实施治疗计划之前,对患者进行关于其疾病的宣教非常重要,[45]Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388-2395.http://jama.ama-assn.org/cgi/content/full/292/19/2388http://www.ncbi.nlm.nih.gov/pubmed/15547167?tool=bestpractice.com强调纤维肌痛是可控制但不可治愈的,大多数患者通过接受积极治疗可以恰当地行使功能,治疗可能包括药物治疗和非药物治疗。通常在非药物治疗之前就启动药物治疗是有帮助的,因为患者用药后症状有一定的改善,能使其对运动和认知行为治疗有更好的依从性。
治疗概述
疗效证据最多的药物种类包括:三环类抗抑郁药(tricyclic antidepressant, TCA;例如阿米替林、环苯扎林), [
]How effective and safe is amitriptyline for treatment of adults with fibromyalgia?http://cochraneclinicalanswers.com/doi/10.1002/cca.1525/full显示答案 5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI;例如度洛西汀、米那普仑), [
]What are the benefits and harms of serotonin and noradrenaline reuptake inhibitors (SNRIs) in people with fibromyalgia syndrome?http://cochraneclinicalanswers.com/doi/10.1002/cca.138/full显示答案 以及加巴喷丁类药物(例如普瑞巴林、加巴喷丁)。 [
]In people with fibromyalgia, how do anticonvulsants affect outcomes?http://cochraneclinicalanswers.com/doi/10.1002/cca.404/full显示答案 患者经常获益于两或三类药物联用,而部分患者仅需要使用其中一类药物即可。[46]Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311:1547-1555.http://www.ncbi.nlm.nih.gov/pubmed/24737367?tool=bestpractice.com
可能首先应该让所有患者尝试一种或两种 TCA,因为这些药物价格便宜,如果有效,经常可在改善疼痛的同时改善睡眠和内脏活动。如果患者存在抑郁或者疲劳,则 SNRI 是首选用药。如果患者存在显著的睡眠障碍,则加巴喷丁可能是更好的首选药物(尤其是在睡前即刻给药或大部分药量在睡前使用)。
一旦患者注意到自己的症状通过药物治疗有所改善,临床医生就应该倡导使用非药物疗法,例如教育、运动[47]Bidonde J, Busch AJ, Schachter CL, et al. Aerobic exercise training for adults with fibromyalgia. Cochrane Database Syst Rev. 2017;(6):CD012700.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012700/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28636204?tool=bestpractice.com及认知行为疗法。多种疗法将运动与放松相结合,例如瑜伽和太极,[48]Wang C, Schmid CH, Rones R, et al. A randomized trial of tai chi for fibromyalgia. N Engl J Med. 2010;363:743-754.http://www.nejm.org/doi/full/10.1056/NEJMoa0912611http://www.ncbi.nlm.nih.gov/pubmed/20818876?tool=bestpractice.com已经表明这些疗法有效。
应用这种治疗后,大多数纤维肌痛患者症状有明显改善,并且能够在存在疾病的情况下正常生活。一些患者可能对上述治疗无反应,并且需要跨学科治疗,尤其是症状长期持续并且影响生活功能(例如残疾、失代偿)的患者,依赖大剂量阿片类药物的患者,有严重精神科共病的患者,以及接受多次外科治疗失败的患者。
有多篇综述和 meta 分析提供了关于纤维肌痛长期治疗的细节。[49]Schmidt-Wilcke T, Clauw DJ. Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol. 2011;7:518-527.http://www.ncbi.nlm.nih.gov/pubmed/21769128?tool=bestpractice.com尽管许多临床医生认为纤维肌痛的治疗不如其他慢性疼痛性疾病的治疗有效,然而数据表明,目前治疗纤维肌痛药物的总体效果与治疗其他慢性疼痛药物的大致相同。[50]Clauw DJ. Pain management: Fibromyalgia drugs are 'as good as it gets' in chronic pain. Nat Rev Rheumatol. 2010;6:439-440.http://www.ncbi.nlm.nih.gov/pubmed/20676122?tool=bestpractice.com
抗抑郁药
5-羟色胺和去甲肾上腺素再摄取抑制剂 (SNRI) 度洛西汀和米那普仑被认为是治疗纤维肌痛的有效药物。 [
]What are the benefits and harms of serotonin and noradrenaline reuptake inhibitors (SNRIs) in people with fibromyalgia syndrome?http://cochraneclinicalanswers.com/doi/10.1002/cca.138/full显示答案 用药前告知患者药物有恶心的风险,安慰患者大多数病例的恶心症状都是一过性的,以及从低剂量开始逐渐缓慢递增药物剂量等这些措施都可以增加患者对这些药物的耐受性。这些药物的有效性和耐受性似乎可持续长达 1 年。[51]Mease PJ, Russell IJ, Kajdasz DK, et al. Long-term safety, tolerability, and efficacy of duloxetine in the treatment of fibromyalgia. Semin Arthritis Rheum. 2010;39:454-464.http://www.ncbi.nlm.nih.gov/pubmed/19152958?tool=bestpractice.com40% 的女性使用度洛西汀 12 周后平均疼痛减轻>50%。[51]Mease PJ, Russell IJ, Kajdasz DK, et al. Long-term safety, tolerability, and efficacy of duloxetine in the treatment of fibromyalgia. Semin Arthritis Rheum. 2010;39:454-464.http://www.ncbi.nlm.nih.gov/pubmed/19152958?tool=bestpractice.com度洛西汀最常见的副作用是恶心和头疼。[52]Brunton S, Wang F, Edwards SB, et al. Profile of adverse events with duloxetine treatment: a pooled analysis of placebo-controlled studies. Drug Saf. 2010;33:393-407.http://www.ncbi.nlm.nih.gov/pubmed/20397739?tool=bestpractice.com[53]Choy EH, Mease PJ, Kajdasz DK, et al. Safety and tolerability of duloxetine in the treatment of patients with fibromyalgia: pooled analysis of data from five clinical trials. Clin Rheumatol. 2009;28:1035-1044.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721139/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/19533210?tool=bestpractice.com [
]What are the benefits and harms of serotonin and noradrenaline reuptake inhibitors (SNRIs) in people with fibromyalgia syndrome?http://cochraneclinicalanswers.com/doi/10.1002/cca.138/full显示答案 与安慰剂相比,米那普仑可降低每周疼痛评分。[54]Gendreau RM, Thorn MD, Gendreau JF, et al. Efficacy of milnacipran in patients with fibromyalgia. J Rheumatol. 2005;32:1975-1985.http://www.ncbi.nlm.nih.gov/pubmed/16206355?tool=bestpractice.com[55]Mease PJ, Clauw DJ, Gendreau RM, et al. The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial. J Rheumatol. 2009;36:398-409.http://www.ncbi.nlm.nih.gov/pubmed/19132781?tool=bestpractice.com[56]Clauw DJ, Mease P, Palmer RH, et al. Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial. Clin Ther. 2008;30:1988-2004.http://www.ncbi.nlm.nih.gov/pubmed/19108787?tool=bestpractice.com[57]Kyle JA, Dugan BD, Testerman KK. Milnacipran for treatment of fibromyalgia. Ann Pharmacother. 2010;44:1422-1429.http://www.ncbi.nlm.nih.gov/pubmed/20716692?tool=bestpractice.com[58]Arnold LM, Gendreau RM, Palmer RH, et al. Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62:2745-2756.http://www.ncbi.nlm.nih.gov/pubmed/20496365?tool=bestpractice.com [
]Does milnacipran improve pain in adults with fibromyalgia?http://cochraneclinicalanswers.com/doi/10.1002/cca.1150/full显示答案 胃肠道不适、多汗、头痛是最常报告的副作用。[54]Gendreau RM, Thorn MD, Gendreau JF, et al. Efficacy of milnacipran in patients with fibromyalgia. J Rheumatol. 2005;32:1975-1985.http://www.ncbi.nlm.nih.gov/pubmed/16206355?tool=bestpractice.com[58]Arnold LM, Gendreau RM, Palmer RH, et al. Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62:2745-2756.http://www.ncbi.nlm.nih.gov/pubmed/20496365?tool=bestpractice.com[59]Branco JC, Zachrisson O, Perrot S, et al. A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia. J Rheumatol. 2010;37:851-859.http://www.ncbi.nlm.nih.gov/pubmed/20156949?tool=bestpractice.com [
]What are the benefits and harms of serotonin and noradrenaline reuptake inhibitors (SNRIs) in people with fibromyalgia syndrome?http://cochraneclinicalanswers.com/doi/10.1002/cca.138/full显示答案
在 SNRI 受到青睐之前,三环类抗抑郁药(例如阿米替林和环苯扎林)是纤维肌痛治疗药物中被研究最多的,并且最常用于该适应证,[60]Arnold LM, Keck PE Jr, Welge JA. Antidepressant treatment of fibromyalgia: a meta-analysis and review. Psychosomatics. 2000;41:104-113.http://www.ncbi.nlm.nih.gov/pubmed/10749947?tool=bestpractice.com这类药物也可能是通过阻止 5-羟色胺和去甲肾上腺素再摄取起效的。可能首先应该让所有患者尝试一种或两种 TCA,因为这些药物价格便宜,如果有效,经常可在改善疼痛的同时改善睡眠和内脏活动。meta 分析证实了一些个体试验的结果,提示预期有 30% 的患者出现具有意义的临床反应,[60]Arnold LM, Keck PE Jr, Welge JA. Antidepressant treatment of fibromyalgia: a meta-analysis and review. Psychosomatics. 2000;41:104-113.http://www.ncbi.nlm.nih.gov/pubmed/10749947?tool=bestpractice.com[61]Tofferi JK, Jackson JL, O'Malley PG. Treatment of fibromyalgia with cyclobenzaprine: a meta-analysis. Arthritis Rheum. 2004;51:9-13.http://onlinelibrary.wiley.com/doi/10.1002/art.20076/fullhttp://www.ncbi.nlm.nih.gov/pubmed/14872449?tool=bestpractice.com[62]O'Malley PG, Balden E, Tomkins G, et al. Treatment of fibromyalgia with antidepressants. J Gen Intern Med. 2000;15:659-666.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495596/http://www.ncbi.nlm.nih.gov/pubmed/11029681?tool=bestpractice.com改善纤维肌痛患者的睡眠差和疼痛:有高质量的证据表明,在运动和/或 CBT 的基础上加用三环类抗抑郁药可能对有睡眠障碍和持久疼痛的纤维肌痛患者有益。[61]Tofferi JK, Jackson JL, O'Malley PG. Treatment of fibromyalgia with cyclobenzaprine: a meta-analysis. Arthritis Rheum. 2004;51:9-13.http://onlinelibrary.wiley.com/doi/10.1002/art.20076/fullhttp://www.ncbi.nlm.nih.gov/pubmed/14872449?tool=bestpractice.com[60]Arnold LM, Keck PE Jr, Welge JA. Antidepressant treatment of fibromyalgia: a meta-analysis and review. Psychosomatics. 2000;41:104-113.http://www.ncbi.nlm.nih.gov/pubmed/10749947?tool=bestpractice.com[62]O'Malley PG, Balden E, Tomkins G, et al. Treatment of fibromyalgia with antidepressants. J Gen Intern Med. 2000;15:659-666.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495596/http://www.ncbi.nlm.nih.gov/pubmed/11029681?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。但仍无很好的证据显示获益可以持续超过 8 周。[63]Nishishinya B, Urrútia G, Walitt B, et al. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford). 2008;47:1741-1746.http://rheumatology.oxfordjournals.org/cgi/content/full/47/12/1741http://www.ncbi.nlm.nih.gov/pubmed/18697829?tool=bestpractice.com如果尝试治疗 6 周后仍没有获益,则停药。如果药物最初有效但似乎疗效减弱,则可以暂停一段时间后再次尝试用药。三环类药物的抗胆碱能副作用经常影响其耐受性,对于老年患者更是如此。然而,此类药物的一个好处是可改善睡眠。
SNRI 和三环类抗抑郁药可以一起使用(例如 SNRI 早晨给药,TRC 晚上给药);然而,联合使用这两类药物的患者存在发生 5-羟色胺综合征的风险,但认为这种风险在临床上罕见。
应该注意的是,抗抑郁药对纤维肌痛和其他慢性疼痛疾病的疗效似乎是独立于其抗抑郁作用的,[64]Häuser W, Bernardy K, Uçeyler N, et al. Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis. JAMA. 2009;301:198-209.http://jama.jamanetwork.com/article.aspx?articleid=183189#qundefinedhttp://www.ncbi.nlm.nih.gov/pubmed/19141768?tool=bestpractice.com并不是所有的抗抑郁药都对疼痛或纤维肌痛有效。此外,去甲肾上腺素似乎是与慢性疼痛相关的最重要两种神经递质之一,已经证明去甲肾上腺素再摄取抑制剂瑞波西汀对纤维肌痛有效,然而,未表明选择性 5-羟色胺再摄取抑制剂对治疗临床前和临床慢性疼痛疾病有效。[65]Arnold LM, Chatamra K, Hirsch I, et al. Safety and efficacy of esreboxetine in patients with fibromyalgia: An 8-week, multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2010;32:1618-1632.http://www.ncbi.nlm.nih.gov/pubmed/20974319?tool=bestpractice.com
加巴喷丁类
加巴喷丁类药物是另一类用于治疗纤维肌痛的药物。普瑞巴林被批准用于该适应证; [
]In people with fibromyalgia, how do anticonvulsants affect outcomes?http://cochraneclinicalanswers.com/doi/10.1002/cca.404/full显示答案 不过,加巴喷丁在治疗纤维肌痛方面表现出相似的效果。[66]Arnold LM, Goldenberg DL, Stanford SB, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum. 2007;56:1336-1344.http://onlinelibrary.wiley.com/doi/10.1002/art.22457/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17393438?tool=bestpractice.com这些药物有镇痛以及抗焦虑和抗惊厥的作用。[67]Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52:1264-1273.http://onlinelibrary.wiley.com/doi/10.1002/art.20983/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15818684?tool=bestpractice.com这两种药物的副作用无显著差异。Meta 分析研究支持使用这两种药物中的任何一种,并指出这些药物可减轻疼痛、改善睡眠,并改善健康相关生活质量 (health-related quality of life, HRQOL)。[68]Moore RA, Straube S, Wiffen PJ, et al. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009;(3):CD007076.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007076.pub2/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/19588419?tool=bestpractice.com[69]Häuser W, Bernardy K, Uçeyler N, et al. Treatment of fibromyalgia syndrome with gabapentin and pregabalin: a meta-analysis of randomized controlled trials. Pain. 2009;145:69-81.http://www.ncbi.nlm.nih.gov/pubmed/19539427?tool=bestpractice.com [
]In people with fibromyalgia, how do anticonvulsants affect outcomes?http://cochraneclinicalanswers.com/doi/10.1002/cca.404/full显示答案 [
]What are the effects of recommended doses of pregabalin given for pain relief to people with fibromyalgia?http://cochraneclinicalanswers.com/doi/10.1002/cca.1524/full显示答案 如果在睡前给予高比例的剂量(或是全部剂量),往往有更好的耐受性。
镇痛
虽然非甾体抗炎药 (NSAID) 和阿片类药物对急性疼痛非常有效,也是治疗长期伤害性疼痛状态(即疼痛主要是由外周组织损伤所致)的一线药物之一,但没有证据表明单用此类药物对纤维肌痛有效。然而,如果纤维肌痛合并一些有持续外周伤害性输入的疾病(例如骨关节炎),则使用 NSAID(例如萘普生)或阿片类药物(例如曲马多)可能有效。尽管普遍并不推荐应用这些药物治疗纤维肌痛,并且担忧存在增加阿片类药物诱导痛觉过敏的风险(主要是个案研究),但是目前仍然普遍使用这些药物。
非药物疗法
非药物治疗应作为纤维肌痛及其他慢性疼痛疾患整体治疗策略中的关键部分,但往往在临床实践中并没有充分使用。 [
]In people with fibromyalgia, how do psychological therapies affect outcomes?http://cochraneclinicalanswers.com/doi/10.1002/cca.914/full显示答案 这些治疗中具有最一致有效性的方法包括患者教育、认知行为疗法和运动。[70]Busch AJ, Webber SC, Richards RS, et al. Resistance exercise training for fibromyalgia. Cochrane Database Syst Rev. 2013;(12):CD010884.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010884/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24362925?tool=bestpractice.com[71]Bernardy K, Klose P, Busch AJ, et al. Cognitive behavioural therapies for fibromyalgia. Cochrane Database Syst Rev. 2013;(9):CD009796.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009796.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24018611?tool=bestpractice.com [
]In people with fibromyalgia, what are the effects of cognitive behavioral therapies?http://cochraneclinicalanswers.com/doi/10.1002/cca.423/full显示答案 [
]In people with fibromyalgia, is there randomized controlled trial evidence to support the use of resistance exercise training?http://cochraneclinicalanswers.com/doi/10.1002/cca.646/full显示答案 几乎所有类型的运动都有益处,有一些证据表明,对于很多纤维肌痛患者,水上运动是开始一项运动计划的很好方式。[72]Bidonde J, Busch AJ, Webber SC, et al. Aquatic exercise training for fibromyalgia. Cochrane Database Syst Rev. 2014;(10):CD011336.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011336/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25350761?tool=bestpractice.com[73]Barker AL, Talevski J, Morello RT, et al. Effectiveness of aquatic exercise for musculoskeletal conditions: a meta-analysis. Arch Phys Med Rehabil. 2014;95:1776-1786.http://www.ncbi.nlm.nih.gov/pubmed/24769068?tool=bestpractice.com治疗抑郁和焦虑是大多数临床医生的共识,而认知行为疗法 (CBT) 和生物反馈作为针对性治疗技术往往比许多药物治疗更有效。并不是所有精神病学家和心理学家都能提供这项技术,许多患者无法找到经过培训的医生。正因为如此,许多团队试图表明以互联网为基础的方案(整合教育、CBT、运动)对纤维肌痛与其他慢性疼痛状态可能有效。[74]Williams DA, Kuper D, Segar M, et al. Internet-enhanced management of fibromyalgia: a randomized controlled trial. Pain. 2010;151:694-702.http://www.ncbi.nlm.nih.gov/pubmed/20855168?tool=bestpractice.com这些方案的内容也在审查和完善之中,同时一些研究表明,即使不是正规的锻炼,较积极的锻炼也对纤维肌痛有益;并且这种 CBT 鼓励患者识别和倾诉早期生活压力事件,通过成功应对这些事件可治愈部分患者,而典型的 CBT 仅提供缓和作用。与其他方法相比,这些干预措施的性价比很高。[75]Luciano JV, Sabes-Figuera R, Cardeñosa E, et al. Cost-utility of a psychoeducational intervention in fibromyalgia patients compared with usual care: an economic evaluation alongside a 12-month randomized controlled trial. Clin J Pain. 2013;29:702-711.http://www.ncbi.nlm.nih.gov/pubmed/23328339?tool=bestpractice.com
转诊
在患者确诊之初就转诊至心理医生处是恰当的做法。