, Ho JS, Chung JW. Systematic review on the effectiveness of caffeine
abstinence on the quality of sleep. J Clin Nurs. 2009;18:13-21.http://www.ncbi.nlm.nih.gov/pubmed/19120728?tool=bestpractice.com
补充疗法、草药或替代疗法(如针灸或顺势疗法)已考虑用于治疗失眠症,但研究不支持其应用,[62]Taibi DM, Landis CA, Petry H, et al. A systematic review of valerian as
a sleep aid: safe but not effective. Sleep Med Rev. 2007;11:209-230.http://www.ncbi.nlm.nih.gov/pubmed/17517355?tool=bestpractice.com[63]Meolie AL, Rosen C, Kristo D, et al. Oral nonprescription treatment for
insomnia: an evaluation of products with limited evidence. J Clin Sleep Med. 2005;1:173-187.http://www.ncbi.nlm.nih.gov/pubmed/17561634?tool=bestpractice.com[64]Cooper KL, Relton C. Homeopathy for insomnia: a systematic review of research evidence. Sleep Med Rev. 2010;14:329-337.http://www.ncbi.nlm.nih.gov/pubmed/20223686?tool=bestpractice.com[65]Cooper KL, Relton C. Homeopathy for insomnia: summary of additional RCT published since systematic review. Sleep Med Rev. 2010;14:411.http://www.ncbi.nlm.nih.gov/pubmed/20817511?tool=bestpractice.com或需要进一步研究以确定其疗效。[66]Kalavapalli R, Singareddy R. Role of acupuncture in the treatment of insomnia:
a comprehensive review. Complement Ther Clin Pract. 2007;13:184-193.http://www.ncbi.nlm.nih.gov/pubmed/17631261?tool=bestpractice.com
已经证明,非药物治疗可有效治疗与其他疾病(如阿尔茨海默病[67]Deschenes CL, McCurry SM. Current treatments for sleep disturbances in
individuals with dementia. Curr Psychiatry Rep. 2009;11:20-26.http://www.ncbi.nlm.nih.gov/pubmed/19187704?tool=bestpractice.com[68]McCurry SM, Gibbons LE, Logsdon RG, et al. Nighttime insomnia treatment and education for Alzheimer's disease: a randomized, controlled trial. J Am Geriatr Soc. 2005;53:793-802.http://www.ncbi.nlm.nih.gov/pubmed/15877554?tool=bestpractice.com和创伤后应激障碍)并存的失眠症。[69]Lamarche LJ, De Koninck J. Sleep disturbance in adults with posttraumatic
stress disorder: a review. J Clin Psychiatry. 2007;68:1257-1270.http://www.ncbi.nlm.nih.gov/pubmed/17854251?tool=bestpractice.com
当在临床医生的指导下进行时,非药物干预是有益的。自助治疗具有小至中度疗效。[70]van Straten A, Cuijpers P. Self-help therapy for insomnia: a meta-analysis.
Sleep Med Rev. 2009;13:61-71.http://www.ncbi.nlm.nih.gov/pubmed/18952469?tool=bestpractice.com[71]Yang PY, Ho KH, Chen HC, et al. Exercise training improves sleep quality in middle-aged and older adults with sleep problems: a systematic review. J Physiother. 2012;58:157-163.http://www.ncbi.nlm.nih.gov/pubmed/22884182?tool=bestpractice.com
安眠药
安眠药可单独使用或联合非药物疗法一起使用。较新的非苯二氮䓬类药物受体激动剂例如右佐匹克隆、[72]Ancoli-Israel S, Krystal AD, McCall WV, et al. A 12-week, randomized, double-blind, placebo-controlled study evaluating the effect of eszopiclone 2 mg on sleep/wake function in older adults with primary and comorbid insomnia. Sleep. 2010;33:225-234.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817909/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/20175406?tool=bestpractice.com扎来普隆、唑吡坦等和褪黑激素 MT1/MT2 受体激动剂雷美替胺对于长期使用似乎更安全且优于传统的苯二氮䓬类药物。多塞平是一种选择性 H1 受体拮抗剂,已经证明其能有效治疗短暂性失眠症,改善入睡后觉醒 (WASO)、总睡眠时间以及入睡潜伏期。[73]Roth T, Heith Durrence H, Jochelson P, et al. Efficacy and safety of doxepin 6 mg in a model of transient insomnia. Sleep Med. 2010;11:843-847.http://www.ncbi.nlm.nih.gov/pubmed/20817598?tool=bestpractice.com[74]Krystal AD, Lankford A, Durrence HH, et al. Efficacy and safety of doxepin 3 and 6 mg in a 35-day sleep laboratory trial in adults with chronic primary insomnia. Sleep. 2011;34:1433-1442.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174845/http://www.ncbi.nlm.nih.gov/pubmed/21966075?tool=bestpractice.com低剂量多塞平在慢性失眠症老年患者中也具有良好的疗效和安全性特征。[75]Krystal AD, Durrence HH, Scharf M, et al. Efficacy and safety of doxepin 1 mg and 3 mg in a 12-week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia. Sleep. 2010;33:1553-1561.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954705/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/21102997?tool=bestpractice.com[76]Krystal AD, Durrence HH, Scharf M, et al. Efficacy and safety of doxepin 1 mg and 3 mg in a 12-week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia. Sleep. 2010;33:1553-1561.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954705/http://www.ncbi.nlm.nih.gov/pubmed/21102997?tool=bestpractice.com[77]Lankford A, Rogowski R, Essink B, et al. Efficacy and safety of doxepin 6 mg in a four-week outpatient trial of elderly adults with chronic primary insomnia. Sleep Medicine. 2012;13:133-138.http://www.ncbi.nlm.nih.gov/pubmed/22197474?tool=bestpractice.comSuvorexant(一种双食欲素受体拮抗剂)通过结合性抑制食欲素 A 和 B(促进觉醒的神经肽类)阻断两种食欲素受体(OX1R 和 OX2R)从而改善睡眠。[78]Herring WJ, Snyder E, Budd K, et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012;79:2265-2274.http://www.ncbi.nlm.nih.gov/pubmed/23197752?tool=bestpractice.com与安慰剂相比,已经证明此药能改善整体和睡眠结局,[59]Brasure M, MacDonald R, Fuchs E, et al; Agency for Healthcare Research and Quality. Management of insomnia disorder. 2015. https://www.ahrq.gov/ (last accessed 7 December 2016).https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0084673/pdf/PubMedHealth_PMH0084673.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26844312?tool=bestpractice.com[79]Wilt TJ, MacDonald R, Brasure M, et al. Pharmacologic treatment of insomnia disorder: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2016;165:103-112.http://www.ncbi.nlm.nih.gov/pubmed/27136278?tool=bestpractice.com且适用于治疗 18 岁及以上成人的入睡障碍性失眠及维持睡眠障碍性失眠。
非苯二氮卓类安眠药优于苯二氮卓类药物,原因是不良作用风险更低(特别是次日残余镇静作用)[80]Lieberman JA. Update on the safety considerations in the management of
insomnia with hypnotics: incorporating modified-release formulations into primary
care. Prim Care Companion J Clin Psychiatry. 2007;9:25-31.http://www.ncbi.nlm.nih.gov/pubmed/17599165?tool=bestpractice.com且产生依赖性的可能性更低。苯二氮卓类药物极少推荐用于治疗失眠症。一些安眠药依赖于新的作用机制。同其他安眠药一样,雷美替胺对 GABA 受体没有作用,仅作用于 MT1/MT2 受体。
对于入睡困难的患者,已知能够缩短睡眠潜伏期的安眠药可能是一线治疗药物。这些药物包括唑吡坦、艾司佐匹克隆、扎来普隆和雷美替胺。
对于那些维持睡眠困难的患者,适合已知能够减少入睡后觉醒的安眠药,包括半衰期较长的安眠药以及延长药物作用时间的制剂。这些药物包括唑吡坦(缓释剂)和艾司佐匹克隆。新型安眠药适用于治疗失眠症,且其使用时间没有限制;一些患者可能需要长期使用。
已经证明,安眠药联合抗抑郁剂或抗焦虑剂分别在治疗失眠症并存抑郁和焦虑时有疗效。[81]Pollack M, Kinrys G, Krystal A, et al. Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Arch Gen Psychiatry.
2008;65:551-562.http://www.ncbi.nlm.nih.gov/pubmed/18458207?tool=bestpractice.com[82]Ji JL, Liu WJ, Zhang N, et al. Effects of paroxetine with or without zolpidem on depression with insomnia: a multi-center randomized comparative study. [Article in Chinese.] Zhonghua Yi Xue Za Zhi. 2007;87:1585-1589.http://www.ncbi.nlm.nih.gov/pubmed/17803844?tool=bestpractice.com[83]Fava M, Asnis GM, Shrivastava R, et al. Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder. J Clin Psychopharmacol. 2009;29:222-230.http://www.ncbi.nlm.nih.gov/pubmed/19440075?tool=bestpractice.com[84]Stein DJ, Lopez AG, Stein DJ, et al. Effects of escitalopram on sleep problems in patients with major depression or generalized anxiety disorder. Adv Ther. 2011;28:1021-1037.http://www.ncbi.nlm.nih.gov/pubmed/22057726?tool=bestpractice.com[85]Ensrud KEJ, Sternfeld BL. Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes: a randomized controlled trial. Menopause. 2012;19:848-855.http://www.ncbi.nlm.nih.gov/pubmed/22433978?tool=bestpractice.com[86]Fava M, Asnis GM, Shrivastava RK, et al. Improved insomnia symptoms and sleep-related next-day functioning in patients with comorbid major depressive disorder and insomnia following concomitant zolpidem extended-release 12.5 mg and escitalopram treatment: a randomized controlled trial. J Clin Psychiatry. 2011;72:914-928.http://www.ncbi.nlm.nih.gov/pubmed/21208597?tool=bestpractice.com间歇性给药方案已经考虑用于失眠症的长期治疗。[87]Perlis M, Gehrman P, Riemann D. Intermittent and long-term use of sedative
hypnotics. Curr Pharm Des. 2008;14:3456-3465.http://www.ncbi.nlm.nih.gov/pubmed/19075721?tool=bestpractice.com
重要的是,怀孕期间不得使用这些药物且有酒精或药物滥用史的患者应当慎用。美国食品和药物管理局 (FDA) 建议降低唑吡坦的睡前剂量,因为数据表明,一些患者使用后,次日早上的血液药物水平足以影响需要警觉性的活动,包括驾驶。数据显示患者服用缓释制剂时,风险最高,且女性似乎对该风险更为敏感,因为唑吡坦在女性患者体内的排泄速度比男性慢。FDA 也提醒公众,右佐匹克隆会削弱次日的驾驶能力和其他需要警觉性的活动能力。因此,已减少推荐起始剂量,因为较高剂量更可能导致次日损伤。较大剂量的 Suvorexant 可能导致第二天嗜睡并影响日常活动。[78]Herring WJ, Snyder E, Budd K, et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012;79:2265-2274.http://www.ncbi.nlm.nih.gov/pubmed/23197752?tool=bestpractice.com治疗失眠症的所有药物都有次日早晨嗜睡的风险,治疗患者症状时应使用最低剂量。
镇静作用抗组胺药和抗抑郁剂有时可用于治疗失眠症;但缺乏其疗效相关证据。