治疗的主要目标是减轻症状的严重程度以及改善生活质量。尽管常使用药物治疗 IBS,对于所使用的大部分药物,缺乏高质量的疗效证据。多个因素导致了这一情况,包括缺少设计良好的大型试验以及安慰剂组的有力表现。[26]Weinberg DS, Smalley W, Heidelbaugh JJ, et al; American Gastroenterological Association. American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome. Gastroenterology. 2014 Nov;147(5):1146-8.http://www.gastrojournal.org/article/S0016-5085(14)01089-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25224526?tool=bestpractice.com
生活方式与饮食调整
对所有的患者而言,建立一个有效的治疗性的医患关系,并向他们提供教育与安慰。初始治疗应该尽量保守,包括讨论改变生活方式从而可能减轻应激反应。可能的刺激性食物,如咖啡因、乳糖或果糖可能需要从食谱中剔除。通过日记来进行症状监测有助于鉴别出参与发病的物质或因素。肠道益生菌治疗可以考虑。[27]Zhang Y, Li L, Guo C, et al. Effects of probiotic type, dose and treatment duration on irritable bowel syndrome diagnosed by Rome III criteria: a meta-analysis. BMC Gastroenterol. 2016 Jun 13;16(1):62.https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-016-0470-zhttp://www.ncbi.nlm.nih.gov/pubmed/27296254?tool=bestpractice.com 有多种菌株可供选择,不同的益生菌对肠道功能的作用可能不同。一种菌株——婴儿双歧杆菌显示出改善 IBS 症状的效果,且目前较其他益生菌是优先选择。[28]Brenner DM, Moeller MJ, Chey WD, et al. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol. 2009 Apr;104(4):1033-49.http://www.ncbi.nlm.nih.gov/pubmed/19277023?tool=bestpractice.com症状改善:有高质量证据表明与安慰剂相比,婴儿双歧杆菌可更显著地改善腹痛/腹部不适、腹胀/胀气和/或排便困难。[28]Brenner DM, Moeller MJ, Chey WD, et al. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol. 2009 Apr;104(4):1033-49.http://www.ncbi.nlm.nih.gov/pubmed/19277023?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 它已经被证实通过改变肠道菌群,从而使得血单核细胞的抗炎与促炎细胞因子比例正常化,提示这一微生物在 IBS 患者的治疗中扮演了免疫调节的角色。[29]O'Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.http://www.ncbi.nlm.nih.gov/pubmed/15765388?tool=bestpractice.com 可发酵寡糖、双糖、单糖和多元醇(以下简称FODMAPs)属于难吸收的短链碳水化合物,在IBS患者中有引起症状的倾向。低FODMAPs的饮食已经显示出改善多个症状的疗效,包括腹泻、肠胀气、腹胀和腹痛。[30]Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014 Jan;146(1):67-75.http://www.gastrojournal.org/article/S0016-5085(13)01407-8/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/24076059?tool=bestpractice.com[31]Ahmad OF, Akbar A. Dietary treatment of irritable bowel syndrome. Br Med Bull. 2015 Mar;113(1):83-90.http://www.ncbi.nlm.nih.gov/pubmed/25601299?tool=bestpractice.com[32]Marsh A, Eslick EM, Eslick GD. Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis. Eur J Nutr. 2016 Apr;55(3):897-906.https://link.springer.com/article/10.1007%2Fs00394-015-0922-1http://www.ncbi.nlm.nih.gov/pubmed/25982757?tool=bestpractice.com[33]Mansueto P, Seidita A, D'Alcamo A, et al. Role of FODMAPs in patients with irritable bowel syndrome. Nutr Clin Pract. 2015 Oct;30(5):665-82.http://journals.sagepub.com/doi/pdf/10.1177/0884533615569886http://www.ncbi.nlm.nih.gov/pubmed/25694210?tool=bestpractice.com[34]Varjú P, Farkas N, Hegyi P I et al. Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: a meta-analysis of clinical studies. PLoS One. 2017 Aug 14;12(8):e0182942.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555627/http://www.ncbi.nlm.nih.gov/pubmed/28806407?tool=bestpractice.com[35]Altobelli E, Del Negro V, Angeletti PM, et al. Low-FODMAP diet improves irritable bowel syndrome symptoms: a meta-analysis. Nutrients. 2017 Aug 26;9(9):E940.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622700/http://www.ncbi.nlm.nih.gov/pubmed/28846594?tool=bestpractice.com这种饮食方式很受欢迎,而且可以通过多种线上资源获得。尚不清楚其是否优于稍传统的饮食。它可使微生物群发生有利的变化,明显减少组胺释放,而组胺在一些患者中是诱因。[36]McIntosh K, Reed DE, Schneider T, et al. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut. 2017 Jul;66(7):1241-51.http://www.ncbi.nlm.nih.gov/pubmed/26976734?tool=bestpractice.com[37]Böhn L, Störsrud S, Liljebo T, et al. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial. Gastroenterology. 2015 Nov;149(6):1399-407.http://www.gastrojournal.org/article/S0016-5085(15)01086-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/26255043?tool=bestpractice.com 对于 FODMAP 食谱的医从性可能是个问题。
腹泻和便秘
如果患者有便秘、或便秘和腹泻交替,则常推荐应用膳食纤维。证据显示,服用卵叶车前(ispaghula,一种膨松剂,有多种专利制剂),睡前一杯液体送服可有助于缓解便秘症状。一项 Meta 分析显示,可溶性膳食纤维比不可溶性膳食纤维更有效。[38]Nagarajan N, Morden A, Bischof D, et al. The role of fiber supplementation in the treatment of irritable bowel syndrome: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2015 Sep;27(9):1002-10.http://www.ncbi.nlm.nih.gov/pubmed/26148247?tool=bestpractice.com 如果添加膳食纤维仍不足以缓解,可加用乳果糖或聚乙二醇。乳果糖在部分患者中可引起腹胀。以便秘为主的 IBS 患者如果无法耐受泻药的治疗,或者粪便软化剂无效,则需使用鲁比前列酮(lubiprostone)。[39]Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome - results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009 Feb 1;29(3):329-41http://www.ncbi.nlm.nih.gov/pubmed/19006537?tool=bestpractice.com[40]Li F, Fu T, Tong WD, et al. Lubiprostone is effective in the treatment of chronic idiopathic constipation and irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc. 2016 Apr;91(4):456-68.http://www.ncbi.nlm.nih.gov/pubmed/27046523?tool=bestpractice.com治疗应答:有中等质量证据表明鲁比前列酮(lubiprostone)对便秘为主的IBS患者而言,比安慰剂显著提升总体治疗应答百分比。[39]Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome - results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009 Feb 1;29(3):329-41http://www.ncbi.nlm.nih.gov/pubmed/19006537?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。 当泻药效果欠佳时,另一备选为利那洛肽(linaclotide),它安全性尚可且对便秘的IBS患者可能有效。[26]Weinberg DS, Smalley W, Heidelbaugh JJ, et al; American Gastroenterological Association. American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome. Gastroenterology. 2014 Nov;147(5):1146-8.http://www.gastrojournal.org/article/S0016-5085(14)01089-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25224526?tool=bestpractice.com[41]Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology. 2010 Dec;139(6):1877-86.http://www.ncbi.nlm.nih.gov/pubmed/20801122?tool=bestpractice.com[42]Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012 Nov;107(11):1702-12.http://www.nature.com/ajg/journal/v107/n11/full/ajg2012254a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/22986437?tool=bestpractice.com美国胃肠病学会 (American Gastroenterology Association, AGA) 指出,对于许多类型的 IBS,利那洛肽 (linaclotide) 是唯一的治疗药物,AGA 可能将该建议作为强烈推荐建议。[26]Weinberg DS, Smalley W, Heidelbaugh JJ, et al; American Gastroenterological Association. American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome. Gastroenterology. 2014 Nov;147(5):1146-8.http://www.gastrojournal.org/article/S0016-5085(14)01089-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25224526?tool=bestpractice.com 美国食品药品监督管理局 (FDA) 也已批准将普卡那肽用于治疗伴有便秘的 IBS。一项系统评价发现,利那洛肽和普卡那肽在治疗伴有便秘的 IBS 方面的疗效和耐受性相似。[43]Shah ED, Kim HM, Schoenfeld P. Efficacy and tolerability of guanylate cyclase-C agonists for irritable bowel syndrome with constipation and chronic idiopathic constipation: a systematic review and meta-analysis. Am J Gastroenterol. 2018 Mar;113(3):329-38.http://www.ncbi.nlm.nih.gov/pubmed/29380823?tool=bestpractice.com
对于腹泻的患者而言,洛哌丁胺可在排稀便后服用。如果患者曾行胆囊切除术,那么这一亚组的患者用考来烯胺 (colestyramine) 的效果可能更好。如果患者仍有症状,应用阿洛司琼(alosetron,一种 5-HT3 受体拮抗剂)可能会有益处,但由于它能增加缺血性结肠炎的风险而可能被限制使用。[44]Ford AC, Brandt LJ, Young C, et al. Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43.http://www.ncbi.nlm.nih.gov/pubmed/19471254?tool=bestpractice.com 已证实,5-HT3 受体拮抗剂可显著改善 IBS 患者的症状。[45]Andresen V, Montori VM, Keller J, et al. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2008 May;6(5):545-55.http://www.ncbi.nlm.nih.gov/pubmed/18242143?tool=bestpractice.com症状改善:中等质量证据表明,5-HT3 拮抗剂阿洛司琼和西兰司琼在整体改善 IBS 症状方面比美贝维林或安慰剂更为有效。[45]Andresen V, Montori VM, Keller J, et al. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2008 May;6(5):545-55.http://www.ncbi.nlm.nih.gov/pubmed/18242143?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。 艾沙度林 (eluxadoline) 是 μ-和 κ-阿片受体的激动剂和 δ-阿片受体的拮抗剂,可缓解伴有腹泻 IBS 患者的腹痛和腹泻,无便秘不良反应。[46]Dove LS, Lembo A, Randall CW, et al. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.http://www.gastrojournal.org/article/S0016-5085(13)00499-X/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/23583433?tool=bestpractice.com 美国食品药品监督管理局 (FDA) 已批准将其用于治疗以腹泻为主的 IBS。虽然之前艾沙度林可推荐用于切除胆囊的患者(低剂量应用),但 FDA 不再将其推荐用于这类患者,因有导致住院和死亡的胰腺炎病例报道。[47]US Food and Drug Administration. FDA drug safety communication: FDA warns about increased risk of serious pancreatitis with irritable bowel drug Viberzi (eluxadoline) in patients without a gallbladder. March 2017 [internet publication].https://www.fda.gov/Drugs/DrugSafety/ucm546154.htm 在英国,推荐艾沙度林在肠易激综合征伴腹泻患者中应用的条件是,只有当患者对其他药物治疗无反应或存在这些药物的禁忌证或不能耐受时;且从二级医疗机构才可开始应用。[48]National Institute for Health and Care Excellence. Eluxadoline for treating irritable bowel syndrome with diarrhoea. August 2017 [internet publication].https://www.nice.org.uk/guidance/ta471
腹痛或腹胀
有很多方式可治疗疼痛,包括以上提到的生活方式和饮食的改变。[49]Camilleri M, Boeckxstaens G. Dietary and pharmacological treatment of abdominal pain in IBS. Gut. 2017 May;66(5):966-74.http://www.ncbi.nlm.nih.gov/pubmed/28232472?tool=bestpractice.com 对于疼痛或腹胀患者的一线治疗应为解痉药。对于症状发作不频繁的患者,可规律使用或按需使用双环胺 (dicyclomine) 或莨菪碱 (hyoscyamine)。
薄荷油是具有解痉性能的古老制剂。已在一些研究中发现其有助于减轻 IBS 中的疼痛。[50]Pittler MH, Ernst E. Peppermint oil for irritable bowel syndrome: a critical review and meta analysis. Am J Gastroenterol. 1998 Jul;93(7):1131-5.http://www.ncbi.nlm.nih.gov/pubmed/9672344?tool=bestpractice.com[51]Ford AC,Talley NJ, Spiegel BM, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008 Nov 13;337:a2313.http://www.bmj.com/content/337/bmj.a2313.longhttp://www.ncbi.nlm.nih.gov/pubmed/19008265?tool=bestpractice.com 有滴剂或肠溶缓释片剂型。
如果使用解痉药后仍感疼痛,三环类抗抑郁药可能有帮助。[52]Rahimi R, Nikfar S, Rezaie A, et al. Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis. World J Gastroenterol. 2009 Apr 7;15(13):1548-53.http://www.wjgnet.com/1007-9327/full/v15/i13/1548.htmhttp://www.ncbi.nlm.nih.gov/pubmed/19340896?tool=bestpractice.com 然而,三环类抗抑郁药可能会引起便秘,因此,选择性5-羟色胺再摄取抑制(SSRIs),如帕罗西汀(paroxetine)或西酞普兰(citalopram)[53]Tack J, Broekaert D, Fischler B, et al. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006 Aug;55(8):1095-103.http://www.ncbi.nlm.nih.gov/pubmed/16401691?tool=bestpractice.com 对于便秘患者来说可能更合适。抑郁状态的患者也可考虑应用选择性 5-羟色胺再摄取抑制剂 (SSRIs)。然而,一项 Meta 分析质疑了使用选择性 5-羟色胺再摄取抑制剂治疗肠易激综合征的有效性。[54]Xie C, Tang Y, Wang Y, et al. Efficacy and safety of antidepressants for the treatment of irritable bowel syndrome: a meta-analysis. PLoS One. 2015 Aug 7;10(8):e0127815.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127815http://www.ncbi.nlm.nih.gov/pubmed/26252008?tool=bestpractice.com
而小部分对上述治疗措施均无反应的患者可能需要转诊,以获得更为强化的精神心理治疗与支持。催眠疗法和认知行为疗法已被证明有益于顽固性肠易激综合征患者。[55]Häuser W, Hagl M, Schmierer A, et al. The efficacy, safety and applications of medical hypnosis. Dtsch Arztebl Int. 2016 Apr 29;113(17):289-96.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873672/http://www.ncbi.nlm.nih.gov/pubmed/27173407?tool=bestpractice.com[56]Laird KT, Tanner-Smith EE, Russell AC, et al. Comparative efficacy of psychological therapies for improving mental health and daily functioning in irritable bowel syndrome: a systematic review and meta-analysis. Clin Psychol Rev. 2017 Feb;51:142-52.https://www.sciencedirect.com/science/article/pii/S0272735816300915http://www.ncbi.nlm.nih.gov/pubmed/27870997?tool=bestpractice.com[57]Radziwon CD, Lackner JM. Cognitive behavioral therapy for IBS: how useful, how often, and how does it work? Curr Gastroenterol Rep. 2017 Aug 17;19(10):49.http://www.ncbi.nlm.nih.gov/pubmed/28819814?tool=bestpractice.com[58]Windgassen S, Moss-Morris R, Chilcot J, et al. The journey between brain and gut: a systematic review of psychological mechanisms of treatment effect in irritable bowel syndrome. Br J Health Psychol. 2017 Nov;22(4):701-36.http://www.ncbi.nlm.nih.gov/pubmed/28573818?tool=bestpractice.com以腹痛相关症状为主的患者可能需要疼痛医师会诊或转诊至相关门诊。
利福昔明(rifaximn),一种几乎不为肠道吸收的抗生素,对没有便秘的IBS患者进行两周的治疗后,患者全身症状与腹胀都有一定改善。[59]Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22-32.http://www.nejm.org/doi/full/10.1056/NEJMoa1004409http://www.ncbi.nlm.nih.gov/pubmed/21208106?tool=bestpractice.com[60]Tack J. Antibiotic therapy for the irritable bowel syndrome. N Engl J Med. 2011 Jan 6;364(1):81-2.http://www.nejm.org/doi/full/10.1056/NEJMe1011211http://www.ncbi.nlm.nih.gov/pubmed/21208112?tool=bestpractice.com[61]Li J, Zhu W, Liu W, et al. Rifaximin for irritable bowel syndrome: a meta-analysis of randomized placebo-controlled trials. Medicine (Baltimore). 2016 Jan;95(4):e2534.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291563/http://www.ncbi.nlm.nih.gov/pubmed/26825893?tool=bestpractice.com这些研究均提示获益较小,且药物价格昂贵。因此,它无法作为一线治疗方案推荐,但可以作为难治性患者的辅助治疗。在某些国家,它已获准用于治疗以腹泻为主的肠易激综合征。