今日の臨床サポート

過敏性腸症候群

著者: 福土 審 東北大学大学院医学系研究科心療内科学・東北大学病院 心療内科

監修: 上村直実 国立国際医療研究センター 国府台病院

著者校正/監修レビュー済:2022/09/14
参考ガイドライン:
  1. 日本消化器病学会:日本消化器病学会機能性消化管疾患診療ガイドライン2020 ―過敏性腸症候群(IBS) (改訂第2版)
患者向け説明資料

概要・推奨   

  1. IBSの経過観察に臨床検査は有用である。(推奨度1)エビデンスレベルA
  1. IBSの治療に高分子重合体、食物繊維は有用である。(推奨度1)エビデンスレベルA
  1. IBSにプロバイオティクスは有用である。(推奨度1)エビデンスレベルA
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  1. IBS-Dの治療に5-HT3拮抗薬は有用である。(推奨度1)エビデンスレベルA
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
福土 審 : 未申告[2022年]
監修:上村直実 : 未申告[2022年]

改訂のポイント:
  1. 日本消化器病学会IBS診療ガイドラインに基づき、記載全般について改訂を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 過敏性腸症候群(irritable bowel syndrome: IBS)とは、慢性の腹痛が下痢や便秘など便通の異常と関連して持続し、通常検査では癌や潰瘍性病変などの器質的病変を欠く疾患である。主として大腸・小腸の運動、知覚、粘膜透過性、分泌の異常と脳腸相関が増強した機能障害である。
  1. わが国における過敏性腸症候群の有病率は人口の14.2%、1年間の罹患率は1~2%、内科外来患者の31%と高頻度である。女性にやや多く、男女比は日本では1:2である。また、20~30代の若年成人で頻度が高く、その後次第に減少する。ほかに高学歴であると罹患率が高く、身体不安やうつ状態を測定した尺度が高い患者でも罹患率が高い。
  1. 診断については、2016年に公刊されたRome IV基準が国際的に使用されている[1]。Rome IV基準ではIBSを腹痛を有する典型的患者だけに絞ったため、有病率は世界人口の4.1%(日本では2.2%)、男女比1:1.7であった[2]
 
過敏性腸症候群(IBS)のRome IV診断基準

他疾患が否定されれば、機能性消化管障害(functional gastrointestinal disorder、FGID)であり、Rome IV基準に基づいてIBSを診断する。IBSは、Bristol便形状尺度(<図表>)に基づいて4型に便宜的に分類する(<図表>)。Rome IVのIBS診断基準を満たさなければ、IBS以外のFGIDである。腹痛のない便秘は機能性便秘、腹痛のない下痢は機能性下痢、便通異常のない腹痛は機能性腹痛症候群、便通異常のない腹部膨満感は機能性腹部膨満、いずれでもなければ非特異機能性腸疾患である。Rome IVは2016年に公刊された。

出典

img1:  Bowel Disorders.
 
 Gastroenterology. 2016 Feb 18;. doi: 10.・・・
 
  1. IBSの主要病態生理は消化管運動異常、内臓知覚過敏、心理的異常の3つであるが、これらは脳腸相関(brain–gut interaction)によって相互に関連しており、ストレスによる症状の発症・増悪も顕著である[3]
  1. IBSの成因はいまだ不明だが、感染性腸炎後IBSの一群の存在から、腸内細菌の関与が着目されている。
  1. 治療については、わが国の医療に沿った日本消化器病学会による診断・治療ガイドラインが公表されている[3]。Rome委員会でも治療アルゴリズムが考案されている[4]
  1. 過敏性腸症候群(IBS)の診断フローチャート:アルゴリズム
  1. 過敏性腸症候群(IBS)の治療:第1段階:アルゴリズム
  1. 過敏性腸症候群(IBS)の治療:第2段階:アルゴリズム
  1. 過敏性腸症候群(IBS)の治療:第3段階:アルゴリズム
問診・診察のポイント  
  1. 腹痛が、最近3カ月のなかの1週間につき少なくとも1日以上は生じる。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

Fermín Mearin, Brian E Lacy, Lin Chang, William D Chey, Anthony J Lembo, Magnus Simren, Robin Spiller
Bowel Disorders.
Gastroenterology. 2016 Feb 18;. doi: 10.1053/j.gastro.2016.02.031. Epub 2016 Feb 18.
Abstract/Text Functional bowel disorders are highly prevalent disorders found worldwide. These disorders have the potential to affect all members of society, regardless of age, gender, race, creed, color or socioeconomic status. Improving our understanding of functional bowel disorders (FBD) is critical as they impose a negative economic impact to the global health care system in addition to reducing quality of life. Research in the basic and clinical sciences during the past decade has produced new information on the epidemiology, etiology, pathophysiology, diagnosis and treatment of FBDs. These important findings created a need to revise the Rome III criteria for FBDs, last published in 2006. This manuscript classifies the FBDs into five distinct categories: irritable bowel syndrome (IBS); functional constipation (FC); functional diarrhea (FDr); functional abdominal bloating/distention (FAB/D); and unspecified FBD (U-FBD). Also included in this article is a new sixth category, opioid induced constipation (OIC) which is distinct from the functional bowel disorders (FBDs). Each disorder will first be defined, followed by sections on epidemiology, rationale for changes from prior criteria, clinical evaluation, physiologic features, psychosocial features and treatment. It is the hope of this committee that this new information will assist both clinicians and researchers in the decade to come.

Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 27144627
Ami D Sperber, Shrikant I Bangdiwala, Douglas A Drossman, Uday C Ghoshal, Magnus Simren, Jan Tack, William E Whitehead, Dan L Dumitrascu, Xuicai Fang, Shin Fukudo, John Kellow, Edith Okeke, Eamonn M M Quigley, Max Schmulson, Peter Whorwell, Timothy Archampong, Payman Adibi, Viola Andresen, Marc A Benninga, Bruno Bonaz, Serhat Bor, Luis Bustos Fernandez, Suck Chei Choi, Enrico S Corazziari, Carlos Francisconi, Albis Hani, Leonid Lazebnik, Yeong Yeh Lee, Agata Mulak, M Masudur Rahman, Javier Santos, Mashiko Setshedi, Ari Fahrial Syam, Stephen Vanner, Reuben K Wong, Aurelio Lopez-Colombo, Valeria Costa, Ram Dickman, Motoyori Kanazawa, Ammar Hassanzadeh Keshteli, Rutaba Khatun, Iradj Maleki, Pierre Poitras, Nitesh Pratap, Oksana Stefanyuk, Sandie Thomson, Judith Zeevenhooven, Olafur S Palsson
Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.
Gastroenterology. 2021 Jan;160(1):99-114.e3. doi: 10.1053/j.gastro.2020.04.014. Epub 2020 Apr 12.
Abstract/Text BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents.
METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately.
RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%).
CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
PMID 32294476
Shin Fukudo, Toshikatsu Okumura, Masahiko Inamori, Yusuke Okuyama, Motoyori Kanazawa, Takeshi Kamiya, Ken Sato, Akiko Shiotani, Yuji Naito, Yoshiko Fujikawa, Ryota Hokari, Tastuhiro Masaoka, Kazuma Fujimoto, Hiroshi Kaneko, Akira Torii, Kei Matsueda, Hiroto Miwa, Nobuyuki Enomoto, Tooru Shimosegawa, Kazuhiko Koike
Evidence-based clinical practice guidelines for irritable bowel syndrome 2020.
J Gastroenterol. 2021 Mar;56(3):193-217. doi: 10.1007/s00535-020-01746-z. Epub 2021 Feb 4.
Abstract/Text Managing irritable bowel syndrome (IBS) has attracted international attention because single-agent therapy rarely relieves bothersome symptoms for all patients. The Japanese Society of Gastroenterology (JSGE) published the first edition of evidence-based clinical practice guidelines for IBS in 2015. Much more evidence has accumulated since then, and new pharmacological agents and non-pharmacological methods have been developed. Here, we report the second edition of the JSGE-IBS guidelines comprising 41 questions including 12 background questions on epidemiology, pathophysiology, and diagnostic criteria, 26 clinical questions on diagnosis and treatment, and 3 questions on future research. For each question, statements with or without recommendations and/or evidence level are given and updated diagnostic and therapeutic algorithms are provided based on new evidence. Algorithms for diagnosis are requisite for patients with chronic abdominal pain or associated symptoms and/or abnormal bowel movement. Colonoscopy is indicated for patients with one or more alarm symptoms/signs, risk factors, and/or abnormal routine examination results. The diagnosis is based on the Rome IV criteria. Step 1 therapy consists of diet therapy, behavioral modification, and gut-targeted pharmacotherapy for 4 weeks. For non-responders, management proceeds to step 2 therapy, which includes a combination of different mechanistic gut-targeted agents and/or psychopharmacological agents and basic psychotherapy for 4 weeks. Step 3 therapy is for non-responders to step 2 and comprises a combination of gut-targeted pharmacotherapy, psychopharmacological treatments, and/or specific psychotherapy. These updated JSGE-IBS guidelines present best practice strategies for IBS patients in Japan and we believe these core strategies can be useful for IBS diagnosis and treatment globally.

PMID 33538894
Heather A Halvorson, Carey D Schlett, Mark S Riddle
Postinfectious irritable bowel syndrome--a meta-analysis.
Am J Gastroenterol. 2006 Aug;101(8):1894-9; quiz 1942. doi: 10.1111/j.1572-0241.2006.00654.x.
Abstract/Text OBJECTIVES: Irritable bowel syndrome (IBS) is a heterogeneous disorder affecting 12% of the population worldwide. Several studies identify IBS as a sequela of infectious gastroenteritis (IGE) with reported prevalence ranging from 4% to 31% and relative risk from 2.5 to 11.9. This meta-analysis was conducted to explore the differences between reported rates and provide a pooled estimate of risk for postinfectious irritable bowel syndrome (PI-IBS).
DATA SOURCES: Electronic databases (MEDLINE, OLDMEDLINE, EMBASE, Cochrane database of clinical trials) and pertinent reference lists (including other review articles).
REVIEW METHODS: Data were abstracted from included studies by two independent investigators; study quality, heterogeneity, and publication bias were assessed; sensitivity analysis was performed; and a summative effect estimate was calculated for risk of PI-IBS.
RESULTS: Eight studies were included for analysis and all reported elevated risk of IBS following IGE. Median prevalence of IBS in the IGE groups was 9.8% (IQR 4.0-13.3) and 1.2% in control groups (IQR 0.4-1.8) (sign-rank test, p= 0.01). The pooled odds ratio was 7.3 (95% CI, 4.7-11.1) without significant heterogeneity (chi2 heterogeneity statistic, p= 0.41). Subgroup analysis revealed an association between PI-IBS risk and IGE definition used.
CONCLUSIONS: This study provides supporting evidence for PI-IBS as a sequela of IGE and a pooled risk estimate revealing a sevenfold increase in the odds of developing IBS following IGE. The results suggest that the long-term benefit of reduced PI-IBS may be gained from primary prevention of IGE.

PMID 16928253
M Thabane, D T Kottachchi, J K Marshall
Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome.
Aliment Pharmacol Ther. 2007 Aug 15;26(4):535-44. doi: 10.1111/j.1365-2036.2007.03399.x.
Abstract/Text BACKGROUND: Individual studies suggest that post-infectious irritable bowel syndrome is common, but symptoms gradually improve.
AIM: To review evidence for an association between intestinal infection and development of irritable bowel syndrome, assess the prognosis of post-infectious irritable bowel syndrome and explore factors that increase the risk.
METHODS: MEDLINE (1966-2007) and EMBASE (1980-2007) databases were searched to identify the studies of post-infectious irritable bowel syndrome epidemiology. Data were extracted by two independent reviewers. Pooled odds ratios (POR) and corresponding 95% CI for incidence of irritable bowel syndrome were estimated among the exposed and unexposed groups.
RESULTS: Eighteen of 26 studies identified were eligible for inclusion. Intestinal infection was associated with increased odds of developing irritable bowel syndrome at study end (POR = 5.86; 95% CI: 3.60-9.54). In subgroup analysis, the odds of developing irritable bowel syndrome was increased at 3 months (POR = 7.58; 95% CI: 4.27-13.45), 6 months (POR = 5.18; 95% CI: 3.24-8.26), 12 months (POR = 6.37; 95% CI: 2.63-15.40) and 24-36 months (POR = 3.85; 95% CI: 2.95-5.02). Among all studies (controlled and uncontrolled), the pooled incidence of irritable bowel syndrome at study conclusion was 10% (95% CI: 9.4-85.6). Subjects with post-infectious irritable bowel syndrome were younger and more anxious and depressed than those without post-infectious irritable bowel syndrome.
CONCLUSION: The odds of developing irritable bowel syndrome are increased sixfold after acute gastrointestinal infection. Young age, prolonged fever, anxiety and depression are risk factors for post-infectious irritable bowel syndrome.

PMID 17661757
Stacy B Menees, Corey Powell, Jacob Kurlander, Akash Goel, William D Chey
A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS.
Am J Gastroenterol. 2015 Mar;110(3):444-54. doi: 10.1038/ajg.2015.6. Epub 2015 Mar 3.
Abstract/Text OBJECTIVES: Irritable bowel syndrome (IBS) is viewed as a diagnosis of exclusion by most providers. The aim of our study was to perform a systematic review and meta-analysis to evaluate the utility of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and fecal lactoferrin to distinguish between patients with IBS and inflammatory bowel disease (IBD) and healthy controls (HCs).
METHODS: A systematic online database search was performed. Included studies were prospective, adult, diagnostic cohort studies with any of the four tests. The means and s.d. values of biomarker logarithms were estimated based on studies that gave medians and either confidence intervals for the median, interquartile ranges, or ranges. We used a Naive Bayes approach to estimate the probability of being a HC, having IBS, or having IBD based on the biomarker values.
RESULTS: Systematic review identified 1,252 citations. After cross-referencing medical subject headings, detailed evaluation identified 140 potentially relevant journal articles/abstracts for CRP, ESR, calprotectin, and lactoferrin of which 4, 4, 8, and 2 fulfilled our inclusion criteria, respectively. None of the biomarkers reliably distinguished between IBS and healthy controls. At a CRP level of ≤0.5 or calprotectin level of ≤40 μg/g, there was a ≤1% probability of having IBD. Individual analysis of ESR and lactoferrin had little clinical utility.
CONCLUSION: CRP and calprotectin of ≤0.5 or 40, respectively, essentially excludes IBD in patients with IBS symptoms. The addition of CRP and calprotectin to symptom-based criteria may improve the confident diagnosis of IBS.

PMID 25732419
George F Longstreth, W Grant Thompson, William D Chey, Lesley A Houghton, Fermin Mearin, Robin C Spiller
Functional bowel disorders.
Gastroenterology. 2006 Apr;130(5):1480-91. doi: 10.1053/j.gastro.2005.11.061.
Abstract/Text Employing a consensus approach, our working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations. Diagnosis of a functional bowel disorder (FBD) requires characteristic symptoms during the last 3 months and onset > or =6 months ago. Alarm symptoms suggest the possibility of structural disease, but do not necessarily negate a diagnosis of an FBD. Irritable bowel syndrome (IBS), functional bloating, functional constipation, and functional diarrhea are best identified by symptom-based approaches. Subtyping of IBS is controversial, and we suggest it be based on stool form, which can be aided by use of the Bristol Stool Form Scale. Diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. Treatment of FBDs is based on an individualized evaluation, explanation, and reassurance. Alterations in diet, drug treatment aimed at predominant symptoms, and psychotherapy may be beneficial.

PMID 16678561
Douglas A Drossman, Carolyn B Morris, Yuming Hu, Brenda B Toner, Nicholas Diamant, Jane Leserman, Michael Shetzline, Christine Dalton, Shrikant I Bangdiwala
A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator.
Gastroenterology. 2005 Mar;128(3):580-9.
Abstract/Text BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is subtyped as IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C) based on Rome II guidelines. The remaining group is considered as having mixed IBS (IBS-M). There is no standard definition of an alternator (IBS-A), in which bowel habit changes over time. Our aim was to use Rome II criteria to prospectively assess change in bowel habit for more than 1 year to understand IBS-A.
METHODS: Female patients (n=317) with IBS entering a National Institutes of Health treatment trial were studied at baseline with questionnaires and 2-week daily diary cards of pain and stool frequency and consistency. Studies were repeated at the end of treatment (3 months) and at four 3-month intervals for one more year. Algorithms to classify subjects into IBS-D, IBS-C, and IBS-M groups used diary card information and modified Rome II definitions. Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures.
RESULTS: At baseline, 36% had IBS-D, 31% IBS-M, and 34% IBS-C. Except for stool frequency, there were no differences between groups. While the proportion of subjects in each subgroup remained the same over the year, most individuals (more than 75%) changed to either of the other 2 subtypes at least once. IBS-M was the least stable (50% changed out by 12 weeks). Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably, only 29% switched between the IBS-D and IBS-C subtypes over the year.
CONCLUSIONS: While the proportion of subjects in each of the IBS subtypes stays the same, individuals commonly transition between subtypes, particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period.

PMID 15765393
William E Whitehead, Olafur Palsson, Kenneth R Jones
Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?
Gastroenterology. 2002 Apr;122(4):1140-56.
Abstract/Text BACKGROUND & AIMS: Comorbid or extraintestinal symptoms occur frequently with irritable bowel syndrome and account for up to three fourths of excess health care visits. This challenges the assumption that irritable bowel is a distinct disorder. The aims of this study were to (1) assess comorbidity in 3 areas: gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders; and (2) evaluate explanatory hypotheses.
METHODS: The scientific literature since 1966 in all languages cited in Medline was systematically reviewed.
RESULTS: Comorbidity with other functional gastrointestinal disorders is high and may be caused by shared pathophysiological mechanisms such as visceral hypersensitivity. Psychiatric disorders, especially major depression, anxiety, and somatoform disorders, occur in up to 94%. The nongastrointestinal nonpsychiatric disorders with the best-documented association are fibromyalgia (median of 49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%).
CONCLUSIONS: Multivariate statistical analyses suggest that these are distinct disorders and not manifestations of a common somatization disorder, but their strong comorbidity suggests a common feature important to their expression, which is most likely psychological. Some models explain the comorbidity of irritable bowel with other disorders by suggesting that each disorder is the manifestation of varying combinations of interacting physiological and psychological factors. An alternative hypothesis is that the irritable bowel diagnosis is applied to a heterogeneous group of patients, some of whom have a predominantly psychological etiology, whereas others have a predominantly biological etiology, and that the presence of multiple comorbid disorders is a marker for psychological influences on etiology.

PMID 11910364
C Y Francis, J Morris, P J Whorwell
The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress.
Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x.
Abstract/Text BACKGROUND: The clinical assessment and investigation of irritable bowel syndrome would be greatly facilitated by the introduction of a simple, easy to use severity scoring system. Such a system, developed in our department over a number of years, has been submitted to validation in a total of 141 patients and 40 healthy controls.
METHODS: The system, incorporating pain, distension, bowel dysfunction and quality of life/global well-being, was assessed for its ability to reliably score patients previously classified as mild, moderate or severe. The reproducibility and sensitivity to change of the system was also assessed.
RESULTS: The maximum achievable score was 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and > 300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission. There was a highly significant difference between controls and patients as a whole (P = 0.0001) as well as significant differences (P < 0.01) between all severity categories. Scores repeated within 24 h were very reproducible and sensitivity to change was also extremely good (P < 0.001) with a change of 50 reliably indicating improvement.
CONCLUSION: These results suggest that this scoring system should prove to be a valuable instrument in helping to meet the many challenges offered by irritable bowel syndrome.

PMID 9146781
Masae Shinozaki, Motoyori Kanazawa, Yasuhiro Sagami, Yuka Endo, Michio Hongo, Douglas A Drossman, William E Whitehead, Shin Fukudo
Validation of the Japanese version of the Rome II modular questionnaire and irritable bowel syndrome severity index.
J Gastroenterol. 2006 May;41(5):491-4. doi: 10.1007/s00535-006-1799-9.
Abstract/Text BACKGROUND: Instruments for measuring the presence and severity of specific irritable bowel syndrome (IBS) symptoms, comparable to those used in Western countries, have been lacking in Japan. The aim of this study was to develop, validate, and confirm the reliability of the Japanese version of the Rome II modular questionnaire for IBS (RIIMQ-J) and the IBS severity index (IBSSI-J).
METHODS: Forty-nine patients in the university hospital with chronic or recurrent abdominal pain and discomfort and/or altered bowel habits were enrolled. With Rome II criteria, 27 patients were diagnosed as having IBS, and the other 22 patients were evaluated as having other functional bowel disorders (FBDs). The English versions of RIIMQ and IBSSI were translated into Japanese. After back-translation and approval of the questionnaire, subjects completed both questionnaires twice within 14 days.
RESULTS: Cronbach's alpha of the RIIMQ-J was high (0.72). The sensitivity of RIIMQ-J for the diagnosis of IBS was also high (89%). The specificity of RIIMQ-J for denial of IBS among patients with other FBD was satisfactory (73%). The IBSSI-J showed high internal consistency (0.69) and reproducibility (intraclass correlation coefficient, 0.86, P < 0.001).
CONCLUSIONS: The RIIMQ-J and IBSSI-J are valid, reliable, and appropriate instruments for detecting and assessing the severity of IBS status in Japanese patients.

PMID 16799892
D A Drossman, Z Li, B B Toner, N E Diamant, F H Creed, D Thompson, N W Read, C Babbs, M Barreiro, L Bank
Functional bowel disorders. A multicenter comparison of health status and development of illness severity index.
Dig Dis Sci. 1995 May;40(5):986-95.
Abstract/Text In a multicenter study of patients with painful functional bowel disorders (FBD), we compared the demographic, health status, and diagnostic features of patients with FBD and developed a functional bowel disorder severity index (FBDSI) for research and clinical care. Two hundred seventy patients with FBD in the United States, England, and Canada were surveyed on symptoms and health status, and their physicians made a diagnosis and rated illness severity as mild, moderate, or severe. Comparisons of 22 demographic and clinical variables were made by study site in addition to physicians' severity ratings. To develop the FBDSI, multiple regression analysis used the demographic and clinical variables to predict the physician's rating of severity. We found that most health status measures of patients with FBD across study sites are comparable and the derived and validated FBDSI scoring system uses three easy to obtain variables: FBDSI = [current pain by visual analog scale (0-100)] + [diagnosis of chronic functional abdominal pain (0 if absent and 106 if present)] + [number of physicians visits over previous six months x 11]. The FBDSI can be used to select patients for research protocols and/or follow their clinical outcome or response to treatments over time.

PMID 7729289
Smita L S Halder, G Richard Locke, Cathy D Schleck, Alan R Zinsmeister, L Joseph Melton, Nicholas J Talley
Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study.
Gastroenterology. 2007 Sep;133(3):799-807. doi: 10.1053/j.gastro.2007.06.010. Epub 2007 Jun 20.
Abstract/Text BACKGROUND & AIMS: Functional gastrointestinal disorders (FGID) are common in the community. The natural history of FGID is unknown because of a lack of prospective population-based studies and the indistinct nature of the phenotype. We sought to report the natural history of FGID in a US population.
METHODS: This prospective cohort study used data from multiple validated surveys of random samples of Olmsted County, MN, residents over a mean of a 12-year period between 1988 and 2003 (n = 1365). The surveys measured gastrointestinal symptoms experienced during the past year. Each subject received a minimum of 2 surveys. Point prevalence, onset, and disappearance rates and transition probabilities were calculated for individual FGIDs.
RESULTS: Between the initial and final surveys, the point prevalences (per 100 residents) were stable for irritable bowel syndrome (8.3% and 11.4%, respectively) and functional dyspepsia (1.9% and 3.3%, respectively). The onset of each of the disorders studied was greater than the disappearance rate, but the transition probabilities varied across the different subgroups. Among people with symptoms at baseline, approximately 20% had the same symptoms, 40% had no symptoms, and 40% had different symptoms at follow-up.
CONCLUSIONS: Although the prevalence of the FGID was stable over time, the turnover in symptom status was high. Many episodes of symptom disappearance were due to subjects changing symptoms rather than total symptom resolution. This transition between different FGIDs suggests a common etiopathogenesis.

PMID 17678917
D M Owens, D K Nelson, N J Talley
The irritable bowel syndrome: long-term prognosis and the physician-patient interaction.
Ann Intern Med. 1995 Jan 15;122(2):107-12.
Abstract/Text OBJECTIVE: To evaluate the long-term course and prognosis associated with the irritable bowel syndrome (IBS) and to determine the influence of an effective physician-patient relationship on subsequent health care use.
DESIGN: Prospective review of medical records.
SETTING: Tertiary referral center.
PATIENTS: 112 consecutive Olmsted County, Minnesota, residents who were first diagnosed with IBS at the Mayo Clinic during the period 1961-1963.
RESULTS: The median follow-up was 29 years (range, 1 to 32 years) and patients made a median of 2 return visits for IBS-related symptoms (range, 0 to 12 visits). In addition to abdominal pain, diarrhea (reported by 50% of patients) was the predominant bowel symptom at diagnosis. Organic gastrointestinal disease occurred in 10 patients a median of 15 years after diagnosis of IBS. Survival in patients with IBS did not differ from expected survival (27 deaths; median survival > 30 years after initial diagnosis). A positive physician-patient interaction, defined a priori using objective criteria in the written record, was associated with fewer return visits for IBS. Of the eight variables examined, notations in the medical record about psychosocial history, precipitating factors, and discussion of diagnosis and treatment with patients were associated with fewer return visits for IBS-related symptoms.
CONCLUSIONS: When diagnosed according to current criteria, IBS is associated with a good prognosis and the diagnosis is unlikely to be changed to that of an organic disease during follow-up. A positive physician-patient interaction may be related to reduced use of ambulatory health services by patients with IBS.

PMID 7992984
D A Drossman, W G Thompson
The irritable bowel syndrome: review and a graduated multicomponent treatment approach.
Ann Intern Med. 1992 Jun 15;116(12 Pt 1):1009-16.
Abstract/Text The irritable bowel syndrome is a common chronic disorder having a broad clinical spectrum of severity. Although only a small proportion of those afflicted seek medical help for their symptoms, a subset have severe and intractable symptoms. A positive diagnosis should be established from the history and physical examination; endoscopic and radiologic investigations should be minimized. We suggest that the physician also assess the severity of the illness based on its symptomatic and functional features and the patient's behavioral response. Classifying the disorder in this manner permits a graduated treatment approach that emphasizes education, reassurance, and dietary adjustment for mild symptoms. Moderate symptom severity requires, in addition, identification and modification of factors exacerbating symptoms, psychotherapeutic and behavioral techniques and, if a certain symptom type predominates, pharmacologic agents directed toward the presumed gastrointestinal motor dysfunction. For severe symptoms, physician-based behavior modification and psychopharmacologic agents are helpful. When the disorder is intractable, referral may be needed, for example, to a pain treatment center. In all cases, the skillful physician must ensure continued psychosocial support to enhance coping and continued focus on the palliative aspects of care rather than on cure.

PMID 1586090
Ted J Kaptchuk, John M Kelley, Lisa A Conboy, Roger B Davis, Catherine E Kerr, Eric E Jacobson, Irving Kirsch, Rosa N Schyner, Bong Hyun Nam, Long T Nguyen, Min Park, Andrea L Rivers, Claire McManus, Efi Kokkotou, Douglas A Drossman, Peter Goldman, Anthony J Lembo
Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome.
BMJ. 2008 May 3;336(7651):999-1003. doi: 10.1136/bmj.39524.439618.25. Epub 2008 Apr 3.
Abstract/Text OBJECTIVE: To investigate whether placebo effects can experimentally be separated into the response to three components-assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship-and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components.
DESIGN: A six week single blind three arm randomised controlled trial.
SETTING: Academic medical centre.
PARTICIPANTS: 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of > or =150 on the symptom severity scale.
INTERVENTIONS: For three weeks either waiting list (observation), placebo acupuncture alone ("limited"), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence ("augmented"). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks.
MAIN OUTCOME MEASURES: Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life.
RESULTS: At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus "limited" versus "augmented," respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01). Results were similar at six week follow-up.
CONCLUSION: Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.
TRIAL REGISTRATION: Clinical Trials NCT00065403.

PMID 18390493
Maria Pia Caldarella, Angelo Milano, Francesco Laterza, Flora Sacco, Crysanthi Balatsinou, Domenico Lapenna, Sante Donato Pierdomenico, Franco Cuccurullo, Matteo Neri
Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant irritable bowel syndrome (IBS): effect of a low-fat intraduodenal infusion.
Am J Gastroenterol. 2005 Feb;100(2):383-9. doi: 10.1111/j.1572-0241.2005.40100.x.
Abstract/Text BACKGROUND: Visceral hypersensitivity is common in Irritable Bowel Syndrome (IBS) patients, and symptoms exacerbate postprandially. Yet the effects of nutrients on visceral sensitivity and symptoms in these patients have not been fully explored.
AIMS: To evaluate the differences of visceral sensitivity and symptoms in healthy subjects and IBS patients during fasting and intraduodenal lipids infusion.
METHODS: Graded rectal distensions at fixed tension levels were performed in 16 IBS patients (8 IBS-C and 8 IBS-D) and 6 healthy subjects before and during intraduodenal lipids infusion at 0.5 kcal/min. Tension levels were increased in 4 gr increments up to 64 gr or discomfort during both conditions. At each step, perception and symptoms were measured by means of a validated questionnaire.
RESULTS: In basal conditions, perception thresholds in IBS patients and health were, respectively, 8 +/- 2 gr versus 32 +/- 9 gr (p < 0.001) with no changes during lipids. Intraduodenal lipids infusion significantly lowered threshold of discomfort in IBS patients in comparison to fasting (24 +/- 6 gr vs 34 +/- 4 gr; p < 0.05), while health tolerated all distension without discomfort. No differences of compliance, perception, or discomfort were observed between the two subgroups of patients at each tension step. The predominant symptom elicited in patients with IBS-C was abdominal pain (54%), while patients with IBS-D exhibited urgency (63%, p < 0.005); this pattern was maintained during lipids.
CONCLUSIONS: Intraduodenal lipids increase visceral sensitivity in both IBS-C and IBS-D; symptoms specificity in response to rectal distension is maintained in the postprandial period. Lipids may be responsible for the postprandial symptoms exacerbation in IBS.

PMID 15667496
Yasuhiro Fujiwara, Makiko Kubo, Yukie Kohata, Hirohisa Machida, Hirotoshi Okazaki, Hirokazu Yamagami, Tetsuya Tanigawa, Kenji Watanabe, Toshio Watanabe, Kazunari Tominaga, Tetsuo Arakawa
Cigarette smoking and its association with overlapping gastroesophageal reflux disease, functional dyspepsia, or irritable bowel syndrome.
Intern Med. 2011;50(21):2443-7. Epub 2011 Nov 1.
Abstract/Text BACKGROUND: Gastroesophageal reflux disease (GERD), functional dyspepsia (FD), and irritable bowel syndrome (IBS) are common gastrointestinal diseases. Several studies have shown a significant occurrence of overlap among these 3 diseases. The purpose of this study was to examine the factors associated with such disease overlap in Japanese adults.
METHODS: We performed a cross-sectional study on Japanese workers who visited a clinic for a routine health check-up and asked them to fill out a self-report questionnaire. GERD was defined as episodes of heartburn and/or acid regurgitation at least once a week, and the diagnosis of FD and IBS was based on Rome III criteria. A logistic regression model was used to identify risk factors, and odds ratio (OR) was calculated with 95% confidence intervals (CIs).
RESULTS: Disease overlaps were found in 160 (6.0%) of the 2680 eligible subjects. Female gender was associated with GERD + IBS (OR=1.99; 95% CI, 1.06-3.75), and FD + IBS (OR=1.72; 95% CI, 1.03-2.85), and lower body mass index was negatively associated with FD + IBS (OR=0.54; 96% CI, 0.34-0.87). Cigarette smoking was a common factor associated with the overlaps: GERD + FD (OR=2.14; 95% CI, 1.22-3.76), GERD + IBS (OR=3.16; 95% CI, 1.75-3.71), FD + IBS (OR=2.26; 95% CI, 1.40-3.66), and GERD + FD + IBS (OR=4.08; 95% CI, 1.66-10.07). The associations between smoking habits and overlaps were stronger in smokers who smoked ≥1 pack per day as compared to those who smoked <1 pack per day.
CONCLUSION: Cigarette smoking was significantly associated with overlaps among GERD, FD, and IBS in Japanese adults.

PMID 22041340
G R Locke, A R Zinsmeister, N J Talley, S L Fett, L J Melton
Risk factors for irritable bowel syndrome: role of analgesics and food sensitivities.
Am J Gastroenterol. 2000 Jan;95(1):157-65. doi: 10.1111/j.1572-0241.2000.01678.x.
Abstract/Text OBJECTIVE: Symptoms of irritable bowel syndrome (IBS) are reported by 10% of the general population; however, evaluation of traditional risk factors has not provided any insight into the pathogenesis of this condition. The objective of this study was to identify additional risk factors for irritable bowel syndrome.
METHODS: A valid self-report questionnaire that records the gastrointestinal (GI) symptoms required for a diagnosis of IBS, self-reported measures of potential risk factors, and a psychosomatic symptom checklist was mailed to an age-and gender-stratified random sample of Olmsted County, Minnesota residents aged 30-64 yr. A logistic regression model that adjusted for age, gender, and psychosomatic symptom score was used to identify factors significantly associated with IBS.
RESULTS: A total of 643 (72%) of 892 eligible subjects returned the survey. IBS symptoms were reported by 12% of the respondents. IBS was significantly associated with use of analgesics (acetaminophen, aspirin, or nonaspirin nonsteroidal antiinflammatory drugs) for reasons other than IBS, reporting a food allergy or sensitivity, and ratings of somatic symptoms. No association was detected for age, gender, body mass index, smoking history, alcohol use, educational level, exposure to pets in the household, or water supply. Among subjects reporting the use of just one type of analgesic, IBS was associated with acetaminophen but not aspirin or nonaspirin nonsteroidal antiinflammatory drugs used alone. The odds of having IBS were higher among subjects reporting more reasons for taking analgesics and intolerance to a higher number of foods.
CONCLUSIONS: IBS is significantly associated with analgesic use. However, this is confounded by other somatic pain complaints. IBS symptoms are associated with the reporting of many food allergies or sensitivities. The role of food-induced symptoms in IBS requires further investigation.

PMID 10638576
Elisabet Johannesson, Magnus Simrén, Hans Strid, Antal Bajor, Riadh Sadik
Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial.
Am J Gastroenterol. 2011 May;106(5):915-22. doi: 10.1038/ajg.2010.480. Epub 2011 Jan 4.
Abstract/Text OBJECTIVES: Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS.
METHODS: We randomized 102 patients to a physical activity group and a control group. Patients of the physical activity group were instructed by a physiotherapist to increase their physical activity, and those of the control group were instructed to maintain their lifestyle. The primary end point was to assess the change in the IBS Severity Scoring System (IBS-SSS).
RESULTS: A total of 38 (73.7% women, median age 38.5 (19-65) years) patients in the control group and 37 (75.7% women, median age 36 (18-65) years) patients in the physical activity group completed the study. There was a significant difference in the improvement in the IBS-SSS score between the physical activity group and the control group (-51 (-130 and 49) vs. -5 (-101 and 118), P=0.003). The proportion of patients with increased IBS symptom severity during the study was significantly larger in the control group than in the physical activity group.
CONCLUSIONS: Increased physical activity improves GI symptoms in IBS. Physically active patients with IBS will face less symptom deterioration compared with physically inactive patients. Physical activity should be used as a primary treatment modality in IBS.

PMID 21206488
Leora Kuttner, Christine T Chambers, Janine Hardial, David M Israel, Kevan Jacobson, Kathy Evans
A randomized trial of yoga for adolescents with irritable bowel syndrome.
Pain Res Manag. 2006 Winter;11(4):217-23.
Abstract/Text BACKGROUND: Adolescents with irritable bowel syndrome (IBS) frequently experience interference with everyday activities. Mind-body approaches such as yoga have been recommended as interventions for patients with IBS. Despite promising results among adult samples, there have been limited studies exploring the efficacy of yoga with pediatric patients.
OBJECTIVE: To conduct a preliminary randomized study of yoga as treatment for adolescents with IBS.
METHODS: Twenty-five adolescents aged 11 to 18 years with IBS were randomly assigned to either a yoga or wait list control group. Before the intervention, both groups completed questionnaires assessing gastrointestinal symptoms, pain, functional disability, coping, anxiety and depression. The yoga intervention consisted of a 1 h instructional session, demonstration and practice, followed by four weeks of daily home practice guided by a video. After four weeks, adolescents repeated the baseline questionnaires. The wait list control group then received the yoga intervention and four weeks later completed an additional set of questionnaires.
RESULTS: Adolescents in the yoga group reported lower levels of functional disability, less use of emotion-focused avoidance and lower anxiety following the intervention than adolescents in the control group. When the pre- and postintervention data for the two groups were combined, adolescents had significantly lower scores for gastrointestinal symptoms and emotion-focused avoidance following the yoga intervention. Adolescents found the yoga to be helpful and indicated they would continue to use it to manage their IBS.
CONCLUSIONS: Yoga holds promise as an intervention for adolescents with IBS.

PMID 17149454
A J Daley, C Grimmett, L Roberts, S Wilson, M Fatek, A Roalfe, S Singh
The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial.
Int J Sports Med. 2008 Sep;29(9):778-82. doi: 10.1055/s-2008-1038600. Epub 2008 May 6.
Abstract/Text While it seems intuitively appealing to promote participation in regular exercise in the management of irritable bowel syndrome, limited randomised controlled trial evidence exists to support this recommendation. We examined the feasibility and effects of an exercise intervention upon quality of life and irritable bowel symptoms using a randomised controlled trial methodology. Patients with a clinically confirmed diagnosis of irritable bowel syndrome according to Rome II criteria were randomised to either an exercise consultation intervention or usual care for 12 weeks. Outcomes included irritable bowel specific quality of life, symptoms (total symptoms, constipation, diarrhoea and pain) and exercise participation. The recruitment rate of eligible patients identified from hospital records was 18.3% (56/305). Analyses revealed no differences in quality life scores between groups at 12-week follow-up. The exercise group reported significantly improved symptoms of constipation (mean difference=10.9, 95 % CI= -20.1, -1.6) compared to usual care at follow-up. The intervention group participated in significantly more exercise than usual care at follow-up (mean difference=21.6, 95% CI=9.4, 33.8). Recruitment of eligible patients into this study was possible but rates were low. Findings highlight the possibility that exercise may be an effective intervention for symptom management in patients with irritable bowel syndrome; this may be particularly the case for constipation predominant patients.

PMID 18461499
Yujin Zhu, Xia Zheng, Yanqun Cong, Hua Chu, Michael Fried, Ning Dai, Mark Fox
Bloating and distention in irritable bowel syndrome: the role of gas production and visceral sensation after lactose ingestion in a population with lactase deficiency.
Am J Gastroenterol. 2013 Sep;108(9):1516-25. doi: 10.1038/ajg.2013.198. Epub 2013 Aug 6.
Abstract/Text OBJECTIVES: Bloating and distention are often attributed to dietary factors by patients with irritable bowel syndrome (IBS). This study examined the effects of gas production and visceral hypersensitivity on digestive symptoms after lactose ingestion in a population with lactase deficiency.
METHODS: IBS patients (n=277) and healthy controls (HCs, n=64) underwent a 20-g lactose hydrogen breath test (LHBT) with evaluation of hydrogen gas production and lactose intolerance (LI) symptoms. Abdominal distention (199 IBS, 40 HCs) was measured during LHBT. Rectal sensitivity (74 IBS, 64 HCs) was assessed by barostat studies.
RESULTS: Hydrogen production and distention were similar in IBS patients and HCs during LHBT; however, LI was more frequent in IBS (53.8 vs. 28.1%, P<0.001), especially bloating (39.0% vs. 14.1%, P<0.001) and borborygmi (39.0 vs. 21.9%, P=0.010). Only 59.0% of patients with bloating had distention. No correlation was observed between girth increment and bloating (P=0.585). IBS patients had lower rectal sensory thresholds (P=0.001). Multivariate analysis indicated that hydrogen production increased bloating (odds ratio (OR) 2.19, 95% confidence interval (CI) 1.09-4.39, P=0.028) and borborygmi (OR 12.37, 95% CI 3.34-45.83, P<0.001) but not distention (P=0.673). Visceral hypersensitivity was associated with bloating (OR 6.61, 95% CI 1.75-25.00, P=0.005) and total symptom score (OR 3.78, 95% CI 1.30-10.99, P=0.014).
CONCLUSIONS: Gas production and visceral hypersensitivity both contribute to digestive symptoms, especially bloating and borborygmi, in IBS patients after lactose ingestion. Objective abdominal distention is not correlated with subjective bloating.

PMID 23917444
Susan J Shepherd, Francis C Parker, Jane G Muir, Peter R Gibson
Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence.
Clin Gastroenterol Hepatol. 2008 Jul;6(7):765-71. doi: 10.1016/j.cgh.2008.02.058. Epub 2008 May 5.
Abstract/Text BACKGROUND & AIMS: Observational studies suggest dietary fructose restriction might lead to sustained symptomatic response in patients with irritable bowel syndrome (IBS) and fructose malabsorption. The aims of this study were first to determine whether the efficacy of this dietary change is due to dietary fructose restriction and second to define whether symptom relief was specific to free fructose or to poorly absorbed short-chain carbohydrates in general.
METHODS: The double-blinded, randomized, quadruple arm, placebo-controlled rechallenge trial took place in the general community. The 25 patients who had responded to dietary change were provided all food, low in free fructose and fructans, for the duration of the study. Patients were randomly challenged by graded dose introduction of fructose, fructans, alone or in combination, or glucose taken as drinks with meals for maximum test period of 2 weeks, with at least 10-day washout period between. For the main outcome measures, symptoms were monitored by daily diary entries and responses to a global symptom question.
RESULTS: Seventy percent of patients receiving fructose, 77% receiving fructans, and 79% receiving a mixture reported symptoms were not adequately controlled, compared with 14% receiving glucose (P < or = 0.002, McNemar test). Similarly, the severity of overall and individual symptoms was significantly and markedly less for glucose than other substances. Symptoms were induced in a dose-dependent manner and mimicked previous IBS symptoms.
CONCLUSIONS: In patients with IBS and fructose malabsorption, dietary restriction of fructose and/or fructans is likely to be responsible for symptomatic improvement, suggesting efficacy is due to restriction of poorly absorbed short-chain carbohydrates in general.

PMID 18456565
Derrick K Ong, Shaylyn B Mitchell, Jacqueline S Barrett, Sue J Shepherd, Peter M Irving, Jessica R Biesiekierski, Stuart Smith, Peter R Gibson, Jane G Muir
Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome.
J Gastroenterol Hepatol. 2010 Aug;25(8):1366-73. doi: 10.1111/j.1440-1746.2010.06370.x.
Abstract/Text BACKGROUND AND AIM: Reduction of short-chain poorly absorbed carbohydrates (FODMAPs) in the diet reduces symptoms of irritable bowel syndrome (IBS). In the present study, we aimed to compare the patterns of breath hydrogen and methane and symptoms produced in response to diets that differed only in FODMAP content.
METHODS: Fifteen healthy subjects and 15 with IBS (Rome III criteria) undertook a single-blind, crossover intervention trial involving consuming provided diets that were either low (9 g/day) or high (50 g/day) in FODMAPs for 2 days. Food and gastrointestinal symptom diaries were kept and breath samples collected hourly over 14 h on day 2 of each diet.
RESULTS: Higher levels of breath hydrogen were produced over the entire day with the high FODMAP diet for healthy volunteers (181 +/- 77 ppm.14 h vs 43 +/- 18; mean +/- SD P < 0.0001) and patients with IBS (242 +/- 79 vs 62 +/- 23; P < 0.0001), who had higher levels during each dietary period than the controls (P < 0.05). Breath methane, produced by 10 subjects within each group, was reduced with the high FODMAP intake in healthy subjects (47 +/- 29 vs 109 +/- 77; P = 0.043), but was not different in patients with IBS (126 +/- 153 vs 86 +/- 72). Gastrointestinal symptoms and lethargy were significantly induced by the high FODMAP diet in patients with IBS, while only increased flatus production was reported by healthy volunteers.
CONCLUSIONS: Dietary FODMAPs induce prolonged hydrogen production in the intestine that is greater in IBS, influence the amount of methane produced, and induce gastrointestinal and systemic symptoms experienced by patients with IBS. The results offer mechanisms underlying the efficacy of the low FODMAP diet in IBS.

PMID 20659225
Gregory L Austin, Christine B Dalton, Yuming Hu, Carolyn B Morris, Jane Hankins, Stephan R Weinland, Eric C Westman, William S Yancy, Douglas A Drossman
A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome.
Clin Gastroenterol Hepatol. 2009 Jun;7(6):706-708.e1. doi: 10.1016/j.cgh.2009.02.023. Epub 2009 Mar 10.
Abstract/Text BACKGROUND & AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This study prospectively evaluated a VLCD in IBS-D.
METHODS: Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 g carbohydrates/d). A responder was defined as having adequate relief of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life also were measured.
RESULTS: Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting adequate relief for all 4 VLCD weeks. Stool frequency decreased (2.6 +/- 0.8/d to 1.4 +/- 0.6/d; P < .001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score, 5.3 +/- 0.7 to 3.8 +/- 1.2; P < .001). Pain scores and quality-of-life measures significantly improved. Outcomes were independent of weight loss.
CONCLUSIONS: A VLCD provides adequate relief, and improves abdominal pain, stool habits, and quality of life in IBS-D.

PMID 19281859
S S C Rao, S Yu, A Fedewa
Systematic review: dietary fibre and FODMAP-restricted diet in the management of constipation and irritable bowel syndrome.
Aliment Pharmacol Ther. 2015 Jun;41(12):1256-70. doi: 10.1111/apt.13167. Epub 2015 Apr 22.
Abstract/Text BACKGROUND: Dietary fibre supplements have been advocated for the management of chronic constipation (CC) and irritable bowel syndrome (IBS). Recently, a fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) restricted diet has been recommended for IBS.
AIM: To systematically examine recent evidence for dietary interventions with fibre in CC and IBS and FODMAP-restricted diet in IBS, and provide recommendations.
METHODS: We searched PUBMED, MEDLINE, OVID and COCHRANE databases from 2004 to 2014. Published studies in adults with CC and IBS and constipation-predominant IBS (IBS-C) that compared fibre with placebo/alternative and FODMAP-restricted diet with alternative were included.
RESULTS: Of 550 potentially eligible clinical trials on fibre, 11 studies were found and of 23 potentially eligible studies on FODMAPs, six were found. A meta-analysis was not performed due to heterogeneity and methodological quality. Fibre was beneficial in 5/7 studies in CC and 3/3 studies in IBS-C. FODMAP-restricted diet improved overall IBS symptoms in 4/4 and IBS-C symptoms in 1/3 studies and three studies did not meet inclusion criteria. There were significant disparities in subject selection, interventions and outcome assessments in both fibre and FODMAPs studies.
CONCLUSIONS: Fibre supplementation is beneficial in mild to moderate CC and IBS-C, although larger, more rigorous and long-term RCTs are needed (Fair evidence-Level II, Grade B). Although the FODMAP-restricted diet may be effective in short-term management of selected patients with IBS (Fair evidence-Level II, Grade C) and IBS-C (Poor evidence-Level III, Grade C), more rigorous trials are needed to establish long-term efficacy and safety, particularly on colonic health and microbiome.

© 2015 John Wiley & Sons Ltd.
PMID 25903636
Emma P Halmos, Victoria A Power, Susan J Shepherd, Peter R Gibson, Jane G Muir
A diet low in FODMAPs reduces symptoms of irritable bowel syndrome.
Gastroenterology. 2014 Jan;146(1):67-75.e5. doi: 10.1053/j.gastro.2013.09.046. Epub 2013 Sep 25.
Abstract/Text BACKGROUND & AIMS: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) often is used to manage functional gastrointestinal symptoms in patients with irritable bowel syndrome (IBS), yet there is limited evidence of its efficacy, compared with a normal Western diet. We investigated the effects of a diet low in FODMAPs compared with an Australian diet, in a randomized, controlled, single-blind, cross-over trial of patients with IBS.
METHODS: In a study of 30 patients with IBS and 8 healthy individuals (controls, matched for demographics and diet), we collected dietary data from subjects for 1 habitual week. Participants then randomly were assigned to groups that received 21 days of either a diet low in FODMAPs or a typical Australian diet, followed by a washout period of at least 21 days, before crossing over to the alternate diet. Daily symptoms were rated using a 0- to 100-mm visual analogue scale. Almost all food was provided during the interventional diet periods, with a goal of less than 0.5 g intake of FODMAPs per meal for the low-FODMAP diet. All stools were collected from days 17-21 and assessed for frequency, weight, water content, and King's Stool Chart rating.
RESULTS: Subjects with IBS had lower overall gastrointestinal symptom scores (22.8; 95% confidence interval, 16.7-28.8 mm) while on a diet low in FODMAPs, compared with the Australian diet (44.9; 95% confidence interval, 36.6-53.1 mm; P < .001) and the subjects' habitual diet. Bloating, pain, and passage of wind also were reduced while IBS patients were on the low-FODMAP diet. Symptoms were minimal and unaltered by either diet among controls. Patients of all IBS subtypes had greater satisfaction with stool consistency while on the low-FODMAP diet, but diarrhea-predominant IBS was the only subtype with altered fecal frequency and King's Stool Chart scores.
CONCLUSIONS: In a controlled, cross-over study of patients with IBS, a diet low in FODMAPs effectively reduced functional gastrointestinal symptoms. This high-quality evidence supports its use as a first-line therapy.
CLINICAL TRIAL NUMBER: ACTRN12612001185853.

Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 24076059
Lisa Ruepert, A Otto Quartero, Niek J de Wit, Geert J van der Heijden, Gregory Rubin, Jean Wm Muris
Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.
Cochrane Database Syst Rev. 2011 Aug 10;(8):CD003460. doi: 10.1002/14651858.CD003460.pub3. Epub 2011 Aug 10.
Abstract/Text BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control.
OBJECTIVES: The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.
SEARCH STRATEGY: Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review.
SELECTION CRITERIA: Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of  bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included.
MAIN RESULTS: A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of  global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review.
AUTHORS' CONCLUSIONS: There is no evidence that bulking agents are effective for treating IBS.  There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures.

PMID 21833945
Alexander C Ford, Nicholas J Talley
Irritable bowel syndrome.
BMJ. 2012 Sep 4;345:e5836. Epub 2012 Sep 4.
Abstract/Text
PMID 22951548
D A Drossman, W E Whitehead, M Camilleri
Irritable bowel syndrome: a technical review for practice guideline development.
Gastroenterology. 1997 Jun;112(6):2120-37.
Abstract/Text
PMID 9178709
H J Kim, M I Vazquez Roque, M Camilleri, D Stephens, D D Burton, K Baxter, G Thomforde, A R Zinsmeister
A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating.
Neurogastroenterol Motil. 2005 Oct;17(5):687-96. doi: 10.1111/j.1365-2982.2005.00695.x.
Abstract/Text AIM: To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome (IBS) and significant bloating.
METHODS: Forty-eight patients with Rome II IBS were randomized in a parallel group, double-blind design to placebo or VSL# 3 twice daily (31 patients received 4 weeks and 17 patients 8 weeks of treatment). Pre- and post-treatment colonic transit measurements were performed using scintigraphy with (111)In charcoal. Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment. Weekly satisfactory relief of abdominal bloating was assessed.
RESULTS: Treatment with VSL# 3 was associated with reduced flatulence over the entire treatment period (placebo 39.5 +/- 2.6 vs VSL# 3 29.7 +/- 2.6, P = 0.011); similarly, during the first 4 weeks of treatment, flatulence scores were reduced (placebo 40.1 +/- 2.5 vs VSL# 3 30.8 +/- 2.5, P = 0.014). Proportions of responders for satisfactory relief of bloating, stool-related symptoms, abdominal pain and bloating scores were not different. Colonic transit was retarded with VSL# 3 relative to placebo (colon geometric center 2.27 +/- 0.20 vs 2.83 +/- 0.19, P = 0.05 respectively).
CONCLUSION: VSL# 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating.

PMID 16185307
Liam O'Mahony, Jane McCarthy, Peter Kelly, George Hurley, Fangyi Luo, Kersang Chen, Gerald C O'Sullivan, Barry Kiely, J Kevin Collins, Fergus Shanahan, Eamonn M M Quigley
Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.
Gastroenterology. 2005 Mar;128(3):541-51.
Abstract/Text BACKGROUND & AIMS: The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome (IBS) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain.
METHODS: Seventy-seven subjects with IBS were randomized to receive either Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624, each in a dose of 1 x 10 10 live bacterial cells in a malted milk drink, or the malted milk drink alone as placebo for 8 weeks. The cardinal symptoms of IBS were recorded on a daily basis and assessed each week. Quality of life assessment, stool microbiologic studies, and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase.
RESULTS: For all symptoms, with the exception of bowel movement frequency and consistency, those randomized to B infantis 35624 experienced a greater reduction in symptom scores; composite and individual scores for abdominal pain/discomfort, bloating/distention, and bowel movement difficulty were significantly lower than for placebo for those randomized to B infantis 35624 for most weeks of the treatment phase. At baseline, patients with IBS demonstrated an abnormal IL-10/IL-12 ratio, indicative of a proinflammatory, Th-1 state. This ratio was normalized by B infantis 35624 feeding alone.
CONCLUSIONS: B infantis 35624 alleviates symptoms in IBS; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine, suggesting an immune-modulating role for this organism, in this disorder.

PMID 15765388
S Nobaek, M L Johansson, G Molin, S Ahrné, B Jeppsson
Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome.
Am J Gastroenterol. 2000 May;95(5):1231-8. doi: 10.1111/j.1572-0241.2000.02015.x.
Abstract/Text OBJECTIVE: The influence of the gastrointestinal (GI) microflora in patients with irritable bowel syndrome (IBS) has not been clearly elucidated. This study was undertaken to see if patients with IBS have an imbalance in their normal colonic flora, as some bacterial taxa are more prone to gas production than others. We also wanted to study whether the flora could be altered by exogenous supplementation. In a previous study we have characterized the mucosa-associated lactobacilli in healthy individuals and found some strains with good colonizing ability. Upon colonization, they seemed to reduce gas formation.
METHODS: The study comprised 60 patients with IBS and a normal colonoscopy or barium enema. Patients fulfilling the Rome criteria, without a history of malabsorption, and with normal blood tests underwent a sigmoidoscopy with biopsy. They were randomized into two groups, one receiving 400 ml per day of a rose-hip drink containing 5 x 10(7) cfu/ml of Lactobacillus plantarum (DSM 9843) and 0.009 g/ml oat flour, and the other group receiving a plain rose-hip drink, comparable in color, texture, and taste. The administration lasted for 4 wk. The patients recorded their own GI function, starting 2 wk before the study and continuing throughout the study period. Twelve months after the end of the study all patients were asked to complete the same questionnaire regarding their symptomatology as at the start of the study.
RESULTS: All patients tolerated the products well. The patients receiving Lb. plantarum had these bacteria on rectal biopsies. There were no major changes of Enterobacteriaceae in either group, before or after the study, but the Enterococci increased in the placebo group and remained unchanged in the test group. Flatulence was rapidly and significantly reduced in the test group compared with the placebo group (number of days with abundant gas production, test group 6.5 before, 3.1 after vs 7.4 before and 5.6 after for the placebo group). Abdominal pain was reduced in both groups. At the 12-month follow-up, patients in the test group maintained a better overall GI function than control patients. There was no difference between the groups regarding bloating. Fifty-nine percent of the test group patients had a continuous intake of fermented products, whereas the corresponding figure for the control patients was 73%.
CONCLUSIONS: The results of the study indicate that the administration of Lb. plantarum with known probiotic properties decreased pain and flatulence in patients with IBS. The fiber content of the test solution was minimal and it is unlikely that the fiber content could have had any effect. This type of probiotic therapy warrants further studies in IBS patients.

PMID 10811333
E A Williams, J Stimpson, D Wang, S Plummer, I Garaiova, M E Barker, B M Corfe
Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study.
Aliment Pharmacol Ther. 2009 Jan;29(1):97-103. doi: 10.1111/j.1365-2036.2008.03848.x. Epub 2008 Sep 9.
Abstract/Text BACKGROUND: The efficacy of probiotics in alleviating the symptoms of irritable bowel syndrome (IBS) appears to be both strain- and dose-related.
AIM: To investigate the effect of LAB4, a multistrain probiotic preparation on symptoms of IBS. This probiotic preparation has not previously been assessed in IBS.
METHODS: Fifty-two participants with IBS, as defined by the Rome II criteria, participated in this double blind, randomized, placebo-controlled study. Participants were randomized to receive either a probiotic preparation comprising two strains of Lactobacillus acidophilus CUL60 (NCIMB 30157) and CUL21 (NCIMB 30156), Bifidobacterium lactis CUL34 (NCIMB 30172) and Bifidobacterium bifidum CUL20 (NCIMB 30153) at a total of 2.5 × 10(10) cfu/capsule or a placebo for 8 weeks. Participants reported their IBS symptoms using a questionnaire fortnightly during the intervention and at 2 weeks post-intervention.
RESULTS: A significantly greater improvement in the Symptom Severity Score of IBS and in scores for quality of life, days with pain and satisfaction with bowel habit was observed over the 8-week intervention period in the volunteers receiving the probiotic preparation than in the placebo group.
CONCLUSION: LAB4 multistrain probiotic supplement may benefit subjects with IBS.

© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
PMID 18785988
P Enck, K Zimmermann, G Menke, S Müller-Lissner, U Martens, S Klosterhalfen
A mixture of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) for treatment of the irritable bowel syndrome--a randomized controlled trial with primary care physicians.
Neurogastroenterol Motil. 2008 Oct;20(10):1103-9. doi: 10.1111/j.1365-2982.2008.01156.x. Epub 2008 Jun 28.
Abstract/Text Therapy trials with bacterial compounds in irritable bowel syndrome (IBS) have produced conflicting results. This study was performed in 1988 and 1989, and was re-analysed according to current IBS standards. Two hundred ninety-seven patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound ProSymbioflor((R)) (Symbiopharm GmbH, Herborn, Germany), an autolysate of cells and cell fragments of Enterococcus faecalis and Escherichia coli, or placebo in a double-blinded, randomized fashion. Patients were seen weekly by the physician, who assessed the presence of core IBS symptoms. Responders had at least a 50% decrease in global symptom score (GSS) and in abdominal pain score (APS) reports at >/=1 visit during treatment. The responder rate in GSS to the drug was 102/149 (68.5%) in comparison to placebo with 56/148 (37.8%) (P < 0.001), the improvement in APS was 108/149 (72.5%) and 66/148 (44.6%) respectively (P = 0.001). The number-needed-to-treat was 3.27 for GSS and 3.59 for the APS report. Kaplan-Meier analysis revealed a mean response time of 4-5 weeks for active treatment and more than 8 weeks for placebo (P < 0.0001). Treatment of IBS with the bacterial lysate ProSymbioflor is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners.

PMID 18565142
Michael Camilleri, Lin Chang
Challenges to the therapeutic pipeline for irritable bowel syndrome: end points and regulatory hurdles.
Gastroenterology. 2008 Dec;135(6):1877-91. doi: 10.1053/j.gastro.2008.09.005. Epub 2008 Oct 9.
Abstract/Text Recent advances in our understanding of basic neuroenteric mechanisms and the role of effectors and transmitters in the brain-gut axis have provided opportunities to develop new therapeutic agents for irritable bowel syndrome (IBS). Furthermore, human pharmacodynamic studies utilizing transit, colonic, or rectal sensitivity and brain imaging have been useful in determining therapeutic efficacy (particularly for drugs that act on motor function). This review provides an overview of medications that have not yet been approved for treatment of patients with IBS yet have shown promise in phase IIB trials. These include drugs that act on the serotonin receptor and transporter system: antidepressants, norepinephrine reuptake inhibitors, opioids, cholecystokinin antagonists, neurokinin-antagonists, chloride channel activators, guanylate cyclase C agonists, atypical benzodiazepines, probiotics, and antibiotics. The changing landscape in the regulatory approval process has impacted the development of IBS drugs. Guidance documents from regulatory agencies in Europe and the United States have focused on patients' reported outcomes and associated quality of life. After a decade of experience with different end points that have generated some data on psychometric validation and unprecedented information about responsiveness of the binary or global end points to drug therapy, it is necessary to pursue further validation studies before or during pivotal phase IIB or III trials. The hope of providing relief to patients should galvanize all parties to achieve these goals.

PMID 18848833
Darren M Brenner, Matthew J Moeller, William D Chey, Philip S Schoenfeld
The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review.
Am J Gastroenterol. 2009 Apr;104(4):1033-49; quiz 1050. doi: 10.1038/ajg.2009.25. Epub 2009 Mar 10.
Abstract/Text OBJECTIVES: Irritable bowel syndrome (IBS) is a common disorder and available therapies have limited efficacy. Mucosal inflammation and alterations in gut microflora may contribute to the development of IBS symptoms, and researchers have hypothesized that probiotics might improve these symptoms. The aim of this study was to perform a systematic review of randomized controlled trials (RCTs) evaluating the efficacy, safety, and tolerability of probiotics in the treatment of IBS.
METHODS: Comprehensive literature searches of multiple databases were performed. Study selection criteria were as follows: (i) RCTs, (ii) adults with IBS defined by Manning or Rome II criteria, (iii) single or combination probiotic vs. placebo, and (iv) improvement in IBS symptoms and/or decrease in frequency of adverse events reported. Data about study design and results were extracted in duplicate using standardized data extraction forms. Owing to variability in outcome measures, quantitative pooling of data was not feasible.
RESULTS: A total of 16 RCTs met selection criteria. Of those, 11 studies showed suboptimal study design with inadequate blinding, inadequate trial length, inadequate sample size, and/or lack of intention-to-treat analysis. None of the studies provided quantifiable data about both tolerability and adverse events. Bifidobacterium infantis 35624 showed significant improvement in the composite score for abdominal pain/discomfort, bloating/distention, and/or bowel movement difficulty compared with placebo (P<0.05) in two appropriately designed studies. No other probiotic showed significant improvement in IBS symptoms in an appropriately designed study.
CONCLUSIONS: B. infantis 35624 has shown efficacy for improvement of IBS symptoms. Most RCTs about the utility of probiotics in IBS have not used an appropriate study design and do not adequately report adverse events. Therefore, there is inadequate data to comment on the efficacy of other probiotics. Future probiotic studies should follow Rome II recommendations for appropriate design of an RCT.

PMID 19277023
P Moayyedi, A C Ford, N J Talley, F Cremonini, A E Foxx-Orenstein, L J Brandt, E M M Quigley
The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review.
Gut. 2010 Mar;59(3):325-32. doi: 10.1136/gut.2008.167270. Epub 2008 Dec 17.
Abstract/Text INTRODUCTION: Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted.
METHODS: MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models.
RESULTS: 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (chi(2)=28.3, p=0.001, I(2)=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=-0.34; 95% CI -0.60 to -0.07). There was statistically significant heterogeneity (chi(2)=67.04, p<0.001, I(2)=79%), but this was explained by one outlying trial.
CONCLUSION: Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

PMID 19091823
Nourieh Hoveyda, Carl Heneghan, Kamal R Mahtani, Rafael Perera, Nia Roberts, Paul Glasziou
A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome.
BMC Gastroenterol. 2009 Feb 16;9:15. doi: 10.1186/1471-230X-9-15. Epub 2009 Feb 16.
Abstract/Text BACKGROUND: Irritable Bowel Syndrome (IBS) is a common chronic gastrointestinal disorder and the evidence for efficacy of most drug therapies in the treatment of IBS is weak. A popular alternative is probiotics, which have been used in several conditions. including IBS. Probiotics are live microbial food supplements.The aim of this systematic review and meta-analysis of randomized trials study was to evaluate the efficacy of probiotics in alleviating symptoms in patients with irritable bowel syndrome. We searched Ovid versions of MEDLINE (1950-2007), EMBASE (1980-2007), CINAHL (1982-2007), AMED (1985-2007), the Cochrane library and hand searched retrieved papers.
RESULTS: We identified 14 randomized placebo controlled trials. Combined data suggested a modest improvement in overall symptoms after several weeks of treatment: for dichotomous data from seven trials the overall Odds Ratio (OR) was 1.6 (95% CI, 1.2 to 2.2); for continuous data from six trials the standardised mean difference (SMD) was 0.23 (95% CI, 0.07 to 0.38).For individual symptoms the results differed between the pooled dichotomous and pooled continuous data. Trials varied in relation to the length of treatment (4-26 weeks), dose, organisms and strengths of probiotics used.
CONCLUSION: Probiotics may have a role in alleviating some of the symptoms of IBS, a condition for which currently evidence of efficacy of drug therapies is weak. However, as IBS is a condition that is chronic and usually intermittent longer term trials are recommended. Such research should focus on the type, optimal dose of probiotics and the subgroups of patients who are likely to benefit the most.

PMID 19220890
R Spiller
Review article: probiotics and prebiotics in irritable bowel syndrome.
Aliment Pharmacol Ther. 2008 Aug 15;28(4):385-96. doi: 10.1111/j.1365-2036.2008.03750.x. Epub 2008 Jun 4.
Abstract/Text BACKGROUND: The human gut harbours a complex community of bacteria whose relationship with their host is normally mutually beneficial. Recent studies suggest a disturbance of this relationship in irritable bowel syndrome (IBS) and the potential to correct this using prebiotics and probiotics.
AIM: To review the mechanisms of action of probiotics and prebiotics in IBS and to assess their performance in clinical trials.
METHODS: Articles relating to modes of action and randomized control trials of treatment were reviewed by searching PubMed using terms 'probiotic', 'prebiotic' and 'irritable bowel'. Small uncontrolled studies in IBS were excluded.
RESULTS: Probiotics can enhance gut barrier function, inhibit pathogen binding and modulate gut inflammatory response. They can also reduce visceral hypersensitivity associated with both inflammation and psychological stress. Probiotics can alter colonic fermentation and stabilize the colonic microbiota. Several large randomized, placebo-controlled trials of adequate design have shown an improvement in flatulence and abdominal distension with a reduction in composite IBS symptoms scores.
CONCLUSIONS: Each probiotic has unique features and IBS patients are heterogeneous. Future efforts should be directed to identifying biomarkers of responsiveness to facilitate better targeting of treatment and hence improved efficacy.

PMID 18532993
Xing-lu Zhou, Wen Xu, Xiao-xiao Tang, Lai-sheng Luo, Jiang-feng Tu, Chen-jing Zhang, Xiang Xu, Qin-dong Wu, Wen-sheng Pan
Fecal lactoferrin in discriminating inflammatory bowel disease from irritable bowel syndrome: a diagnostic meta-analysis.
BMC Gastroenterol. 2014 Jul 7;14:121. doi: 10.1186/1471-230X-14-121. Epub 2014 Jul 7.
Abstract/Text BACKGROUND: To perform a meta-analysis evaluating the diagnostic ability of fecal lactoferrin (FL) to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS).
METHODS: The Medline, EMBASE, Web of Science, Cochrane library and CNKI databases were systematically searched for studies that used FL concentrations to distinguish between IBD and IBS. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model.
RESULTS: Seven studies, involving 1012 patients, were eligible for inclusion. In distinguishing IBD from IBS, FL had a pooled sensitivity of 0.78 (95% confidence interval [CI]: 0.75, 0.82), a specificity of 0.94 (95% CI: 0.91, 0.96), a positive likelihood ratio of 12.31 (95% CI: 5.93, 29.15), and a negative likelihood ratio of 0.23 (95% CI: 0.18, 0.29). The area under the summary receiver-operating characteristic curve was 0.94 (95% CI: 0.90, 0.98) and the diagnostic odds ratio was 52.65 (95% CI: 25.69, 107.91).
CONCLUSIONS: FL, as a noninvasive and simple marker, is useful in differentiating between IBD and IBS.

PMID 25002150
P P Toskes, K L Connery, T W Ritchey
Calcium polycarbophil compared with placebo in irritable bowel syndrome.
Aliment Pharmacol Ther. 1993 Feb;7(1):87-92.
Abstract/Text Calcium polycarbophil was compared with placebo in 23 patients with irritable bowel syndrome in a six-month, randomized double-blind crossover study. Patients received polycarbophil tablets at a dosage of 6 g/day (twelve 0.5-g tablets) or matching placebo tablets. At study end, among patients expressing a preference, 15 of 21 (71%) chose polycarbophil over placebo for relief of the symptoms of irritable bowel syndrome. Statistically significant differences favouring polycarbophil were found among the following patient subgroups: 15 (79%) of 19 with constipation: all six with alternating diarrhoea and constipation; 13 (87%) of 15 with bloating: and 11 (92%) of 12 with two or more symptoms. Polycarbophil was rated better than placebo in monthly global responses to therapy. Patient diary entries showed statistically significant improvement for ease of passage with polycarbophil. Polycarbophil was rated better than placebo for relief of nausea, pain, and bloating. The data suggest that calcium polycarbophil can benefit irritable bowel syndrome patients with constipation or alternating diarrhoea and constipation and may be particularly useful in patients with bloating as a major complaint.

PMID 8439642
J Tack, M Fried, L A Houghton, J Spicak, G Fisher
Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective.
Aliment Pharmacol Ther. 2006 Jul 15;24(2):183-205. doi: 10.1111/j.1365-2036.2006.02938.x.
Abstract/Text BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder, characterized by abdominal pain/discomfort, bloating and altered bowel habit.
AIM: To conduct a systematic evidence-based review of pharmacological therapies currently used, or in clinical development, for the treatment of IBS in Europe. The safety and tolerability of these therapies are the subject of an accompanying review.
METHODS: A literature search was completed for randomized controlled studies which included adult patients with IBS and an active or placebo control, assessed IBS symptoms, and were published in English between January 1980 and June 2005. The level of evidence for efficacy was graded according to the quality of the trial design and the study outcome.
RESULTS: There is some evidence for improvement of individual IBS symptoms with antidiarrhoeals (diarrhoea), antispasmodics (abdominal pain/discomfort), bulking agents (constipation), tricyclic antidepressants (abdominal pain/discomfort) and behavioural therapy. In contrast, there is strong evidence for the improvement of global IBS symptoms with two new serotonergic agents: the 5-HT4 selective agonist tegaserod (IBS with constipation) and the 5-HT3 antagonist alosetron (IBS with diarrhoea). Further data are required for the 5-HT3 antagonist, cilansetron, and the mixed 5-HT3 antagonist/5-HT4 agonist renzapride before their utility in IBS can be appraised.
CONCLUSIONS: There is limited evidence for the efficacy, safety and tolerability of therapies currently available in Europe for the treatment of IBS. Overall, there is an absence of pharmacological agents licensed specifically for the treatment of IBS subtypes, and new agents are awaited in Europe that will allow changes in clinical practice to focus on and improve global IBS symptoms.

PMID 16842448
R Heading, K Bardhan, S Hollerbach, A Lanas, G Fisher
Systematic review: the safety and tolerability of pharmacological agents for treatment of irritable bowel syndrome--a European perspective.
Aliment Pharmacol Ther. 2006 Jul 15;24(2):207-36. doi: 10.1111/j.1365-2036.2006.02937.x.
Abstract/Text AIM: To use an evidence-based approach to evaluate the safety and tolerability of the treatments available for irritable bowel syndrome (IBS), or in clinical development, in Europe. A separate review appraises the evidence for the efficacy of these therapies.
METHODS: A literature search (for 1980 to 2005) was completed for all relevant clinical trial data and other articles which included safety information on the use of pharmacological IBS therapies. Clinical trials were scored according to the level of safety information, and adverse event incidence reported when possible.
RESULTS: The tolerability of many of the agents used to treat IBS in Europe is poorly understood. However, serotonergic agents, such as tegaserod and alosetron, which are currently unavailable in Europe, have undergone rigorous assessment in IBS and their benefits have been established. Following initial marketing of alosetron for use in patients with IBS with diarrhoea, concerns about severe constipation and ischaemic colitis resulted in restriction of its use to women with severe IBS symptoms. This highlights the importance of post-marketing surveillance and post-marketing studies in refining the therapeutic indication of new IBS therapies, which will help to identify appropriate recipients for the drug and establish the impact of adverse reactions in clinical practice.
CONCLUSIONS: There is a significant lack of data on the safety and tolerability of the therapies currently used routinely to treat IBS in Europe. The newer agents have undergone rigorous assessment, such that their benefits and risks in treating IBS are established. Defining their place among the spectrum of available therapies remains challenging when the benefits and risks of the older treatments are so poorly characterized.

PMID 16842449
B Lavö, M Stenstam, A L Nielsen
Loperamide in treatment of irritable bowel syndrome--a double-blind placebo controlled study.
Scand J Gastroenterol Suppl. 1987;130:77-80.
Abstract/Text The effects of loperamide in patients with IBS (all had diarrhoea as a main symptom) were studied in a double-blind placebo controlled trial. Subjective overall response stool consistency and six individual symptoms (urgency, pain, frequency, flatulence, borborygmi and painful propulsions) were studied over a 13 week long treatment period. Twenty-one patients out of 25 completed the trial, 11 in the loperamide group and 10 in the placebo group. A significant advantage for loperamide was found for stool consistency (p less than 0.001), pain (p less than 0.02) and urgency (p less than 0.05). Subjective overall response was also significantly better in the loperamide group (p less than 0.03). Self-titration of dose and administration in a single nightly dose was safe and efficient.

PMID 3306903
N Hovdenak
Loperamide treatment of the irritable bowel syndrome.
Scand J Gastroenterol Suppl. 1987;130:81-4.
Abstract/Text The effect of loperamide was investigated in a double-blind, placebo-controlled study in 60 patients with irritable bowel syndrome (IBS). Active treatment was given in low dosage (4 mg nocte). The effect of treatment was assessed in clinical subgroups. In a group of patients with painless diarrhoea (n = 16) there was a highly significant improvement in stool frequency and consistency. In a group with alternating bowel habits and abdominal pain (n = 21) there was also a statistically significant improvement in stool frequency and consistency as well as significantly fewer painful days during loperamide treatment. Patients with alternating bowel habits and no pain (n = 12) experienced no symptomatic improvement, and patients with constipation (n = 9) generally felt worse on loperamide. No side effects were encountered. It is concluded that loperamide can be considered an alternative symptomatic treatment in some IBS patients whose main symptoms are painless diarrhoea or alternating bowel habits associated with abdominal pain.

PMID 3306904
P S Efskind, T Bernklev, M H Vatn
A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome.
Scand J Gastroenterol. 1996 May;31(5):463-8. doi: 10.3109/00365529609006766.
Abstract/Text BACKGROUND: Loperamide has a relaxing effect on localized and segmental large-bowel spasms. On the basis of previously observed effects on pain and stool habits in patients with diarrhoea, the present trial intended to examine the regulating effect in an unselected cohort of patients with the irritable bowel syndrome (IBS). The symptoms in IBS are dependent on variations in motility initiated by different mechanisms. Therefore, when examining the effect of treatment, characterization of the patient material is important.
METHODS: Ninety patients were included in this prospective double-blind trial comparing loperamide with placebo over 5 weeks. The two groups were characterized and compared with healthy controls (n = 33), matched by age and sex. Demographic, clinical, and biochemical data were recorded.
RESULTS: Clinical variables and social and personal relationships were similar for the loperamide group (n = 35), the placebo group ( n = 34), the dropouts (n = 21), and controls. Somatic diseases and mental disturbances were increased in the patients compared with the controls. Throughout the 5 weeks of treatment an improved stool consistency (32%), reduced defecation frequency (36%), and reduced intensity of pain (30%) were found in the loperamide group. An increase in nightly pain was observed in the loperamide group.
CONCLUSIONS: This trial lends support to a multifactorial aetiology in IBS. Treatment must be individualized with regard to both the effect and the risk of constipation and abdominal pain. The trial shows a benefit of loperamide in an unselected cohort of IBS patients with regard to stool frequency, stool consistency, and the overall pain intensity, but with increased abdominal pain during the night. It should be recommended that the patients take the medication in divided daily doses.

PMID 8734343
Shin Fukudo, Motoko Ida, Hiraku Akiho, Yoshihiro Nakashima, Kei Matsueda
Effect of ramosetron on stool consistency in male patients with irritable bowel syndrome with diarrhea.
Clin Gastroenterol Hepatol. 2014 Jun;12(6):953-9.e4. doi: 10.1016/j.cgh.2013.11.024. Epub 2013 Dec 4.
Abstract/Text BACKGROUND & AIMS: Ramosetron, a serotonin (5-hydroxytryptamine)-3 receptor antagonist with high selectivity, reduced stress-induced diarrhea and defecation caused by corticotropin-releasing hormone in rats. However, there have been no clinical trials of its effect in patients with diarrhea and irritable bowel syndrome (IBS-D). We performed a randomized, double-blind, placebo-controlled trial to determine whether ramosetron reduces diarrhea in these patients.
METHODS: Our study included 296 male outpatients with IBS-D treated at 52 centers in Japan. Patients were given 5 μg oral ramosetron (n = 147) or placebo (n = 149) once daily for 12 weeks after a 1-week baseline period. The primary end point was increased stool consistency in the first month. Secondary end points included relief of overall IBS symptoms and increased IBS-related quality of life.
RESULTS: More patients given ramosetron (74, 50.3%) than those given placebo (29, 19.6%) reported improved stool consistency in the first month (P < .001). The relative risk and number needed to treat were 2.57 (95% confidence interval, 1.79-3.70) and 3.25 (95% confidence interval, 2.44-4.89), respectively. The ramosetron group had significantly higher monthly rates of relief of overall IBS symptoms and IBS-related quality of life than the placebo group.
CONCLUSIONS: Ramosetron (5 μg oral, once daily for 12 weeks) improved stool consistency in male patients with IBS-D, compared with placebo. These study results, along with the pharmacologic profile of ramosetron, indicate that increased stool consistency is the best end point for studies of ramosetron in patients with IBS-D. Clinicaltrials.gov No, NCT01225237.

Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 24315882
Michele M Spence, Fatima A Karim, Eric A Lee, Rita L Hui, Nancy E Gibbs
Risk of Injury in Older Adults Using Gastrointestinal Antispasmodic and Anticholinergic Medications.
J Am Geriatr Soc. 2015 Jun;63(6):1197-202. doi: 10.1111/jgs.13434. Epub 2015 Jun 11.
Abstract/Text OBJECTIVES: To determine the risk of injury associated with gastrointestinal (GI) antispasmodic and anticholinergic use in elderly adults.
DESIGN: Retrospective case-control study.
SETTING: Integrated healthcare system.
PARTICIPANTS: Healthcare system members aged 65 and older (N = 260,010; 54,152 cases, 205,858 controls).
MEASUREMENTS: Cases were identified as individuals with an injury resulting in a hospitalization, emergency department, or urgent care visit (index date) from January 2009 through December 2010. Cases and controls were matched in a 1:4 ratio based on age and sex. GI antispasmodic and anticholinergic current and past exposure for cases and controls was evaluated. Individuals were classified as current users if the days' supply of the GI prescription overlapped the index date and past users if the days' supply ended more than 60 days before the index date. Duration of use for current users was analyzed for short- and long-term use. Conditional logistic regression produced adjusted odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS: Of the total population, 1,068 (0.4%) had current exposure to a GI antispasmodic or anticholinergic (302 (0.6%) cases, 766 (0.4%) controls). Current users had a small but significantly greater risk of injury than nonusers (OR = 1.16, 95% CI = 1.01-1.34, P = .03). Past use was not significantly different from no use. Short-term users had a significantly greater risk of injury (OR = 1.31, 95% CI = 1.01-1.70, P = .04) than nonusers. Long-term use was associated with greater risk, but the difference was not statistically significant.
CONCLUSION: Older adults using GI antispasmodic and anticholinergic drugs have greater risk of injury. These findings support recommendations to limit the prescribing of GI antispasmodics and anticholinergics in elderly adults.

© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
PMID 26096393
S A Müller-Lissner, I Fumagalli, K D Bardhan, F Pace, E Pecher, B Nault, P Rüegg
Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation.
Aliment Pharmacol Ther. 2001 Oct;15(10):1655-66.
Abstract/Text AIM: To investigate the efficacy and safety of tegaserod, a novel 5-HT(4) receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study.
METHODS: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks.
RESULTS: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo.
CONCLUSIONS: Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.

PMID 11564007
J Novick, P Miner, R Krause, K Glebas, H Bliesath, G Ligozio, P Rüegg, M Lefkowitz
A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation.
Aliment Pharmacol Ther. 2002 Nov;16(11):1877-88.
Abstract/Text BACKGROUND: Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females.
AIM: To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation.
METHODS: In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating.
RESULTS: Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients.
CONCLUSIONS: Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.

PMID 12390096
M Van Outryve, R Milo, J Toussaint, P Van Eeghem
"Prokinetic" treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride.
J Clin Gastroenterol. 1991 Feb;13(1):49-57.
Abstract/Text The effects of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome (IBS) were evaluated in a randomized, double-blind, placebo-controlled study. Sixty-nine IBS patients were assigned to a 12-week treatment with either 5 mg cisapride or placebo t.i.d.; this dosage could be changed if necessary. The mean weekly number of days on which a stool was passed in the cisapride and placebo group increased to 5.3 and 4.4 (p less than 0.05) during weeks 8-12 of treatment, and the number of days with stools of normal consistency increased to 3.5 and 1.9 (p less than 0.05), respectively. At week 12, the reduction in severity and frequency scores for abdominal pain was significantly greater (p less than or equal to 0.05) in the cisapride group (60 and 61%) than in the placebo group (40 and 32%), as it was for abdominal distension (p less than 0.05). Cisapride tended to be better than placebo in diminishing flatulence. In 71% versus 39% of the patients the overall rating for the response to treatment was good or excellent at week 12. Cisapride was well tolerated. These results suggest that the drug will be useful for the management of constipation-predominant IBS.

PMID 2007745
Dieter J Ziegenhagen, Wolfgang Kruis
Cisapride treatment of constipation-predominant irritable bowel syndrome is not superior to placebo.
J Gastroenterol Hepatol. 2004 Jul;19(7):744-9. doi: 10.1111/j.1440-1746.2004.03384.x.
Abstract/Text BACKGROUND AND AIM: Previous studies with cisapride reported conflicting results in patients with constipation-predominant irritable bowel syndrome (IBS). To gain further evidence, this randomized double-blind study was carried out.
METHODS: Eighty-two symptomatic outpatients were randomized to receive either 5 mg oral cisapride or placebo three times daily for a period of 12 weeks. In patients without satisfactory improvement after 4 weeks, the dose was doubled. Symptom evaluation used visual analog scales (VAS) and the investigators' global assessment.
RESULTS: After 4 weeks, in 18 (45%) cisapride and 24 (57%) placebo patients the dose was doubled because of insufficient improvement of symptoms. The mean VAS score for patients' global rating of IBS symptoms at baseline was 67.5 mm for cisapride versus 70.7 mm for placebo, and improved to 38.4 mm versus 44.5 mm after 12 weeks of treatment. Investigators rated the overall effect of therapy as good or excellent in 70% of the cisapride and 50% of the placebo group. Neither these nor further efficacy parameter differences reached statistical significance.
CONCLUSIONS: These results indicate that the effect of 15-30 mg cisapride daily on symptoms of constipation-predominant IBS is not significantly superior to placebo. During the 12 week treatment of this trial cisapride proved to be safe and tolerable.

PMID 15209619
A M George, N L Meyers, R I Hickling
Clinical trial: renzapride therapy for constipation-predominant irritable bowel syndrome--multicentre, randomized, placebo-controlled, double-blind study in primary healthcare setting.
Aliment Pharmacol Ther. 2008 May;27(9):830-7. doi: 10.1111/j.1365-2036.2008.03649.x. Epub 2008 Feb 14.
Abstract/Text BACKGROUND: Relatively few pharmacological treatment options are available for treating patients with irritable bowel syndrome. New and effective medicines are urgently required.
AIM: To identify an appropriate dosage of renzapride (a 5-HT(4) receptor full agonist/5-HT(3) receptor antagonist) to treat abdominal pain/discomfort in patients with constipation-predominant irritable bowel syndrome.
METHODS: In this randomized, placebo-controlled, phase IIb study in the primary care setting, men and women were randomized to placebo or renzapride (1, 2 or 4 mg/day) for 12 weeks. The primary outcome measure was patient self-assessed relief of abdominal pain/discomfort during weeks 5-12. Secondary efficacy measures included patients' assessment of their bowel habits, stool consistency and quality of life.
RESULTS: Although there were no statistically significant differences between renzapride and placebo for relief from abdominal pain/discomfort, responder rates in the renzapride treatment groups increased dose dependently, with the 4 mg/day group being consistently numerically greater than placebo. Importantly, a larger numerical treatment difference vs. placebo was observed in women (8% and 12% respectively). Statistically significant improvements in bowel movement frequency and stool consistency were observed in the 4 mg/day group relative to placebo. Renzapride was well tolerated at all doses.
CONCLUSIONS: This study confirms the gastrointestinal prokinetic effects of renzparide. The data also suggested a potentially beneficial effect on abdominal pain/discomfort in women with constipation-predominant irritable bowel syndrome.

PMID 18284648
J F Johanson, D A Drossman, R Panas, A Wahle, R Ueno
Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation.
Aliment Pharmacol Ther. 2008 Apr;27(8):685-96. doi: 10.1111/j.1365-2036.2008.03629.x. Epub 2008 Jan 28.
Abstract/Text BACKGROUND: Analyses of a trial in constipated patients indicated that lubiprostone may be an effective treatment for irritable bowel syndrome with constipation.
AIM: To assess the efficacy and safety of three lubiprostone doses for irritable bowel syndrome with constipation.
METHODS: 195 irritable bowel syndrome with constipation patients received daily doses of 16 [8 microg twice daily (b.d.)], 32 (16 microg b.d.) or 48 microg (24 microg b.d.) lubiprostone or placebo b.d. for 3 months. Gastrointestinal parameters were recorded in diaries daily by patients.
RESULTS: After 1 month, lubiprostone showed significantly greater improvements in mean abdominal discomfort/pain scores vs. placebo (P = 0.023). After 2 months, all lubiprostone groups showed significantly greater improvements in mean abdominal discomfort/pain scores (P < or = 0.039). After 3 months of treatment, the improvement in each lubiprostone arm was greater than placebo, but the test for trend was no longer significant. Treatment with lubiprostone showed significantly higher rates of gastrointestinal adverse events (P = 0.020), especially diarrhoea and nausea.
CONCLUSION: Lubiprostone significantly improved gastrointestinal symptoms of irritable bowel syndrome with constipation at all doses. Higher doses of lubiprostone, especially the 48 microg/day group, were associated with more gastrointestinal adverse events. From these data, the 16 microg/day dose demonstrated the optimal combination of efficacy and safety. These results warrant further study of lubiprostone for treatment of irritable bowel syndrome with constipation patients.

PMID 18248656
D A Drossman, W D Chey, J F Johanson, R Fass, C Scott, R Panas, R Ueno
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):329-41. doi: 10.1111/j.1365-2036.2008.03881.x. Epub 2008 Nov 4.
Abstract/Text BACKGROUND: Effective treatments for irritable bowel syndrome with constipation (IBS-C) are lacking.
AIM: To assess the efficacy and safety of lubiprostone in IBS-C.
METHODS: A combined analysis was performed among 1171 patients with a Rome II diagnosis of IBS-C in two phase-3 randomized trials of lubiprostone 8 mcg vs. placebo twice daily for 12 weeks. Using a balanced seven-point Likert scale ranging from significantly relieved (+3), to significantly worse (-3), patients responded on their electronic diary to the question: 'How would you rate your relief of IBS symptoms over the past week compared to how you felt before you entered the study?'. The primary efficacy endpoint was the percentage of overall responders.
RESULTS: Using an intent-to-treat analysis with last observation carried forward, a significantly higher percentage of lubiprostone-treated patients were considered overall responders compared with those treated with placebo (17.9% vs. 10.1%, P=0.001). Patients treated with lubiprostone reported a similar incidence of adverse events to those treated with placebo.
CONCLUSIONS: The percentage of overall responders based on patient-rated assessments of IBS-C symptoms was significantly improved in patients treated with lubiprostone 8 mcg twice daily compared to those treated with placebo. Lubiprostone was well tolerated with a favourable safety profile.

PMID 19006537
S Fukudo, M Hongo, H Kaneko, R Ueno
Efficacy and safety of oral lubiprostone in constipated patients with or without irritable bowel syndrome: a randomized, placebo-controlled and dose-finding study.
Neurogastroenterol Motil. 2011 Jun;23(6):544-e205. doi: 10.1111/j.1365-2982.2011.01668.x. Epub 2011 Feb 9.
Abstract/Text BACKGROUND: Lubiprostone is a prostone analog with a novel mechanism of action involving type-2 chloride channel activation. The aim of this work was to perform a dose-finding study for lubiprostone for the treatment of constipation with or without irritable bowel syndrome (IBS) in Japan.
METHODS: A total of 170 patients (128 without IBS and 42 with IBS) with chronic idiopathic constipation (CIC) randomly received a placebo (n=42) or 16μg (n=41), 32μg (n=43), or 48μg (n=44) of lubiprostone daily for 2weeks.
KEY RESULTS: There was a statistically significant and dose-dependent increase in change from baseline in the weekly average number of spontaneous bowel movements at week 1 (placebo: 1.5±0.4; 16μg: 2.3±0.4, 32μg: 3.5±0.5; and 48μg: 6.8±1.1, per week, mean±SE; P<0.0001). These primary endpoint results were significant on stratified analysis when patients were limited to those without IBS (P<0.0001). The primary endpoint in patients with IBS treated with 48μg of lubiprostone was significantly better than those given placebo (P=0.0086). Dose dependency was also seen for the secondary efficacy endpoints. Lubiprostone produced no serious side effects.
CONCLUSIONS & INFERENCES: Our results suggest that lubiprostone produced a steady and effective improvement in the symptoms of CIC with or without IBS in a dose-dependent manner with a good safety profile and tolerability in a Japanese population.

© 2011 Blackwell Publishing Ltd.
PMID 21303430
Jeffrey Medoff, Seymour Katz, Pramod Malik, Daniel Pambianco, Ronald Pruitt, John Poulos, Jeffrey Rank, Martin Rose
Open-label, dose-ranging pilot study of 4 weeks of low-dose therapy with sodium phosphate tablets in chronically constipated adults.
Clin Ther. 2004 Sep;26(9):1479-91. doi: 10.1016/j.clinthera.2004.09.007.
Abstract/Text BACKGROUND: The tablet formulation of sodium phosphate (NaP) is a prescription osmotic purgative that has been marketed since 2001. The use of NaP tablets in patients with constipation has not been studied previously.
OBJECTIVE: This study assessed the tolerability and efficacy of 28 days of therapy with NaP tablets (1.5 g NaP/tablet) in patients with chronic constipation.
METHODS: Adults with functional constipation or constipation-predominant irritable bowel syndrome and Z-3 spontaneous bowel movements (BMs) during the 7-day screening/baseline period were eligible for this open-label, dose-ranging study. Patients were randomized to receive starting doses of 4 NaP tablets (group A) or 8 NaP tablets (group B) each morning for 28 days. After a minimum of 48 hours, the NaP dose could be titrated upward (in the case of no BM or no relief of symptoms) or downward (in the case of a predefined excess laxative response) by 2 tablets/d to a minimum of 2 tablets/d or a maximum of 12 tablets/d. Patients kept a diary of their BMs and gastrointestinal symptoms. A serum chemistry panel was obtained weekly. The primary end points were the constipation response (based on the change from baseline in weekly number of BMs) and the global sense response (based on daily scores for the patient's overall sense of change in their bowel problems).
RESULTS: At randomization, there were 18 patients in group A and 25 in group B. Of these, 40 patients (16 group A, 24 group B) had > or 7 days of diary information while taking study treatment and were evaluable for efficacy. The constipation response rate was 100% in group A and 95.8% in group B, and the respective global sense response rates were 68.8% and 79.2%. Four patients in group B withdrew due to adverse events, none of which were serious. Five patients had occasional hypokalemia that required no treatment. Changes from baseline in serum concentrations of calcium, inorganic phosphorus, and potassium were not clinically significant and did not require treatment.
CONCLUSIONS: In this small study, NaP tablets taken daily were generally well tolerated (particularly in the low-dose group) and produced prompt relief of constipation--generally within the first week of treatment--that was sustained over the 28-day treatment period. A reasonable starting dose appears to be 2 to 4 tablets (3-6 g NaP) daily.

PMID 15531010
Abstract/Text (1) Patients frequently complain of occasional bowel movement disorders, associated with abdominal pain or discomfort, but they are rarely due to an underlying organ involvement. Even when patients have recurrent symptoms, serious disorders are no more frequent in these patients than in the general population, unless other manifestations, anaemia, or an inflammatory syndrome is also present; (2) There is currently no way of radically modifying the natural course of recurrent irritable bowel syndrome; (3) The effects of antispasmodics on abdominal pain have been tested in about 20 randomised controlled trials. Pinaverium and peppermint essential oil have the best-documented efficacy and only moderate adverse effects. Antispasmodics with marked atropinic effects do not have a favourable risk-benefit balance; (4) Tricylic antidepressants seem to have only modest analgesic effects in this setting. In contrast, their adverse effects are frequent and they have somewhat negative risk-benefit balances. Nor has the efficacy of selective serotonin reuptake inhibitor antidepressants (SSRIs) been demonstrated; (5) Alosetron and tegaserod carry a risk of potentially life-threatening adverse effects and therefore have negative risk-benefit balances; (6) Seeds of plants such as psyllium and ispaghul, as well as raw apples and pears, have a limited impact on constipation and pain. Osmotic laxatives are effective on constipation. Symptomatic treatments for constipation can sometimes aggravate abdominal discomfort; (7) Loperamide has been poorly assessed in patients with recurrent irritable bowel syndrome with diarrhoea. It modestly slows bowel movement but does not relieve pain or abdominal discomfort; (8) Dietary measures have not been tested in comparative trials. Some patients are convinced that certain foods provoke a recurrence of irritable bowel syndrome, but restrictive diets carry a risk of nutritional deficiencies; (9) Various techniques intended to control emotional and psychological disturbances have been proposed, including relaxation, biofeedback, hypnosis, and psychotherapy. The results of clinical trials are not convincing; (10) Oral products containing live bacteria, designed to change the equilibrium of intestinal flora, have been tested in 13 placebo-controlled trials, with inconsistent results. A few cases of septicaemia have been reported; (11) The six available trials of acupuncture (versus sham acupuncture) showed no more than a placebo effect; (12) In practice, patients who have recurrent irritable bowel syndrome but with no other signs of a condition warranting specific treatment should be reassured as to the harmless nature of their disorder if a careful physical examination and basic laboratory tests are negative. The only available treatments have purely symptomatic effects and only limited efficacy. It is best to avoid using all treatments and additional diagnostic investigations that carry a risk of disproportionate adverse effects.

PMID 19585728
V Khoshoo, C Armstead, L Landry
Effect of a laxative with and without tegaserod in adolescents with constipation predominant irritable bowel syndrome.
Aliment Pharmacol Ther. 2006 Jan 1;23(1):191-6. doi: 10.1111/j.1365-2036.2006.02705.x.
Abstract/Text AIM: To determine the effect of a laxative alone and in combination with tegaserod in alleviating pain and improving stool frequency in adolescents with constipation predominant irritable bowel syndrome.
PATIENTS: Forty-eight postpubertal adolescents of both sexes with constipation predominant irritable bowel syndrome, as defined by Rome II criteria, were randomly allocated to Group A (n = 27) for treatment with a laxative (polyethylene glycol 3350 oral solution) only or Group B (n = 21) for combination therapy with the laxative and tegaserod. Symptoms of abdominal pain (scale 0-10) and frequency of bowel movements were recorded daily in the pre-treatment phase and the post-treatment phase after a 7-day 'washout' period. Patients served as their own controls.
RESULTS: Treatment with the laxative alone (Group A) resulted in significant increase in frequency of bowel movements (P < 0.05), but not significant improvement in pain (P > 0.05). Treatment with the combination of the laxative and tegaserod (Group B) led to significant increase in the frequency of bowel movements and also significant reduction in pain (P < 0.05).
CONCLUSIONS: The laxative alone improved stooling but not pain in adolescents with constipation predominant irritable bowel syndrome. Addition of tegaserod resulted in alleviation of pain as well.

PMID 16393297
R Wulkow, J-M Vix, C Schuijt, H Peil, M A Kamm, C Jordan
Randomised, placebo-controlled, double-blind study to investigate the efficacy and safety of the acute use of sodium picosulphate in patients with chronic constipation.
Int J Clin Pract. 2007 Jun;61(6):944-50. doi: 10.1111/j.1742-1241.2007.01374.x.
Abstract/Text There are few studies supporting the effective and safe use of laxatives for constipation. This study examined the short-term efficacy and safety of sodium picosulphate in patients with chronic constipation. Patients with a history of chronic constipation for at least 3 months were randomised to receive 7 mg sodium picosulphate or placebo for three consecutive nights. Patients recorded stool frequency and consistency, straining, bloating, and pain at baseline and during treatment. Vital signs, haematocrit, serum creatinine and electrolytes were monitored. Primary end-point for efficacy was the occurrence of a response to treatment, defined as improvement in stool frequency and occurrence of straining. All 57 randomised patients (sodium picosulphate n = 29, placebo n = 28; mean age 54.8 and 54.1 years) completed the study. Sodium picosulphate produced a treatment response (improved stool frequency and straining) in 82.8% compared with 50% in the placebo group (p = 0.010) and reduced bloating more often than placebo. There were no serious adverse events and one patient with diarrhoea and another with abdominal pain in each treatment group. There were no cardiovascular effects, changes in serum haematocrit, creatinine or electrolytes in either group. This study confirmed that sodium picosulphate is an effective, well-tolerated and safe laxative in the acute treatment of constipation.

PMID 17504357
Stefan Mueller-Lissner, Michael A Kamm, Arnold Wald, Ulrika Hinkel, Ursula Koehler, Erika Richter, Jürgen Bubeck
Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation.
Am J Gastroenterol. 2010 Apr;105(4):897-903. doi: 10.1038/ajg.2010.41. Epub 2010 Feb 23.
Abstract/Text OBJECTIVES: Although it has been used as a laxative for many years, high-quality trials assessing the efficacy of the laxative sodium picosulfate (SPS) are lacking. The purpose of this study was to assess the efficacy and safety of 4-week treatment with SPS in patients with functional constipation as defined by the Rome III diagnostic criteria.
METHODS: This study was a randomized, double-blind, placebo-controlled, parallel-group study in 45 general practices in Germany. A total of 468 patients with chronic constipation presenting to their general practitioner and fulfilling the Rome III diagnostic criteria were screened. After a 2-week baseline period, 367 patients were randomized to either SPS drops or matching placebo in a 2:1 ratio for 4 weeks. Dose titration was permitted throughout treatment. Patients without a bowel movement for more than 72 h were allowed to use a "rescue" bisacodyl suppository. The primary end point was the mean number of complete spontaneous bowel movements (CSBMs) per week. A spontaneous bowel movement (SBM) was defined as a stool not induced by rescue medication, whereas a CSBM was defined as an SBM associated with a sensation of complete evacuation.
RESULTS: The mean number (+/-s.e.) of CSBMs per week increased from 0.9+/-0.1 to 3.4+/-0.2 in the SPS group and from 1.1+/-0.1 to 1.7+/-0.1 in the placebo group (P<0.0001). The percentage of patients reaching an increase of > or =1 in the mean number of CSBMs per week compared to baseline was 65.5% vs. 32.3%, respectively (P<0.0001). The percentage of patients reaching a mean number of at least three CSBMs per week was 51.1% in the SPS group and 18.0% in the placebo group (P<0.0001). After 24 h, approximately 69% of patients in the SPS group and 53% in the placebo group had their first SBM. The SPS dose was titrated down during the study by nearly 50% of patients. Assessment of quality of life (QoL) by the constipation-related Patient Assessment of Constipation (PAC)-QoL questionnaire showed significant improvement in SPS-treated patients compared to the placebo group.
CONCLUSIONS: Treatment of chronic constipation with SPS improves bowel function, symptoms, and QoL and is well tolerated. The dose can be adjusted individually while maintaining benefit.

PMID 20179697
Guan-qun Chao, Shuo Zhang
A meta-analysis of the therapeutic effects of amitriptyline for treating irritable bowel syndrome.
Intern Med. 2013;52(4):419-24. Epub 2013 Feb 15.
Abstract/Text OBJECTIVE: We aimed to evaluate the efficacy of amitriptyline as a therapeutic option for irritable bowel syndrome (IBS) through a meta-analysis of randomized controlled trials.
METHODS: For the years from 1966 until May 2012, PubMed, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were searched for double-blind, placebo-controlled trials investigating the efficacy of amitriptyline in the management of IBS.
RESULTS: Four randomized, placebo-controlled clinical trials met our criteria and were included in the meta-analysis. The pooled relative risk for clinical improvement with amitriptyline therapy was 4.18 (95% CI: 2.00 to 8.77, p=0.0001).
CONCLUSION: It was thus concluded that amitriptyline exhibits a clinically and statistically significant control of IBS symptoms.

PMID 23411695
Megan Friedrich, Sarah E Grady, Geoffrey C Wall
Effects of antidepressants in patients with irritable bowel syndrome and comorbid depression.
Clin Ther. 2010 Jul;32(7):1221-33. doi: 10.1016/j.clinthera.2010.07.002.
Abstract/Text BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects up to 15% of community dwelling individuals. Psychiatric comorbidities, particularly symptoms of major depressive disorder (MDD), occur in up to 90% of patients with IBS.
OBJECTIVE: This article reviews the available literature on the use of antidepressants for both IBS and psychiatric depressive symptoms in patients with IBS.
METHODS: MEDLINE and International Pharmaceutical Abstracts (both, 1980-May 2010) were searched for English-language publications that involved antidepressant treatment of MDD in patients with IBS. The search terms were depression, irritable, bowel, treatment, and functional. The reference lists of key articles were searched for additional pertinent articles. Randomized controlled trials published in the past 10 years were given priority.
RESULTS: Of 46 articles identified by the literature search, 11 were included in the review: 4 studies of selective serotonin reuptake inhibitors (SSRIs), 4 of tricyclic antidepressants (TCAs), 1 comparing an SSRI and a TCA, 1 of the serotonin-norepinephrine reuptake inhibitor duloxetine, and a case report involving the tetracyclic antidepressant mirtazapine. Most of the identified studies excluded patients with a diagnosis of depression and/or anxiety. No controlled studies were identified in which the primary outcome was objective assessment of MDD symptoms in patients with IBS. Two of the SSRI studies, one of citalopram and the other of paroxetine, reported approximately 50% improvement in IBS symptoms (both studies, P = 0.01); the study of paroxetine reported a 30% improvement in scores on the Beck Depression Inventory (P = 0.01). The 2 studies of fluoxetine found no statistically significant benefit on IBS symptoms. TCAs were reported to have benefits on IBS symptoms, predominantly diarrhea. Only one of the TCA studies examined and found a significant improvement in depressive symptoms with desipramine 150 mg/d (P = 0.025). Both the open-label study of duloxetine and the case report involving mirtazapine found improvements in IBS and psychiatric symptoms.
CONCLUSIONS: The evidence for the benefit of antidepressant treatment in patients with IBS and comorbid depression was limited and contradictory. Some anti-depressants may help symptoms of IBS, although whether the same drugs and doses are associated with improvements in concomitant depressive symptoms remains to be elucidated.

2010 Excerpta Medica Inc. All rights reserved.
PMID 20678672
Abstract/Text BACKGROUND: The efficacy of unselected monoamine reuptake inhibitors (tricyclic antidepressants) in the treatment of patients with functional gastrointestinal disorders (FGD) has not been convincingly demonstrated. We investigated the efficacy of an antidepressant (mianserin) with a different receptor profile (combined 5-hydroxytryptamine-2 + 3 and alpha-2 antagonist) in FGD.
METHODS: After excluding patients with psychopathology and initial placebo responders from the study, eligible patients (n = 49) were randomized to 7 weeks of double-blind treatment with either mianserin, 120 mg/day, or placebo. Efficacy was assessed by using observer-completed ratings, the Global Improvement Scale, and patient self-ratings, Visual Analog Scale, and Disability Scales.
RESULTS: Patients taking mianserin reported less abdominal pain, symptoms of abdominal distress, and functional disability than those given placebo (p < 0.001). The efficacy was significant across different lengths of illness periods and types of functional disorder. There was no major change 4 weeks after tapering.
CONCLUSION: Mianserin may be an effective and well-tolerated pharmacologic short-term treatment for functional gastrointestinal disorders in patients with no clinical evidence of psychopathology.

PMID 8726297
P Nigam, K K Kapoor, C K Rastog, A Kumar, A K Gupta
Different therapeutic regimens in irritable bowel syndrome.
J Assoc Physicians India. 1984 Dec;32(12):1041-4.
Abstract/Text
PMID 6526796
J Labus, A Gupta, H K Gill, I Posserud, M Mayer, H Raeen, R Bolus, M Simren, B D Naliboff, E A Mayer
Randomised clinical trial: symptoms of the irritable bowel syndrome are improved by a psycho-education group intervention.
Aliment Pharmacol Ther. 2013 Feb;37(3):304-15. doi: 10.1111/apt.12171. Epub 2012 Dec 3.
Abstract/Text BACKGROUND: Evidence supports the effectiveness of cognitive behavioural approaches in improving the symptoms of the irritable bowel syndrome (IBS). Duration, cost and resistance of many patients towards a psychological therapy have limited their acceptance.
AIM: To evaluate the effectiveness of a psycho-educational intervention on IBS symptoms.
METHODS: Sixty-nine IBS patients (72% female) were randomised to an intervention or a wait-list control group. The IBS class consisted of education on a biological mind body disease model emphasising self-efficacy and practical relaxation techniques.
RESULTS: Patients in the intervention showed significant improvement on GI symptom severity, visceral sensitivity, depression and QoL postintervention and most of these gains were maintained at 3-month follow-up (Hedge's g = -0.46-0.77). Moderated mediation analyses indicated change in anxiety, visceral sensitivity, QoL and catastrophising due to the intervention had moderate mediation effects (Hedge's g = -0.38 to -0.60) on improvements in GI symptom severity for patients entering the trial with low to average QoL. Also, change in GI symptom severity due to the intervention had moderate mediation effects on improvements in QoL especially in patients with low to average levels of QoL at baseline. Moderated mediation analyses indicated mediation was less effective for patients entering the intervention with high QoL.
CONCLUSIONS: A brief psycho-educational group intervention is efficacious in changing cognitions and fears about the symptoms of the irritable bowel syndrome, and these changes are associated with clinically meaningful improvement in symptoms and quality of life. The intervention seems particularly tailored to patients with low to moderate quality of life baseline levels.

© 2012 Blackwell Publishing Ltd.
PMID 23205588
Alexander C Ford, Eamonn M M Quigley, Brian E Lacy, Anthony J Lembo, Yuri A Saito, Lawrence R Schiller, Edy E Soffer, Brennan M R Spiegel, Paul Moayyedi
Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis.
Am J Gastroenterol. 2014 Sep;109(9):1350-65; quiz 1366. doi: 10.1038/ajg.2014.148. Epub 2014 Jun 17.
Abstract/Text OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate.
METHODS: We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or "usual management," were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI).
RESULTS: The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or "usual management," sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial.
CONCLUSIONS: Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable.

PMID 24935275
A N Webb, R H Kukuruzovic, A G Catto-Smith, S M Sawyer
Hypnotherapy for treatment of irritable bowel syndrome.
Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005110. doi: 10.1002/14651858.CD005110.pub2. Epub 2007 Oct 17.
Abstract/Text BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder of unknown aetiology. Current pharmacological treatments have limited value. Hypnotherapy has been reported to have beneficial effects for IBS symptoms.
OBJECTIVES: To evaluate the efficacy of hypnotherapy for the treatment of irritable bowel syndrome.
SEARCH STRATEGY: Published and unpublished randomised clinical trials and quasi-randomised clinical trials were identified through structured searches of MEDLINE (1966 to March 2006), EMBASE (1980 to March 2006), PsycINFO (1806 to March 2006), CINAHL (Cumulative Index to Nursing and Allied Health Literature, 1982 to March 2006), AMED (Allied and Complementary Medicine Database, 1985 to March 2006) and The Cochrane Central Register of Controlled trials. Conference proceedings from Digestive Disease Week (1980 to 2005) were also searched.
SELECTION CRITERIA: Eligible studies included all randomised and quasi-randomised clinical studies comparing hypnotherapy for the treatment of irritable bowel syndrome with no treatment or another therapeutic intervention.
DATA COLLECTION AND ANALYSIS: All studies were evaluated for eligibility for inclusion. Included studies were assessed for quality and data were extracted independently by four authors. The primary outcome measure of interest was the overall bowel symptom severity score which combines abdominal pain, diarrhoea or constipation and bloating. Secondary outcomes included abdominal pain, diarrhoea, constipation, bloating, quality of life, patient's overall assessment of well-being, psychological measures as per validated questionnaires, and adverse events.
MAIN RESULTS: Four studies including a total of 147 patients met the inclusion criteria. Only one study compared hypnotherapy to an alternative therapy (psychotherapy and placebo pill), two studies compared hypnotherapy with waiting-list controls and the final study compared hypnotherapy to usual medical management. Data were not pooled for meta-analysis due to differences in outcome measures and study design. The therapeutic effect of hypnotherapy was found to be superior to that of a waiting list control or usual medical management, for abdominal pain and composite primary IBS symptoms, in the short term in patients who fail standard medical therapy. Harmful side-effects were not reported in any of the trials. However, the results of these studies should be interpreted with caution due to poor methodological quality and small size.
AUTHORS' CONCLUSIONS: The quality of the included trials was inadequate to allow any conclusion about the efficacy of hypnotherapy for irritable bowel syndrome. More research with high quality trials is needed.

PMID 17943840
Vivien Miller, Peter J Whorwell
Hypnotherapy for functional gastrointestinal disorders: a review.
Int J Clin Exp Hypn. 2009 Jul;57(3):279-92. doi: 10.1080/00207140902881098.
Abstract/Text Patients with functional gastrointestinal disorders, such as irritable bowel syndrome, functional dyspepsia, and noncardiac chest pain, can suffer from a range of severe symptoms that often substantially erode quality of life. Unfortunately, these conditions are notoriously difficult to treat, with many patients failing to improve despite being prescribed a wide variety of conventional medications. As a consequence, the potential benefits of hypnotherapy have been explored with evidence that this approach not only relieves symptoms but also appears to restore many of the putative psychological and physiological abnormalities associated with these conditions toward normal. These observations suggest that this form of treatment has considerable potential in aiding the management of functional gastrointestinal disorders and should be integrated into the ongoing medical care that these patients are receiving.

PMID 19459089
Christopher J Black, Elyse R Thakur, Lesley A Houghton, Eamonn M M Quigley, Paul Moayyedi, Alexander C Ford
Efficacy of psychological therapies for irritable bowel syndrome: systematic review and network meta-analysis.
Gut. 2020 Aug;69(8):1441-1451. doi: 10.1136/gutjnl-2020-321191. Epub 2020 Apr 10.
Abstract/Text OBJECTIVES: National guidelines for the management of irritable bowel syndrome (IBS) recommend that psychological therapies should be considered, but their relative efficacy is unknown, because there have been few head-to-head trials. We performed a systematic review and network meta-analysis to try to resolve this uncertainty.
DESIGN: We searched the medical literature through January 2020 for randomised controlled trials (RCTs) assessing efficacy of psychological therapies for adults with IBS, compared with each other, or a control intervention. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic, with a 95% CI to summarise efficacy of each comparison tested, and ranked by therapy according to P score.
RESULTS: We identified 41 eligible RCTs, containing 4072 participants. After completion of therapy, the psychological interventions with the largest numbers of trials, and patients recruited, demonstrating efficacy included self-administered or minimal contact cognitive behavioural therapy (CBT) (RR 0.61; 95% CI 0.45 to 0.83, P score 0.66), face-to-face CBT (RR 0.62; 95% CI 0.48 to 0.80, P score 0.65) and gut-directed hypnotherapy (RR 0.67; 95% CI 0.49 to 0.91, P score 0.57). After completion of therapy, among trials recruiting only patients with refractory symptoms, group CBT and gut-directed hypnotherapy were more efficacious than either education and/or support or routine care, and CBT via the telephone, contingency management, CBT via the internet and dynamic psychotherapy were all superior to routine care. Risk of bias of trials was high, with evidence of funnel plot asymmetry; the efficacy of psychological therapies is therefore likely to have been overestimated.
CONCLUSIONS: Several psychological therapies are efficacious for IBS, although none were superior to another. CBT-based interventions and gut-directed hypnotherapy had the largest evidence base and were the most efficacious long term.
TRIAL REGISTRATION NUMBER: The study protocol was published on the PROSPERO international prospective register of systematic reviews (registration number CRD 42020163246).

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
PMID 32276950

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