No job name

R E V I E W S E R I E S : A D VA N C E S I N C L I N I C A L P R A C T I C E jgh_6120 691.699 Irritable bowel syndrome: Epidemiology, diagnosis and
treatment: An update for health-care practitioners
Oliver Grundmann* and Saunjoo L Yoon†
*College of Pharmacy, Department of Medicinal Chemistry, and †College of Nursing, Department of Adult and Elderly, University of Florida, Key words
Irritable bowel syndrome (IBS), a chronic gastrointestinal disorder, affects from 3–20% of bowel disease, irritable bowel syndrome.
the US population, depending on sociocultural and comorbid factors. IBS is characterizedby a symptom complex of abdominal pain and abnormal bowel habits that present as Accepted for publication 2 September 2009.
diarrhea or constipation, and general physical weakness in the absence of abnormal mor- Correspondence
phological, histological or inflammatory markers. The main diagnostic Rome III criteria as Oliver Grundmann, Department of Medicinal established by international professional organizations are based on exclusion criteria and Chemistry, College of Pharmacy, University of the occurrence and rate of symptoms. Because the pathophysiology and causes of IBS are Florida, P.O. Box 100485, Gainesville, FL poorly understood, treatment approaches are mainly focused on symptom management to maintain everyday functioning and improve quality of life for persons with IBS. Themainstay of intervention is pharmacological treatment with antispasmodics and antidiar-rheals for diarrhea, prokinetics and high-fiber diets for constipation, and supportive therapywith low-dose antidepressants to normalize gastrointestinal motility. Other interventionsinclude lifestyle and dietary changes, psychotherapy, herbal therapies and acupuncture. Thepurpose of this review is to critically assess benefits and risks of current treatmentapproaches as well as promising complementary and alternative therapies.
overview of IBS epidemiology, symptoms and diagnostic criteria,and current treatment approaches.
In the last two decades, irritable bowel syndrome (IBS) has gainedconsiderable attention in the health-care field due to its increas-ingly high prevalence, sometimes debilitating effects and diverse Epidemiology
symptom representation.1 IBS belongs to a group of chronic gas-trointestinal (GI) diseases referred to as functional bowel disorders Assessment of the prevalence of IBS has been complicated by the (FBD) as classified by the Rome foundation,2 an international clarity of assessment criteria to differentiate between various FBD organization dedicated to research and education in the field of and other chronic GI disorders. The last comprehensive review of the prevalence and epidemiology of IBS in North America, in The World Health Organization (WHO) has given IBS its own which five population-based prevalence studies were evaluated, classification in its 10th revision of the International Classification was conducted in 2002.5 An important factor in diagnosing IBS is of Diseases (ICD-10), recognizing the significance of this syn- the set of criteria utilized, such as the Rome criteria6 and the drome.3 The first diagnostic evaluation of IBS was introduced with Manning questionnaire.4 In some cases, the two evaluation tools the Manning criteria in the 1970s, which utilized a 15-symptom were directly compared in the studies and provided a more diverse questionnaire to differentiate between IBS and what were then dataset, depending on how many scale criteria a person had to referred to as organic abdominal diseases.4 Over the past decade, meet in order to be diagnosed with IBS.
advances have been made in classifying various chronic disease The range of prevalence was from 3–20%, with most studies states of FBD to create differential diagnosis criteria as well as between 10% and 15% (mean of all 13 studies was 11.6% with a exploring new treatments for a group of widespread disorders.
standard deviation of 4.6%). Interestingly, there is a higher ratio of Although a precise definition of IBS is still controversial on the women who develop IBS compared to men (ratio of 2:1) although basis of a functional or an organic disorder with symptoms that there were also differences observed among studies. Age-related differentiate it from other FBD, current efforts underline that IBS onset of IBS symptoms occurred predominantly in patients requires attention from a health-care professional.1 The purpose of younger than 45 years but prevalence rose again in the elderly. The this clinical review is to provide health-care practitioners with an subclassification of IBS as either IBS-D (IBS with predominant Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd diarrhea) with 5.0–5.5%, IBS-C (IBS with predominant constipa- symptom criteria (e.g. instead of using self-reported diagnosis) tion) with 5.2–5.4% or IBS-M (IBS with alternating constipation and diarrhea, mixed IBS) with 5.2% was evaluated by two The population studies demonstrate the diversity of IBS based population-based studies.7,8 Other factors that have a significant on ethnicity, age and culture (e.g. diet, access to health-care pro- impact on the development of IBS are health status, comorbid viders) and the importance of evaluation criteria that impact choice conditions,9 diet10 and mental health.11,12 of therapy.8,23 Diet, as part of a cultural factor, has been studied in Recent study findings in Korea,13 Greece,14 Malaysia,15 Fin- relation to IBS treatment. Simple changes in diet may improve land16 and France17 showed variations in prevalence of IBS and symptoms (most likely reductions in fat consumption that lead to distribution of the subclassification. In the Korean study, approxi- bloating) for some patients, while symptoms actually worsen for mately half of the patients diagnosed with IBS first experienced others if the diet is rich in fiber, wheat or carbohydrates (specifi- symptoms before the age of 40 years with approximately even cally diarrhea-predominant IBS).10,24 As mentioned before, these distribution between women and men.13 Although prevalence of studies were mainly conducted in small patient populations and IBS was not reported, these researchers evaluated the subtype of larger clinical studies are required to confirm these findings.
IBS and found that more than half of IBS patients suffered fromconstipation-predominant IBS. A study with young Malaysian Symptoms, differential diagnosis
adults (mean age 22 Ϯ 1.8 years) showed a prevalence rate of and pathophysiology
15.8% with a female-to-male ratio of 1.7:1.15 Subclassification ofIBS also resulted in approximately 75% of patients diagnosed with Symptoms of IBS have been studied and its criteria have been IBS-C, with much lower IBS-M type occurrence. This outcome is refined over the past decades, and guidelines for differential diag- surprising in light of other studies conducted in Asian populations nosis have been established by various professional societies, that frequently reported a lower prevalence rate of IBS.18–20 One including the British Society of Gastroenterology,25 the American reason for this discrepancy might involve diagnostic criteria College of Gastroenterology26 and the American Gastroenterologi- because use of Manning and Rome I criteria frequently resulted in cal Association.27 Diagnostic criteria for IBS are now based on a lower rate of a positive IBS diagnosis.1 In a Finnish study, the evaluating present symptoms to distinguish it from other GI various diagnostic criteria were compared and applied to an disorders globally and from FBD, specifically. In general, IBS is obtained dataset of patients diagnosed with IBS.16 The prevalence characterized as a functional disorder of the GI tract associated as evaluated by Manning and Rome I and II criteria varied from with abdominal pain and altered bowel activity but lacking any 5.1–16.2%. Use of the Manning criteria in this study resulted in a pathological organic changes. This distinguishes it from inflam- significantly higher prevalence rate than the Rome criteria. The matory bowel disease (IBD), which presents with increased reported age of IBS onset was evenly distributed throughout the phagocyte-specific protein in the feces, in that IBS does not cause study population, with a slightly higher prevalence in women than inflammation as can be assessed with a differential blood test and men. It appeared that diarrhea was predominantly observed in this fecal markers, observation of ulcers, or other organic damage to population but no subclassification has been made.
the GI tract.28 Furthermore, the absence of organic pathophysi- French researchers utilized the Rome I criteria to conclude that ological changes distinguishes IBS from many other GI disorders prevalence of IBS was 4.0% with a female-to-male ratio of 2.3:1 such as Crohn’s disease, chronic inflammation of the distal GI and equal distribution of IBS-D, IBS-C and IBS-M subclassifica- tract caused by certain Escherichia coli strains with high genetic tion throughout the study population.17 Prevalence of IBS symp- predisposition,29 and celiac disease which causes gluten-induced toms ranged from 3.2–4.3% between the different age groups; the auto-inflammatory degeneration of the small intestines.30 lowest prevalence was in younger adults 18–24 years of age. In a Despite these differences, diagnosis of IBS is based on recent study conducted in Greece, prevalence of IBS was 15.7% symptom representation and a thorough initial evaluation of any based on the Rome II diagnostic criteria.14 Constipation- organic abnormalities. Symptoms that predominate in IBS are predominant IBS was the most common among IBS subtypes, unspecific abdominal pain or discomfort that recurs infrequent followed by diarrhea-predominant IBS. More women than men bowel movements with periods of increased or decreased activity, were affected, with a ratio of 1.3:1 with reported onset of IBS alleviation of pain and discomfort with defecation, and onset of symptoms with changes in stool frequency and appearance. These Other important comorbidity factors that contribute to develop- are the symptoms most frequently employed in making a differ- ment of IBS as a functional disorder are depression, anxiety and ential diagnosis in conjunction with the Rome II and new Rome III insomnia, which should be evaluated by health-care providers to derive the differential diagnosis.11,14 The most common psychiatric Diarrhea (IBS-D) and constipation (IBS-C) are the two domi- disorder associated with IBS is depression, with a prevalence of nant subtypes of IBS; a mixed subtype (IBS-M) occurs least fre- approximately 30% in IBS patients compared to only 18% in a quently. The Rome foundation classifies IBS as an FBD with the control population.11 Anxiety is also commonly encountered as subclassification letter C16 (see Table 1). The WHO grouped IBS a comorbid condition in IBS, with 16% affected compared to in its ICD-10 revision in Chapter XI under ‘Diseases of the Diges- controls at a rate of 6%.11 There also appears to be a correlation tive System’ and further into ‘Other Diseases of Intestines’ and between anxiety and depressive disorders and the severity of IBS K58 ‘Irritable Bowel Syndrome’, which includes K58.0 ‘Irritable symptoms as increases in comorbidity have been found between bowel syndrome with diarrhea’ and K58.9 ‘Irritable bowel syn- these diagnoses and worsening of IBS symptoms.21 Findings regarding association of comorbid conditions including psychiat- The slow onset of IBS over weeks and months shows a strong ric disorders with IBS may be strengthened by tightly controlled correlation with stress disorders such as depression and anxiety31 Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Comparison between Rome II and Rome III criteria The limbic system in conjunction with paralimbic structures connects the gut with the CNS through the autonomic nervous Comparison of Rome III to Rome II criteria6
system in a bidirectional way. This allows transmission of emo- tional states from the CNS to the gut and perception of GI changes(pain, contractions, bloating) to the CNS.37,38 Independent of afferent connections from the CNS, the gut is able to release the neurotransmitters serotonin and acetylcholine as part of the enteric nervous system (ENS).39 The main neurotransmitter that regulates GI motility is serotonin (5-HT), which is released from entero- chromaffin cells in the GI mucosa to stimulate acetylcholine release that initiates GI motility.40 The primary serotonin receptors involved in ENS transmissions are the 5-HT3 and 5-HT4 receptors, each with specific distribution patterns.41–43 While 5-HT3 receptors signal changes in intestinal motility to the ENS and serve as the main neurotransmitter for efferent nerves connecting to the CNS, 5-HT4 receptors are exclusively presynaptic and therefore serve as interneurons to transmit a signal to effector acetylcholine neurons.
Serotonin signaling is terminated by a specific serotonin reuptake transporter (SERT) located on enterocytes within the intestinal mucosa.44 It has been shown that a decrease in SERT consistently leads to dysfunction of GI motility in animals and in humans through increased serotonin concentrations.45 Elevated serotonin concentrations then constantly stimulate 5-HT3 and 5-HT4 recep- tors leading to dysregulated contractions and dilations of the intestinal tract. Attenuation of this signaling cascade is employed for treatment of IBS and various other GI disorders. Although the precise pathophysiology of IBS is still unknown, the above- mentioned factors contribute to development of this chronic Current treatment approaches
Irritable bowel syndrome treatment approaches depend on symptom representation and comorbid conditions such as lifestyle, diet and stress disorders. Because IBS classification is based on thepredominant symptom of diarrhea, constipation or mixed IBS, †Criterion fulfilled for the last 3 months with symptom onset at least treatment focuses on normalizing GI motility. Recently, the Task Force on Irritable Bowel Syndrome of the American College of ‡‘Discomfort’ means an uncomfortable sensation not described as pain.
Gastroenterology has published a detailed systematic review on the management of IBS.26 An important consideration highlightedin IBS treatment guidelines of the British Society of Gastroenter-ology is the influence of placebo on the outcome.25 The placeboeffect during the first weeks of therapy is three times higher (46%) or can follow a GI infection,32 in which case it is classified as than the average placebo effect with drug therapy for other condi- post-infectious IBS (PI-IBS). In contrast to patients without a prior tions (16%). It is also higher in patients who respond well to GI infection, PI-IBS patients can present with altered gut immune health-care provider–patient interactions and reassurance that their function represented by an increase in lymphocyte infiltrates and condition, although chronic in nature, is not a grave prognosis25,36 inducible nitric oxide synthase in the feces.33,34 Following the and can be treated. The confounding variable of a psychological Rome criteria, a patient can be diagnosed with IBS by considering disorder presents with a lower placebo effect.
the family and clinical history (colon cancer, onset of symptomslater than aged 50 years), symptom representation with a gradual Lifestyle and dietary changes
onset and consistency, no specific warning signs indicative of aspecific pathophysiology (including rectal bleeding, anemia, Before pharmacological treatment is considered, lifestyle and diet weight loss, fever) and normal laboratory results. Diagnosis with should be evaluated as potential triggers for IBS symptoms. Lack consideration of stress disorders and explanation to the patient of exercise, food deficiencies, lack or excess of dietary fiber intake, about the relationship between altered central nervous system and lack of suitable times for defecation should be evaluated as (CNS) signaling and IBS development may aid in establishing determining factors that contribute to the development of IBS, positive health-care provider–patient rapport with consistently specifically constipation-predominant IBS.25 Thus, an increase in dietary fibers and regular exercise might benefit constipated IBS Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd patients.46 Excessive caffeine consumption, indigestible carbohy- the exact mechanism for development of IBS is unknown. Phar- drates and high lactose intake have been found to contribute to macological treatment of constipation-predominant IBS focuses diarrhea-predominant IBS.10,24 In general terms, a stepwise food on prokinetics that shorten transit time in the intestines and anti- exclusion approach should be tried if the symptoms are mild to spasmodics to alleviate cramping as a result of intestinal wall moderate.47 The evaluation of probiotics to treat IBS has been pressure. A high-fiber diet might improve symptoms in some summarized in meta-analytic studies that showed modest improve- patients, but mixed results have been shown in clinical studies.25,27 ments for bloating, abdominal pain and bowel movement difficul- Prokinetics are used to enhance intestinal contractions and ties. No specific probiotic strain was found to be superior to facilitate the movement of fecal matter by acting as dopamine another, and often combinations of strains were used.46,48 antagonists, 5-HT3 antagonists and/or 5-HT4 agonists. Despiteinconsistent benefits to IBS-C patients, they are widely used and Psychotherapy and
increase GI motility with concomitant increase in secretory activ- psychopharmacological treatment
ity and effects as visceral analgesics.56 Tegaserod is the only pro-kinetic drug approved by the US Food and Drug Administration The impact of various forms of psychotherapy (e.g. cognitive for the treatment of IBS, but it was restricted in 2007 due to risk of behavioral therapy, dynamic psychotherapy, hypnotherapy, bio- cardiovascular ischemic events.57 Other prokinetics commonly feedback and relaxation therapy) on IBS has been evaluated.
used in clinical practice without specific IBS indication are dom- According to guidelines of the British Society of Gastroenterol- peridone, metoclopramide, cisapride and renzapride.56 Newly ogy25 and the American Gastroenterology Association,27 psycho- approved in 2008 for treatment of IBS-C in women is the laxative therapeutic interventions are usually reserved for severe forms of lubiprostone, which acts as a chloride channel activator that IBS that show high incidence of a comorbid psychological dis- increases water secretion into the feces.58,59 order49 or if a known comorbidity with a depressive or anxiety A meta-analysis of clinical trials with antispasmodics revealed disorder exists. The most effective psychotherapeutic interventions that the clinical benefit of cimetropium, pinaverium, hyoscine and were hypnotherapy and stress management over the course of otilonium was highest whereas studies with pirenzepine and 6 weeks to 6 months in patients with IBS-D or IBS-M. Concomi- propinox favored the placebo treatment over the actual drug.60 As tant treatment of diagnosed depression or anxiety disorders expected with the anticholinergic antispasmodics, the most through psychotherapy and pharmacological treatment often helps common adverse effects were dry mouth, dizziness and blurred vision; effects about which patients must be clearly informed. In A recent meta-analysis and systematic review showed that the addition, the prescribed antispasmodic should be given on an heterogeneity of psychotherapeutic treatment results in a 25% as-needed basis with a maximum of three times per day for acute chance that a patient will benefit from any type of psychotherapy,49 spastic episodes.27 Antispasmodics will reduce GI motility and while hypnotherapy and stress management had a higher rate therefore need to be given in conjunction with a prokinetic or of success with 52% and 67%, respectively.52 In the same laxative in order to increase GI motility. Antispasmodics are meta-analysis,49 the use of both tricyclic (TCA) and selective sero- mainly used in both IBS-C and IBS-D to reduce abdominal pain tonin reuptake inhibitor (SSRIs) antidepressants in the treatment of IBS were compared. Antidepressant treatment often requires While the goal of IBS-C treatment is an increase in GI motility, patient counseling, particularly in the first 3–4 weeks of treatment, the opposite is necessary for patients predominantly affected by because side effects are pronounced, with a delayed onset of anti- IBS-D. Diarrhea-associated symptoms often include a social depressant action. While TCAs act both on norepinephrine and component, which might impact the patient’s ability to maintain a serotonin transmission with varying specificities, SSRIs specifi- normal daily routine or interact with other people because of cally increase serotonin concentrations in the CNS. Both TCAs constant worry of having loose stool. A more severe consequence and SSRIs demonstrated a treatment benefit in IBS symptoms with of chronic diarrhea is malnutrition of vitamins and other nutrients.
a success rate in symptom reduction of 58% and 55%, respec- Commonly used pharmacological treatments for IBS-D are opioid tively.49 SSRIs, associated with fewer side effects than TCAs, may agents, 5-HT3 antagonists, and anticholinergic agents. Loperamide also prove beneficial in treating anxiety disorders although they do is an opioid agonist that acts on m-receptors of the myenteric not alleviate abdominal bloating or reduction in visceral pain sen- plexus in the large intestines without being absorbed or causing sitivity.53,54 While benzodiazepines are more frequently prescribed CNS effects after oral administration.61 Loperamide, commonly for anxiety disorders, their effectiveness in symptom alleviation used for short-term diarrhea due to bacterial GI infections, should for IBS is questionable.27 Therefore, use of TCAs in doses below only be given in low doses as needed to patients with IBS-D. Dose regular antidepressant effectiveness has become a mainstay of IBS adjustment should occur if concomitant GI motility inhibitors such because it alters GI motility (normalization of motility and secre- as anticholinergics are given. Codeine can also be given to slow GI tion as well as reduction in visceral pain sensitivity)52 which has motility but is associated with sedation and drug dependency recently been established through meta-analysis of clinical trials.55 Antagonism of 5-HT3 receptors in the ENS has been shown to Pharmacological treatment
inhibit GI motility and benefit abdominal pain by reducing visceralsensitivity in patients with IBS-D predominance.63 Ondansetron, After lifestyle and diet changes have failed to alleviate or resolve granisetron, alosetron and cilansetron are all selective 5-HT3 IBS symptoms, the most common treatment approach is pharma- receptor antagonists frequently prescribed for IBS-D as well as cotherapy. This follows the predominant symptom representation for other conditions such as vomiting and nausea associated with and is therefore symptomatic (not causative) treatment, because chemotherapy.64 Although ondansetron was the first 5-HT3 Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd antagonist to be discovered, the predominant treatment option for cal trials of peppermint oil preparations with a placebo.60,75 These IBS-D is alosetron, due to its preferred side-effect profile and studies are based on the traditional use of preparations from pep- better reduction in visceral sensitivity.65 The rare but severe effects permint leaves for the alleviation of stomach upset, which has been of ischemic colitis and constipation led to restricted use of alos- supported by other research findings of smooth muscle relaxation etron for the treatment of IBS-D in women who failed to respond effect from use of both peppermint oil and the isolated compound to other treatments. The recommendation is to start with a reduced menthol.76,77 This is most likely attributable to the effect on dose of 1 mg once daily and then increase if needed to 1 mg twice calcium- and potassium-dependent ion channels on enterocytes.
daily. Alosetron has an absolute contraindication for patients with These clinical studies demonstrated that supplementation of pep- permint oil, in addition to pharmacological standard treatments, The anticholinergic antispasmodics are frequently used to was of benefit to both IBS-C and IBS-D patients.
reduce abdominal pain, visceral sensitivity and GI motility.
Acupuncture, which has been used as a therapeutic treatment in Whereas unspecific anticholinergics such as hyoscine or pinav- Chinese traditional medicine for centuries, has gained significant erium are used to treat both IBS-C and IBS-D, specific muscarinic attention over the past decades in Western medicine. A recent M3 receptor antagonists such as darifenacin and zamifenacin meta-analysis of a few small clinical trials involving the effect of might provide a more specific treatment approach.67,68 Although acupuncture treatment in patients with IBS included only studies commonly used for treatment of overactive bladder and urinary that used actual acupuncture versus sham acupuncture, any other incontinence, these drugs are frequently used to reduce GI motility active interventions, or no treatment (negative control) to alleviate in IBS-D without currently being approved for this indication.
IBS symptoms.78 The meta-analysis revealed that the effects of Some drugs currently in clinical development target the treatment acupuncture on IBS symptoms were variable and did not differ of visceral pain in IBS and include specific b3-adrenoreceptor significantly from the sham acupuncture treatment or any other agonists, corticotropin-releasing factor (CRF)-receptor antago- interventions.78 This may be due to inconsistencies in study nists, k-opioid receptor agonists and pregabalin. These new drugs designs and possible inclusion of patients who were not thor- showed promising results that may soon offer new options for oughly diagnosed with IBS prior to treatment. More research with consistency in study protocol, standardized outcome measures andtight sampling criteria are needed to determine whether acupunc-ture is a beneficial treatment for IBS symptoms.79 Complementary and
alternative therapies

Implications and future outlook
The American Gastroenterological Association technical review The scientific evidence supports the importance of recognizing for IBS27 mentions that complementary and alternative therapies IBS as a clinically significant GI disorder that merits both diag- have been used continually and reported benefit in persons with nostic evaluation and an individual treatment approach based on IBS although the effectiveness of the therapies has not been clini- cally well studied. A Cochrane review of herbal medicines for the Because symptoms are rather unspecific and often triggered by treatment of IBS70 identified several well-designed clinical studies stress or other life events, it is crucial to assure the patient that that showed improvement of IBS symptoms. One study employing her/his condition is benign and can be treated with appropriate a variety of Chinese herbal medicines, given alone or in a fixed treatment options. In choosing treatments, the patient should also combination, showed significant improvement of various IBS be made aware of potential adverse effects associated with low- symptoms over a placebo treatment that extended beyond the end dose tricyclic antidepressants or careful dosing schemes for antidi- arrheal and antispasmodic agents. A comfortable patient–provider Other herbal preparations included in the Cochrane review were relationship is a good basis for an open discussion about lifestyle a Tibetan herbal formula sold as Padma Lax (Padma, Schwerzen- changes and often allows the patient to be more forthcoming about bach, Switzerland) and a combination of herbs under the trade otherwise socially restrictive topics such as bloating and diarrhea.
In this context, the patient should understand that pharmacological Germany). Treatment with these preparations were found to mark- treatment will help alleviate these symptoms and careful, tempo- edly improve IBS symptoms.72,73 Padma Lax significantly reduced rary dose adjustment can be used for specific purposes in social the severity of abdominal pain and increased transit time compared interactions. In most primary care settings, psychotherapeutic to placebo in patients with predominant IBS-C symptoms. Padma intervention is not necessary unless severe underlying depressive Lax capsules, containing 13 standardized herbal plant extracts, or anxiety disorders are suspected that require referral to a spe- can be given orally. Iberogast, a liquid comprised of standardized cialist. The health-care provider should provide the patient with extracts from nine herbal remedies, is given orally three times information and reassurance that her/his condition is taken seri- daily. The overall rating of IBS symptoms, such as abdominal ously and can be appropriately treated.
pain, improved under Iberogast treatment compared to a placebo.
Although the pathophysiology of IBS is still poorly understood, It has been suggested that a combination of certain herbs may act the future outlook for treatment of IBS is focused on modulation of synergistically on serotonin and acetylcholine receptors as with innervating neurotransmitters in intestinal motility. Considerable Iberogast in isolated human intestines.74 Other alternative treat- investigation into a variety of new treatment approaches with both ments frequently used by patients suffering from IBS are pepper- synthetic and traditional medicines is promising. Newer serotonin mint oil and acupuncture. The use of peppermint oil has been receptor modulators focus on either antagonizing specific subtype evaluated through two meta-analysis studies that compared clini- receptors of 5-HT3 or serve as agonists on 5-HT4 receptors while Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Establish diagnosis
Rome II or
Rome III criteria
Develop relationship
Address patient
Explanation and
Consider referral
reassurance of
to psychotherapist
prognosis and
or psychiatrist
dietary advice
CAM as add-on
Pharmacological treatment
treatment options
Flow chart for diagnosis, patient–health-care provider relationship, and treatment options in IBS (based on Jones et al. with modifications).25 CAM, complementary and alternative medicine.
Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd simultaneously reducing serious adverse effects such as ischemic 15 Tan YM, Goh KL, Muhidayah R, Ooi CL, Salem O. Prevalence of colitis. The use of low-dose TCAs and SSRIs is targeted toward irritable bowel syndrome in young adult Malaysians: a survey pain relief and normalization of GI motility by acting on both among medical students. J. Gastroenterol. Hepatol. 2003; 18:
norepinephrine and/or serotonin neurotransmission. There is pre- 16 Hillila MT, Farkkila MA. Prevalence of irritable bowel syndrome clinical and clinical evidence to support the use of a2 and b3 according to different diagnostic criteria in a non-selected adult adrenergic receptor agonists for disturbed GI motility and pain population. Aliment. Pharmacol. Ther. 2004; 20: 339–45.
perception. Antagonists at neuropeptide (mainly neurokinin and 17 Bommelaer G, Dorval E, Denis P et al. Prevalence of irritable bowel corticotrophin-releasing hormone) receptors are currently evalu- syndrome in the French population according to the Rome I criteria.
ated for pain perception and reduction of nociception and visceral Gastroenterol. Clin. Biol. 2002; 26: 1118–23.
pain in patients with IBS.79 Although some of the preclinical data 18 Longstreth GF, Wolde-Tsadik G. Irritable bowel-type symptoms in for these agents were promising, clinical data are still lacking or HMO examinees. Prevalence, demographics, and clinical correlates.
inconsistent. Approaches that influence the flow of ions across the Dig. Dis. Sci. 1993; 38: 1581–9.
epithelial cell layer in the intestines have been translated in the 19 Danivat D, Tankeyoon M, Sriratanaban A. Prevalence of irritable new drug lubiprostone, which acts through chloride channels to bowel syndrome in a non-Western population. BMJ (Clin. Res. Ed.)
1988; 296 (6638): 1710.
increase water secretion into the lumen and therefore can be used 20 Kwan AC, Hu WH, Chan YK, Yeung YW, Lai TS, Yuen H.
as a laxative in IBS-C patients. Other drugs acting in a similar Prevalence of irritable bowel syndrome in Hong Kong. J. manner are currently being investigated and show some promising Gastroenterol. Hepatol. 2002; 17: 1180–6.
results in preliminary animal models and small clinical trials.
21 Drossman DA, Morris CB, Schneck S et al. International survey of patients with IBS: symptom features and their severity, health status, References
treatments, and risk taking to achieve clinical benefit. J. Clin.
2009; 43: 541–50.
1 Longstreth GF. Definition and classification of irritable bowel 22 Whitehead WE, Palsson O, Jones KR. Systematic review of the syndrome: current consensus and controversies. Gastroenterol. Clin. comorbidity of irritable bowel syndrome with other disorders: what North Am. 2005; 34: 173–87.
are the causes and implications? Gastroenterology 2002; 122:
2 Drossman DA. Introduction. The Rome Foundation and Rome III.
Neurogastroenterol. Motil. 2007; 19: 783–6.
23 Stewart WF, Liberman JN, Sandler RS et al. Epidemiology of 3 WHO. International Statistical Classification of Diseases and constipation (EPOC) study in the United States: relation of clinical Related Health Problems, 10th edn. Geneva, Switzerland: World subtypes to sociodemographic features. Am. J. Gastroenterol. 1999; 94: 3530–40.
4 Manning AP, Thompson WG, Heaton KW, Morris AF. Towards 24 Austin GL, Dalton CB, Hu Y et al. A very low-carbohydrate diet positive diagnosis of the irritable bowel. BMJ 1978; 2 (6138): 653–4.
improves symptoms and quality of life in diarrhea-predominant 5 Brandt LJ, Bjorkman D, Fennerty MB et al. Systematic review on irritable bowel syndrome. Clin. Gastroenterol. Hepatol. 2009; 7:
the management of irritable bowel syndrome in North America. Am. J. Gastroenterol. 2002; 97 (11 Suppl.): S7–26.
25 Jones J, Boorman J, Cann P et al. British Society of 6 Drossman DA, Douglas A, eds. Rome III: The Functional Gastroenterology guidelines for the management of the irritable Gastrointestinal Disorder, 3rd edn. McClean, VA, USA: Degnon bowel syndrome. Gut 2000; 47 (Suppl. 2): ii1–19.
26 Brandt LJ, Chey WD, Foxx-Orenstein AE et al. An evidence-based 7 Thompson WG, Irvine EJ, Pare P, Ferrazzi S, Rance L. Functional position statement on the management of irritable bowel syndrome.
gastrointestinal disorders in Canada: first population-based survey Am. J. Gastroenterol. 2009; 104 (Suppl 1): S1–35.
using Rome II criteria with suggestions for improving the 27 Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA questionnaire. Dig. Dis. Sci. 2002; 47: 225–35.
technical review on irritable bowel syndrome. Gastroenterology 8 Talley NJ, Zinsmeister AR, Melton LJ 3rd. Irritable bowel syndrome 2002; 123: 2108–31.
in a community: symptom subgroups, risk factors, and health care 28 Foell D, Wittkowski H, Ren Z et al. Phagocyte-specific S100 utilization. Am. J. Epidemiol. 1995; 142: 76–83.
proteins are released from affected mucosa and promote immune 9 Cash BD, Chey WD. Diagnosis of irritable bowel syndrome.
responses during inflammatory bowel disease. J. Pathol. 2008; 216:
Gastroenterol. Clin. North Am. 2005; 34: 205–20.
10 Lea R, Whorwell PJ. The role of food intolerance in irritable bowel 29 Olbe L. Concept of Crohn’s disease being conditioned by four main syndrome. Gastroenterol. Clin. North Am. 2005; 34: 247–55.
components, and irritable bowel syndrome being an incomplete 11 Palsson OS, Drossman DA. Psychiatric and psychological Crohn’s disease. Scand. J. Gastroenterol. 2008; 43: 234–41.
dysfunction in irritable bowel syndrome and the role of 30 Verdu EF, Armstrong D, Murray JA. Between celiac disease and psychological treatments. Gastroenterol. Clin. North Am. 2005; 34:
irritable bowel syndrome: the ‘no man’s land’ of gluten sensitivity.
Am. J. Gastroenterol. 2009; 104: 1587–94.
12 Cash BD, Chey WD. Irritable bowel syndrome—an evidence-based 31 Mayer EA, Craske M, Naliboff BD. Depression, anxiety, and the approach to diagnosis. Aliment. Pharmacol. Ther. 2004; 19:
gastrointestinal system. J. Clin. Psychiatry 2001; 62 (Suppl. 8):
13 Park JM, Choi MG, Kim YS et al. Quality of life of patients with 32 Spiller R, Campbell E. Post-infectious irritable bowel syndrome.
irritable bowel syndrome in Korea. Qual. Life. Res. 2009; 18:
Curr. Opin. Gastroenterol. 2006; 22: 13–17.
33 O’Sullivan M, Clayton N, Breslin NP et al. Increased mast cells in 14 Katsinelos P, Lazaraki G, Kountouras J et al. Prevalence, bowel the irritable bowel syndrome. Neurogastroenterol. Motil. 2000; 12:
habit subtypes and medical care-seeking behaviour of patients with irritable bowel syndrome in Northern Greece. Eur. J. Gastroenterol. 34 Spiller RC, Jenkins D, Thornley JP et al. Increased rectal mucosal Hepatol. 2009; 21: 183–9.
enteroendocrine cells, T lymphocytes, and increased gut permeability Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd following acute Campylobacter enteritis and in post-dysenteric citalopram does not affect colonic sensitivity or compliance in rats.
irritable bowel syndrome. Gut 2000; 47: 804–11.
Eur. J. Pharmacol. 2007; 570: 203–11.
35 Lee V, Guthrie E, Robinson A et al. Functional bowel disorders in 54 Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, primary care: factors associated with health-related quality of life Janssens J. A controlled crossover study of the selective serotonin and doctor consultation. J. Psychosom. Res. 2008; 64: 129–38.
reuptake inhibitor citalopram in irritable bowel syndrome. Gut 2006; 36 Dhaliwal SK, Hunt RH. Doctor-patient interaction for irritable bowel 55: 1095–103.
syndrome in primary care: a systematic perspective. Eur. J. 55 Rahimi R, Nikfar S, Rezaie A, Abdollahi M. Efficacy of tricyclic Gastroenterol. Hepatol. 2004; 16: 1161–6.
antidepressants in irritable bowel syndrome: a meta-analysis. World 37 Rosen SD, Paulesu E, Nihoyannopoulos P et al. Silent ischemia J. Gastroenterol. 2009; 15: 1548–53.
as a central problem: regional brain activation compared in silent 56 Callahan MJ. Irritable bowel syndrome neuropharmacology. A and painful myocardial ischemia. Ann. Intern. Med. 1996; 124:
review of approved and investigational compounds. J. Clin. Gastroenterol. 2002; 35 (1 Suppl.): S58–67.
38 Kern MK, Shaker R. Cerebral cortical registration of subliminal 57 Thompson CA. Novartis suspends tegaserod sales at FDA’s request.
visceral stimulation. Gastroenterology 2002; 122: 290–8.
Am. J. Health Syst. Pharm. 2007; 64: 1020.
39 Gershon MD. Nerves, reflexes, and the enteric nervous system: 58 Sweetser S, Busciglio IA, Camilleri M et al. Effect of a chloride pathogenesis of the irritable bowel syndrome. J. Clin. Gastroenterol. channel activator, lubiprostone, on colonic sensory and motor 2005; 39 (5 Suppl. 3): S184–193.
functions in healthy subjects. Am. J. Physiol. Gastrointest. Liver 40 Brehmer A, Croner R, Dimmler A, Papadopoulos T, Schrodl F, Physiol. 2009; 296: G295–301.
Neuhuber W. Immunohistochemical characterization of putative 59 Lang L. The Food and Drug Administration approves lubiprostone primary afferent (sensory) myenteric neurons in human small for irritable bowel syndrome with constipation. Gastroenterology intestine. Auton. Neurosci. 2004; 112: 49–59.
2008; 135: 7.
41 Nagakura Y, Kontoh A, Tokita K, Tomoi M, Shimomura K, 60 Ford AC, Talley NJ, Spiegel BM et al. Effect of fibre, Kadowaki M. Combined blockade of 5-HT3- and 5-HT4-serotonin antispasmodics, and peppermint oil in the treatment of irritable receptors inhibits colonic functions in conscious rats and mice. J. bowel syndrome: systematic review and meta-analysis. BMJ 2008; Pharmacol. Exp. Ther. 1997; 281: 284–90.
337: a2313.
42 Mazzia C, Hicks GA, Clerc N. Neuronal location of 61 Hanauer SB. The benefits of loperamide in the treatment of patients 5-hydroxytryptamine3 receptor-like immunoreactivity in the rat with IBS or IBD. Introduction. Rev. Gastroenterol. Disord. 2007; 7
colon. Neuroscience 2003; 116: 1033–41.
43 Taniyama K, Makimoto N, Furuichi A et al. Functions of peripheral 62 Palmer KR, Corbett CL, Holdsworth CD. Double-blind cross-over 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine4 study comparing loperamide, codeine and diphenoxylate in the receptor, in gastrointestinal motility. J. Gastroenterol. 2000; 35:
treatment of chronic diarrhea. Gastroenterology 1980; 79: 1272–5.
63 Goldberg PA, Kamm MA, Setti-Carraro P, Van Der Sijp JR, Roth C.
44 Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD.
Modification of visceral sensitivity and pain in irritable bowel Localization and function of a 5-HT transporter in crypt epithelia of syndrome by 5-HT3 antagonism (ondansetron). Digestion 1996; 57:
the gastrointestinal tract. J. Neurosci. 1996; 16: 2352–64.
45 Coates MD, Mahoney CR, Linden DR et al. Molecular defects in 64 Milne RJ, Heel RC. Ondansetron. Therapeutic use as an antiemetic.
mucosal serotonin content and decreased serotonin reuptake Drugs 1991; 41: 574–95.
transporter in ulcerative colitis and irritable bowel syndrome.
65 Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Gastroenterology 2004; 126: 1657–64.
alosetron for the treatment of irritable bowel syndrome in women 46 Hoveyda N, Heneghan C, Mahtani KR, Perera R, Roberts N, and men: a meta-analysis of eight randomized, placebo-controlled, Glasziou P. A systematic review and meta-analysis: probiotics in the 12-week trials. Clin. Ther. 2008; 30: 884–901.
treatment of irritable bowel syndrome. BMC Gastroenterol. 2009; 9:
66 Fayyaz M, Lackner JM. Serotonin receptor modulators in the treatment of irritable bowel syndrome. Ther. Clin. Risk Manag. 2008; 47 Burden S. Dietary treatment of irritable bowel syndrome: current 4: 41–8.
evidence and guidelines for future practice. J. Hum. Nutr. Diet. 2001; 67 Kobayashi S, Ikeda K, Suzuki M, Yamada T, Miyata K. Effects of 14: 231–41.
YM905, a novel muscarinic M3-receptor antagonist, on experimental 48 McFarland LV, Dublin S. Meta-analysis of probiotics for the models of bowel dysfunction in vivo. Jpn. J. Pharmacol. 2001; 86:
treatment of irritable bowel syndrome. World J. Gastroenterol. 2008; 14: 2650–61.
68 Wallis RM. Pre-clinical and clinical pharmacology of selective 49 Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P.
muscarinic M3 receptor antagonists. Life Sci. 1995; 56: 861–8.
Efficacy of antidepressants and psychological therapies in irritable 69 Bradesi S, Herman J, Mayer EA. Visceral analgesics: drugs with a bowel syndrome: systematic review and meta-analysis. Gut 2009; 58:
great potential in functional disorders? Curr. Opin. Pharmacol. 2008; 8: 697–703.
50 Jackson JL, O’Malley PG, Tomkins G, Balden E, Santoro J, 70 Liu JP, Yang M, Liu YX, Wei ML, Grimsgaard S. Herbal medicines Kroenke K. Treatment of functional gastrointestinal disorders with for treatment of irritable bowel syndrome. Cochrane Database Syst. antidepressant medications: a meta-analysis. Am. J. Med. 2000; 108:
Rev. 2006; 1: CD004116.
71 Bensoussan A, Talley NJ, Hing M, Menzies R, Guo A, Ngu M.
51 Lydiard RB, Falsetti SA. Experience with anxiety and depression Treatment of irritable bowel syndrome with Chinese herbal treatment studies: implications for designing irritable bowel medicine: a randomized controlled trial. JAMA 1998; 280: 1585–9.
syndrome clinical trials. Am. J. Med. 1999; 107 (5A): 65S–73S.
72 Madisch A, Holtmann G, Plein K, Hotz J. Treatment of irritable 52 Halpert A, Dalton CB, Diamant NE et al. Clinical response to bowel syndrome with herbal preparations: results of a double-blind, tricyclic antidepressants in functional bowel disorders is not related randomized, placebo-controlled, multi-centre trial. Aliment. to dosage. Am. J. Gastroenterol. 2005; 100: 664–71.
Pharmacol. Ther. 2004; 19: 271–9.
53 Kall E, Lindstrom E, Martinez V. The serotonin reuptake inhibitor 73 Sallon S, Ben-Arye E, Davidson R, Shapiro H, Ginsberg G, Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Ligumsky M. A novel treatment for constipation-predominant channel dependent processes in intestinal, neuronal and cardiac irritable bowel syndrome using Padma Lax, a Tibetan herbal preparations. Aliment. Pharmacol. Ther. 1988; 2: 101–18.
formula. Digestion 2002; 65: 161–71.
77 Micklefield G, Jung O, Greving I, May B. Effects of intraduodenal 74 Krueger D, Gruber L, Buhner S et al. The multi-herbal drug STW 5 application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) (Iberogast(R)) has prosecretory action in the human intestine.
1520) on gastroduodenal motility in healthy volunteers. Phytother. Neurogastroenterol. Motil. 2009; 21: 1203–e110.
Res. 2003; 17: 135–40.
75 Shen YH, Nahas R. Complementary and alternative medicine for 78 Lim B, Manheimer E, Lao L et al. Acupuncture for treatment of treatment of irritable bowel syndrome. Can. Fam. Physician 2009; irritable bowel syndrome. Cochrane Database Syst. Rev. 2006; 4:
55: 143–8.
76 Hawthorn M, Ferrante J, Luchowski E, Rutledge A, Wei XY, 79 Bradesi S, Mayer EA. Novel therapeutic approaches in IBS. Curr. Triggle DJ. The actions of peppermint oil and menthol on calcium Opin. Pharmacol. 2007; 7: 598–604.
Journal of Gastroenterology and Hepatology 25 (2010) 691–699
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Copyright of Journal of Gastroenterology & Hepatology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.


III Seminário de Pesquisa Interdisciplinar A primeira década novo milênio: sociedade, instituições e inovações Universidade do Sul de Santa Catarina, SC, Brasil, 9, 10 e 11 de maio de 2011 A PROTEÇÃO JURIDICA DOS DIREITOS DE PROPRIEDADE INDUSTRIAL AO DEPOSITANTE DO PEDIDO DA CARTA-PATENTE E DO REGISTRO DE MARCA, PENDENTE O PRAZO DE ANÁLISE JUNTO AO INSTITUTO NACI

Microsoft word - logo from showgo

EMS Protocols INTRODUCTION The following protocols have been written to unify and simplify the roles of the various levels of EMS personnel in the field. The format has been written to provide historical information, as well as step-wise care instructions. The EMS provider is expected to be responsible for all the steps in the delivery of care up to the level of training they hold. Fo

Copyright © 2011-2018 Health Abstracts