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Irritable Bowel Syndrome: Modern Concepts and Management Options

  • Gregory S. Sayuk
    Affiliations
    Division of Gastroenterology, Washington University School of Medicine, St Louis, Mo

    Department of Psychiatry, Washington University School of Medicine, St Louis, Mo

    John Cochran Veteran Affairs Medical Center, St Louis, Mo
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  • C. Prakash Gyawali
    Correspondence
    Requests for reprints should be addressed to C. Prakash Gyawali, MD, Division of Gastroenterology, Campus Box 8124, 660 S. Euclid Ave, St Louis, MO 63124.
    Affiliations
    Division of Gastroenterology, Washington University School of Medicine, St Louis, Mo
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Published:February 28, 2015DOI:https://doi.org/10.1016/j.amjmed.2015.01.036

      Abstract

      Irritable bowel syndrome is the most common functional gastrointestinal disorder, manifesting as abdominal pain/discomfort and altered bowel function. Despite affecting as many as 20% of adults, a lack of understanding of etiopathogenesis and evaluation strategies results in diagnostic uncertainty, and in turn frustration of both the physician and the patient. This review summarizes the current literature on the diagnosis and management of irritable bowel syndrome, with attention to evidence-based approaches. A 4-step treatment strategy that has been used successfully in our tertiary referral practice is presented and should lead to successful therapeutic outcomes in the majority of patients with irritable bowel syndrome.

      Keywords

      Clinical Significance
      • Advances in the understanding of irritable bowel syndrome pathophysiology have been made in recent years.
      • These insights inform a treatment strategy for the management of irritable bowel syndrome.
      • The implementation of this approach will yield favorable treatment outcomes in the majority of patients with irritable bowel syndrome.
      The functional gastrointestinal disorders represent chronic gastrointestinal conditions with altered bowel sensitivity and motility.
      Irritable bowel syndrome is the most common functional gastrointestinal disorder, manifesting as abdominal pain/discomfort and altered bowel function.
      • Longstreth G.F.
      • Thompson W.G.
      • Chey W.D.
      • et al.
      Functional bowel disorders.

      Demographics, Disease Burden, and Clinical Presentation

      Irritable bowel syndrome has a prevalence of 1% to 20% worldwide, although up to 75% affected individuals never seek care.
      • Drossman D.A.
      • Li Z.
      • Andruzzi E.
      • et al.
      U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact.
      • El-Serag H.B.
      Impact of irritable bowel syndrome: prevalence and effect on health-related quality of life.
      • Hungin A.
      • Chang L.
      • Locke G.
      • et al.
      Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact.
      • Longstreth G.F.
      • Wolde-Tsadik G.
      Irritable bowel-type symptoms in HMO examinees. Prevalence, demographics, and clinical correlates.
      In North America, irritable bowel syndrome prevalence is 5% to 10%, affecting any age, and is 3 to 4 times more common in women. Irritable bowel syndrome health-related quality of life is similar to that of those with asthma and worse than that of those with chronic liver disease.
      • Gralnek I.M.
      • Hays R.D.
      • Kilbourne A.
      • et al.
      The impact of irritable bowel syndrome on health-related quality of life.
      • Wyrwich K.W.
      • Nelson H.S.
      • Tierney W.M.
      • et al.
      Clinically important differences in health-related quality of life for patients with asthma: an expert consensus panel report.
      • Younossi Z.M.
      • Boparai N.
      • Price L.L.
      • et al.
      Health-related quality of life in chronic liver disease: the impact of type and severity of disease.
      Irritable bowel syndrome leads to $1.6 billion in direct medical costs and $19 billion in indirect costs annually.
      • Longstreth G.F.
      • Wilson A.
      • Knight K.
      • et al.
      Irritable bowel syndrome, health care use, and costs: a U.S. managed care perspective.
      • Nyrop K.A.
      • Palsson O.S.
      • Levy R.L.
      • et al.
      Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain.
      • Drossman D.A.
      • Camilleri M.
      • Mayer E.A.
      • Whitehead W.E.
      AGA technical review on irritable bowel syndrome.
      Diagnostic criteria for irritable bowel syndrome have been proposed, including the Manning
      • Manning A.P.
      • Thompson W.G.
      • Heaton K.W.
      • Morris A.F.
      Towards positive diagnosis of the irritable bowel.
      and Rome criteria (most recently Rome III, Table 1).
      These criteria, intended primarily as irritable bowel syndrome research tools, have sensitivities of 62% to 96%.
      • Ford A.C.
      • Bercik P.
      • Morgan D.G.
      • et al.
      Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care.
      Although irritable bowel syndrome diagnostic criteria perform variably across studies,
      • Jellema P.
      • van der Windt D.A.
      • Schellevis F.G.
      • van der Horst H.E.
      Systematic review: accuracy of symptom-based criteria for diagnosis of irritable bowel syndrome in primary care.
      • Whitehead W.E.
      • Palsson O.S.
      • Feld A.D.
      • et al.
      Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome.
      they are more robust (95% positive predictive value in one study) in the absence of red flag symptoms.
      • Vanner S.J.
      • Depew W.T.
      • Paterson W.G.
      • et al.
      Predictive value of the Rome criteria for diagnosing the irritable bowel syndrome.
      Irritable bowel syndrome can be further categorized into constipation-predominant, diarrhea-predominant, or mixed patterns (Table 2).
      • Longstreth G.F.
      • Thompson W.G.
      • Chey W.D.
      • et al.
      Functional bowel disorders.
      Organic causes for symptoms must be excluded, especially in older populations. Alarm features prompting further investigation include weight loss, fever, hematochezia, older age, and family history of gastrointestinal malignancy.
      • Whitehead W.E.
      • Palsson O.S.
      • Feld A.D.
      • et al.
      Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome.
      On physical examination, peritoneal signs, ascites, masses, and hemoccult positive stool also constitute alarm signs.
      • Kruis W.
      • Thieme C.
      • Weinzierl M.
      • et al.
      A diagnostic score for the irritable bowel syndrome. Its value in the exclusion of organic disease.
      Table 1Diagnostic Criteria
      Criteria fulfilled for the last 3 mo with symptom onset at least 6 mo before diagnosis.
      for Irritable Bowel Syndrome
      Recurrent abdominal pain or discomfort
      Discomfort means an uncomfortable sensation not described as pain. In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 d/wk during screening evaluation for subject eligibility.
      at least 3 d/mo in the last 3 mo associated with ≥2 of the following:
      • 1.
        Improvement with defecation
      • 2.
        Onset associated with a change in frequency of stool
      • 3.
        Onset associated with a change in form (appearance) of stool
      Supporting symptoms (not required for diagnosis but helpful in confirming IBS presentation): a) abnormal stool frequency (<3 bowel movements per week or >3 bowel movements per day); b) abnormal stool form; c) defecation straining; d) urgency (feeling of incomplete evacuation); e) passage of mucus; f) bloating
      IBS = irritable bowel syndrome.
      Criteria fulfilled for the last 3 mo with symptom onset at least 6 mo before diagnosis.
      Discomfort means an uncomfortable sensation not described as pain. In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 d/wk during screening evaluation for subject eligibility.
      Table 2Subtyping Irritable Bowel Syndrome by Predominant Stool Pattern
      • 1.
        IBS with constipation—hard or lumpy stools
        Bristol Stool Form Scale 1-2 (separate hard lumps like nuts [difficult to pass] or sausage-shaped but lumpy).
        ≥25% and loose (mushy) or watery stools
        Bristol Stool Form Scale 6-7 (fluffy pieces with ragged edges, a mushy stool or watery, no solid pieces, entirely liquid).
        ≤25% of bowel movements
        In the absence of use of antidiarrheals or laxatives.
      • 2.
        IBS with diarrhea—loose (mushy) or watery stools
        Bristol Stool Form Scale 6-7 (fluffy pieces with ragged edges, a mushy stool or watery, no solid pieces, entirely liquid).
        ≥25% and hard or lumpy stool
        Bristol Stool Form Scale 1-2 (separate hard lumps like nuts [difficult to pass] or sausage-shaped but lumpy).
        ≤25% of bowel movements
        In the absence of use of antidiarrheals or laxatives.
      • 3.
        Mixed IBS—hard or lumpy stools
        Bristol Stool Form Scale 1-2 (separate hard lumps like nuts [difficult to pass] or sausage-shaped but lumpy).
        ≥25% and loose (mushy) or watery stools
        Bristol Stool Form Scale 6-7 (fluffy pieces with ragged edges, a mushy stool or watery, no solid pieces, entirely liquid).
        ≥25% of bowel movements
        In the absence of use of antidiarrheals or laxatives.
      • 4.
        Unsubtyped IBS—insufficient abnormality of stool consistency to meet criteria for IBS with constipation, diarrhea, or mixed
        In the absence of use of antidiarrheals or laxatives.
      IBS = irritable bowel syndrome.
      Bristol Stool Form Scale 1-2 (separate hard lumps like nuts [difficult to pass] or sausage-shaped but lumpy).
      Bristol Stool Form Scale 6-7 (fluffy pieces with ragged edges, a mushy stool or watery, no solid pieces, entirely liquid).
      In the absence of use of antidiarrheals or laxatives.
      Mood disorders and nongastrointestinal functional pain syndromes (eg, fibromyalgia, migraine) are present in up to two thirds of patients with irritable bowel syndrome,
      • Sayuk G.S.
      • Elwing J.E.
      • Lustman P.J.
      • Clouse R.E.
      High somatic symptom burdens and functional gastrointestinal disorders.
      • Whitehead W.E.
      • Palsson O.S.
      • Levy R.R.
      • et al.
      Comorbidity in irritable bowel syndrome.
      whereas somatization (perceptive symptoms across multiple systems) occurs in 40%.
      • Brown W.H.
      • Chey W.D.
      • Elta G.H.
      Number of responses on a review of systems questionnaire predicts the diagnosis of functional gastrointestinal disorders.
      Multiple medication intolerances or adverse effects frequently are encountered in patients with irritable bowel syndrome.

      Etiopathogenesis

      Both peripheral (gut-based) and central (eg, abnormal brain responses to peripheral bowel signals) pathophysiologic mechanisms play an etiopathogenetic role,
      • Ohman L.
      • Simren M.
      Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions.
      • Mayer E.A.
      • Naliboff B.D.
      • Craig A.D.
      Neuroimaging of the brain-gut axis: from basic understanding to treatment of functional GI disorders.
      although no single mechanism can explain all irritable bowel syndrome cases.
      • Drossman D.A.
      • Camilleri M.
      • Mayer E.A.
      • Whitehead W.E.
      AGA technical review on irritable bowel syndrome.
      Inflammation, infection, gut motility, and brain-gut axis disturbances all partially explain symptom triggering or perpetuation; enhanced visceral sensitivity from upregulation of bowel sensation and greater afferent nerve signaling also participate in irritable bowel syndrome pathogenesis. Sensitization of afferent neural pathways allows physiologic gut stimuli to produce pain or motor symptoms.
      • Mayer E.A.
      • Naliboff B.D.
      • Craig A.D.
      Neuroimaging of the brain-gut axis: from basic understanding to treatment of functional GI disorders.
      • Ladabaum U.
      • Minoshima S.
      • Owyang C.
      Pathobiology of visceral pain: molecular mechanisms and therapeutic implications V. Central nervous system processing of somatic and visceral sensory signals.
      • Hasler W.L.
      Traditional thoughts on the pathophysiology of irritable bowel syndrome.
      Visceral hypersensitivity can be reproduced experimentally using rectal balloon distention in some patients.
      • Chang L.
      • Mayer E.A.
      • Johnson T.
      • et al.
      Differences in somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia.
      As a symptom-based diagnosis, multiple conditions may mimic irritable bowel syndrome. Some of these (ie, celiac disease) are common enough to warrant routine diagnostic testing (see “Diagnostic Strategy”). Less common conditions, such as bile acid diarrhea, microscopic colitis, and pancreatic insufficiency,
      • Leeds J.S.
      • Hopper A.D.
      • Sidhu R.
      • et al.
      Some patients with irritable bowel syndrome may have exocrine pancreatic insufficiency.
      • Money M.E.
      • Camilleri M.
      Review: management of postprandial diarrhea syndrome.
      • Simadibrata M.
      • Wanders R.J.
      • Jan G.
      • et al.
      Examination of small bowel enzymes in chronic diarrhea.
      • Walters J.R.
      Defining primary bile acid diarrhea: making the diagnosis and recognizing the disorder.
      • Bajor A.
      • Tornblom H.
      • Rudling M.
      • et al.
      Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS.
      require a clinical suspicion to invoke the appropriate diagnostic approaches.
      Alterations in gut secretory and motor function can manifest as meal-triggered diarrhea, resulting in rapid small-bowel transit.
      • Deiteren A.
      • Camilleri M.
      • Bharucha A.E.
      • et al.
      Performance characteristics of scintigraphic colon transit measurement in health and irritable bowel syndrome and relationship to bowel functions.
      • Deiteren A.
      • Camilleri M.
      • Burton D.
      • et al.
      Effect of meal ingestion on ileocolonic and colonic transit in health and irritable bowel syndrome.
      Neurotransmitters such as serotonin are key in regulating and modulating intestinal transit, through serotonin type 3 (5-HT3) and 4 (5-HT4) receptors;
      • Gershon M.D.
      • Tack J.
      The serotonin signaling system: from basic understanding to drug development for functional GI disorders.
      treatment strategies targeting serotoninergic receptors have proven effective.
      Intestinal inflammation and the microbiome are emerging factors in irritable bowel syndrome etiopathogenesis.
      • Ohman L.
      • Simren M.
      Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions.
      • Simren M.
      • Barbara G.
      • Flint H.J.
      • et al.
      Intestinal microbiota in functional bowel disorders: a Rome foundation report.
      Although overt small bowel bacterial overgrowth may initiate irritable bowel syndrome symptoms,
      • Ohman L.
      • Simren M.
      Intestinal microbiota and its role in irritable bowel syndrome (IBS).
      lesser degrees of bacterial colonization may be sufficient to produce irritable bowel syndrome-like symptoms.
      • Posserud I.
      • Stotzer P.O.
      • Bjornsson E.S.
      • et al.
      Small intestinal bacterial overgrowth in patients with irritable bowel syndrome.
      • Jeffery I.B.
      • O'Toole P.W.
      • Ohman L.
      • et al.
      An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota.
      Infectious gastroenteritis may trigger microinflammation (“postinfectious irritable bowel syndrome”), and up to one third of irritable bowel syndrome cases follow acute gastroenteritis
      • Spiller R.
      • Garsed K.
      Postinfectious irritable bowel syndrome.
      ; conversely, only 7% to 30% patients with acute gastroenteritis develop irritable bowel syndrome.
      • Grover M.
      • Camilleri M.
      • Smith K.
      • et al.
      On the fiftieth anniversary postinfectious irritable bowel syndrome: mechanisms related to pathogens.
      Psychologic distress is an important cofactor when persistent functional symptoms follow enteric infection.
      • Gwee K.A.
      • Leong Y.L.
      • Graham C.
      • et al.
      The role of psychological and biological factors in postinfective gut dysfunction.
      • Nielsen H.L.
      • Engberg J.
      • Ejlertsen T.
      • Nielsen H.
      Psychometric scores and persistence of irritable bowel after Campylobacter concisus infection.
      Abnormal brain activation responses to noxious rectal stimulation on functional neuroimaging are present in some irritable bowel syndrome cases.
      • Labus J.S.
      • Naliboff B.D.
      • Berman S.M.
      • et al.
      Brain networks underlying perceptual habituation to repeated aversive visceral stimuli in patients with irritable bowel syndrome.
      • Larsson M.B.
      • Tillisch K.
      • Craig A.D.
      • et al.
      Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome.
      • Mayer E.A.
      • Aziz Q.
      • Coen S.
      • et al.
      Brain imaging approaches to the study of functional GI disorders: a Rome working team report.
      The brain regions implicated (eg, anterior cingulate, insula) also are responsible for affective responses;
      • Mayer E.A.
      • Naliboff B.D.
      • Craig A.D.
      Neuroimaging of the brain-gut axis: from basic understanding to treatment of functional GI disorders.
      these observations offer strong evidence for aberrant brain neurocircuitry in irritable bowel syndrome.
      Many patients with irritable bowel syndrome perceive food to be important symptom triggers;
      • Bohn L.
      • Storsrud S.
      • Tornblom H.
      • et al.
      Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life.
      dietary intolerances, particularly lactose, are present in one third of patients with irritable bowel syndrome.
      • Yang J.
      • Fox M.
      • Cong Y.
      • et al.
      Lactose intolerance in irritable bowel syndrome patients with diarrhoea: the roles of anxiety, activation of the innate mucosal immune system and visceral sensitivity.
      Deficiencies of other disaccharidases (sucrose, maltase) can lead to diarrhea,
      • Simadibrata M.
      • Wanders R.J.
      • Jan G.
      • et al.
      Examination of small bowel enzymes in chronic diarrhea.
      and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols can yield methane, hydrogen, and carbon dioxide production implicated in bloating.
      • Marcason W.
      What is the FODMAP diet?.
      • Muir J.G.
      • Gibson P.R.
      The low FODMAP diet For treatment of irritable bowel syndrome and other gastrointestinal disorders.
      • Staudacher H.M.
      • Irving P.M.
      • Lomer M.C.
      • Whelan K.
      Mechanisms and efficacy of dietary FODMAP restriction in IBS.
      Osmotically active carbohydrate by-products precipitate fluid secretion and enhance intestinal contraction, leading to diarrhea. Evidence for the role of gluten exposure in irritable bowel syndrome is mixed; controlled studies have failed to indict gluten in the absence of celiac disease, whereas other reports suggest contribution to symptoms.
      • Ferch C.C.
      • Chey W.D.
      Irritable bowel syndrome and gluten sensitivity without celiac disease: separating the wheat from the chaff.
      • Vazquez-Roque M.I.
      • Camilleri M.
      • Smyrk T.
      • et al.
      A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function.
      In addition to amplifying visceral pain pathways, psychologic states influence illness and health care-seeking behaviors. Comorbid mood disorders or somatization portend a several-fold higher likelihood of developing functional gastrointestinal disorders
      • Sayuk G.S.
      • Elwing J.E.
      • Lustman P.J.
      • Clouse R.E.
      High somatic symptom burdens and functional gastrointestinal disorders.
      with more severe symptoms, lower health-related quality of life, and higher treatment refractoriness.
      • Sayuk G.S.
      • Elwing J.E.
      • Lustman P.J.
      • Clouse R.E.
      Predictors of premature antidepressant discontinuation in functional gastrointestinal disorders.
      • North C.S.
      • Hong B.A.
      • Alpers D.H.
      Relationship of functional gastrointestinal disorders and psychiatric disorders: implications for treatment.
      • Spiegel B.M.
      • Gralnek I.M.
      • Bolus R.
      • et al.
      Clinical determinants of health-related quality of life in patients with irritable bowel syndrome.
      Finally, convincing evidence exists for a genetic basis to irritable bowel syndrome; despite this, no single genetic defect reliably accounts for all cases. Genetic polymorphisms predict endophenotypes, such as inflammatory and infectious triggering, symptom burden, and visceral hypersensitivity.
      • Saito Y.A.
      • Talley N.J.
      Genetics of irritable bowel syndrome.
      • Saito Y.A.
      • Zimmerman J.M.
      • Harmsen W.S.
      • et al.
      Irritable bowel syndrome aggregates strongly in families: a family-based case-control study.
      Gene–gene interactions and environmental influences probably are key to genetic predispositions.
      • Camilleri M.
      • Katzka D.A.
      Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome.
      • Ek W.E.
      • Reznichenko A.
      • Ripke S.
      • et al.
      Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts.
      Figure 1 illustrates the complex interplay of environmental, psychologic, and physiologic factors in irritable bowel syndrome pathophysiology via a biopsychosocial model.
      • Bradford K.
      • Shih W.
      • Videlock E.J.
      • et al.
      Association between early adverse life events and irritable bowel syndrome.
      • Chang L.
      The role of stress on physiologic responses and clinical symptoms in irritable bowel syndrome.
      Figure thumbnail gr1
      Figure 1A biopsychosocial model of irritable bowel syndrome pathophysiology. Irritable bowel syndrome is thought to be a multifactorial disorder, deriving from a potential multitude of etiopathogenic factors, including environmental, psychologic, and physiologic factors. This model highlights the complex, often bidirectional interplay of these factors in the experience of irritable bowel syndrome symptoms. cGMP = cyclic guanosine monophosphate; 5-HT3 = serotonin type 3; 5-HT4 = serotonin type 4; FODMAPS = fermentable oligosaccharides, disaccharides, monosaccharides, and polyols; HRQOL = health-related quality of life; IBS = irritable bowel syndrome.

      Diagnostic Strategy

      Laboratory and invasive testing are minimized, because repetitive investigations are costly and reinforce illness behavior. History alone without alarm symptoms yields likelihood ratios of 3 to 5 favoring irritable bowel syndrome.
      • Ford A.C.
      • Bercik P.
      • Morgan D.G.
      • et al.
      Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care.
      • Ford A.C.
      • Talley N.J.
      • Veldhuyzen van Zanten S.J.
      • et al.
      Will the history and physical examination help establish that irritable bowel syndrome is causing this patient's lower gastrointestinal tract symptoms?.
      Complete blood counts, erythrocyte sedimentation rate, and fecal occult blood tests may be appropriate early in evaluation. A bland physical examination (abdomen without peritoneal signs or palpable masses; no concerning extra-abdominal findings), a consistent history, and normal laboratory results yield robust post-test probability of irritable bowel syndrome.
      • Kruis W.
      • Thieme C.
      • Weinzierl M.
      • et al.
      A diagnostic score for the irritable bowel syndrome. Its value in the exclusion of organic disease.
      The history should gauge any temporal association with medications or food as symptom triggers, recent changes in anatomy (gastric or intestinal surgery, cholecystectomy), exposures (travel, children), or gastrointestinal infections (enteritis, Clostridium difficile). With a 4% overlap between celiac disease and irritable bowel syndrome, celiac testing is a cost-effective strategy.
      • Ford A.C.
      • Chey W.D.
      • Talley N.J.
      • et al.
      Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis.
      • Spiegel B.M.
      • DeRosa V.P.
      • Gralnek I.M.
      • et al.
      Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analysis.
      Hydrogen breath tests for bacterial overgrowth (∼50%) are inadequate to predict responses to antibiotics
      • Ford A.C.
      • Spiegel B.M.
      • Talley N.J.
      • Moayyedi P.
      Small intestinal bacterial overgrowth in irritable bowel syndrome: systematic review and meta-analysis.
      • Fumi A.L.
      • Trexler K.
      Rifaximin treatment for symptoms of irritable bowel syndrome.
      ; therefore, empiric antibiotics may be a more cost-effective strategy when used judiciously. Testing for carbohydrate intolerance should be reserved for ambiguous cases or when further education and dietary monitoring may enhance symptom control.
      • American College of Gastroenterology Task Force on Irritable Bowel
      • Brandt L.J.
      • Chey W.D.
      • Foxx-Orenstein A.E.
      • et al.
      An evidence-based position statement on the management of irritable bowel syndrome.
      Colonoscopy is considered in patients aged more than 50 years as part of routine colon cancer screening and in patients with alarm features.
      • Spiller R.
      • Aziz Q.
      • Creed F.
      • et al.
      Guidelines on the irritable bowel syndrome: mechanisms and practical management.
      Melanosis coli indicating laxative use and microinflammatory disease can be identified during colonoscopy. Endoscopy is unnecessary in young patients with classic irritable bowel syndrome symptoms.
      • Chey W.D.
      • Nojkov B.
      • Rubenstein J.H.
      • et al.
      The yield of colonoscopy in patients with non-constipated irritable bowel syndrome: results from a prospective, controlled US trial.

      Irritable Bowel Syndrome Treatment

      This section will offer guidance on the treatment of irritable bowel syndrome, emphasizing an evidence-based approach where available. First, an overview of the available treatment options will be offered; subsequently, we suggest a 4-step treatment approach to irritable bowel syndrome management. The proposed implementation strategy has not been studied systematically, but has proven successful in our tertiary gastrointestinal practice composed largely of patients with severe, treatment-refractory irritable bowel syndrome. Similar strategies have been endorsed by other experts in the field.
      • Drossman D.A.
      • Chang L.
      • Bellamy N.
      • et al.
      Severity in irritable bowel syndrome: a Rome Foundation Working Team report.

      Overview of Irritable Bowel Syndrome Treatment Options

      After the exclusion of disorders mimicking irritable bowel syndrome and elimination of potential symptom triggers, the cornerstone of irritable bowel syndrome management is pharmacotherapy using peripherally and centrally acting agents (Table 3). Peripherally acting agents target dominant symptoms, whereas centrally acting agents act “globally,” improving pain and well-being.
      Table 3Therapeutic Approaches to Managing Irritable Bowel Syndrome
      All PatientsGut Luminal and Mucosal TherapiesGut-Directed RegulatorsCentrally Acting AgentsAdjunctive and Complementary Therapy
      Step 1Step 2Step 3Step 4
      ReassuranceDietary modification (low FODMAP, lactose)Guanylate cyclase C agents (linaclotide)Tricyclic antidepressants (amitriptyline, nortriptyline)Psychodynamic therapy
      Limited investigationOsmotic laxatives (PEG, lactulose, magnesium products)Chloride channel activators (lubiprostone)SNRI antidepressants (venlafaxine, desvenlafaxine, duloxetine)Hypnosis
      Patient-doctor relationshipAntidiarrheals (loperamide, diphenoxylate/atropine)

      Bile binders (cholestyramine, colesevelam)
      Serotonin modulators (alosetron)

      Antibiotics (rifaximin, neomycin)
      SSRI antidepressants (citalopram, paroxetine, sertraline)Stress reduction
      Other supportive careAnticholinergics/antispasmodics (methscopolamine, glycopyrrolate, hyoscyamine, dicyclomine)Other centrally acting agents (eg, gabapentin, pregabalin, antiseizure agents)Psychiatrist consultation
      ProbioticsPsychotherapy
      DisaccharidasesAcupuncture
      Herbal therapies?
      FODMAP = fermentable oligosaccharides, disaccharides, monosaccharides, and polyols; PEG = polyethylene glycol; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitors.

      Peripherally Acting Agents

      Constipation-predominant Irritable Bowel Syndrome

      Dietary fiber, both natural (eg, psyllium) and synthetic (eg, methylcellulose), is a simple, inexpensive option in patients with mildly constipated irritable bowel syndrome, with randomized controlled data supporting global symptom relief despite lack of superiority over placebo in meta-analysis.
      • Ruepert L.
      • Quartero A.O.
      • de Wit N.J.
      • et al.
      Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.
      • Moayyedi P.
      • Quigley E.M.
      • Lacy B.E.
      • et al.
      The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis.
      However, fiber potentially worsens bloating. Simple osmotic laxatives (milk of magnesia, polyethylene glycol) are readily available over the counter. Polyethylene glycol improves bowel frequency, but not abdominal pain.
      • Shearer J.
      • Ford A.C.
      Polyethylene glycol in constipation-predominant irritable bowel syndrome.
      • Chapman R.W.
      • Stanghellini V.
      • Geraint M.
      • Halphen M.
      Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome.
      Lactulose and sorbitol have not been studied systematically in irritable bowel syndrome but are effective laxatives; bloating is a side effect, precluding use when this is a prominent symptom.
      • American College of Gastroenterology Task Force on Irritable Bowel
      • Brandt L.J.
      • Chey W.D.
      • Foxx-Orenstein A.E.
      • et al.
      An evidence-based position statement on the management of irritable bowel syndrome.
      Although approved only for “occasional constipation,” osmotic agents generally are safe for long-term use and preferable to stimulant laxatives.
      Tegaserod (Zelnorm, Novartis, Basel, Switzerland) is a partial 5-HT4 receptor agonist marketed for short-term treatment of women with constipated irritable bowel syndrome.
      • Patel S.
      • Berrada D.
      • Lembo A.
      Review of tegaserod in the treatment of irritable bowel syndrome.
      However, it was withdrawn from use due to cardiovascular risk.

      Zelmac (tegaserod) Advisory Committee Briefing Document. Available at: www.fda.gov/ohrms/dockets/ac/00/backgrd/3627b1a.pdf. Accessed February 3, 2014.

      A related agent, prucalopride, is available in several countries, but not in the United States.
      • Quigley E.M.
      Prucalopride: safety, efficacy and potential applications.
      Lubiprostone, a chloride channel type-2 activator, is a prostaglandin-E1 derivative that triggers intestinal chloride secretion, followed by obligatory sodium and fluid transit into the lumen. Lubiprostone is approved for irritable bowel syndrome with constipation, improving bowel movement frequency and global irritable bowel syndrome symptoms.
      • Drossman D.A.
      • Chey W.D.
      • Johanson J.F.
      • et al.
      Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome–results of two randomized, placebo-controlled studies.
      Potential side effects include nausea, diarrhea, and headache. Patients with chronic liver disease may need dose reduction to a single daily dose.

      Amitiza Prescribing Information. Available at: www.amitiza.com. Accessed February 4, 2014.

      Linaclotide is a novel guanylate-cyclase C agonist that upregulates secretion of chloride, followed by sodium and fluid into the bowel lumen; it has been approved for constipation-predominant irritable bowel syndrome.
      • Busby R.W.
      • Kessler M.M.
      • Bartolini W.P.
      • et al.
      Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.
      • Vazquez-Roque M.I.
      • Bouras E.P.
      Linaclotide, novel therapy for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndrome.
      In 2 parallel clinical trials, linaclotide successfully improved bowel movement frequency and irritable bowel syndrome pain.
      • Chey W.D.
      • Lembo A.J.
      • Lavins B.J.
      • et al.
      Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety.
      • Rao S.
      • Lembo A.J.
      • Shiff S.J.
      • et al.
      A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation.
      Increases in cyclic guanosine monophosphate reportedly have direct antinociceptive effects on visceral sensory nerve fibers.
      • Castro J.
      • Harrington A.M.
      • Hughes P.A.
      • et al.
      Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3′,5′-monophosphate.
      Diarrhea is experienced by 20% treated with higher doses of linaclotide (290 μg); this diminishes with continued use; our anecdotal experience suggests lesser diarrhea if administered with meals, despite manufacturer recommendations for administration before meals. Linaclotide is not absorbed and thus has negligible concern for drug interactions or serious systemic side effects.
      • Busby R.W.
      • Kessler M.M.
      • Bartolini W.P.
      • et al.
      Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.
      • Atluri D.K.
      • Chandar A.K.
      • Bharucha A.E.
      • Falck-Ytter Y.
      Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis.

      Diarrhea-predominant Irritable Bowel Syndrome

      The only antidiarrheal agent with randomized, controlled data supporting use in irritable bowel syndrome with diarrhea is loperamide;
      • Efskind P.S.
      • Bernklev T.
      • Vatn M.H.
      A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome.
      • Hanauer S.B.
      The role of loperamide in gastrointestinal disorders.
      diphenoxylate with atropine is a reasonable alternative.
      • Corazziari E.
      Role of opioid ligands in the irritable bowel syndrome.
      Bile acid sequestrants (cholestyramine, colesevelam) are useful when diarrheal symptoms are triggered by bile acids (eg, post-cholecystectomy diarrhea) or as adjuncts.
      • Camilleri M.
      Advances in understanding of bile acid diarrhea.
      • Wong B.S.
      • Camilleri M.
      • Carlson P.
      • et al.
      Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea.
      • Barkun A.N.
      • Love J.
      • Gould M.
      • et al.
      Bile acid malabsorption in chronic diarrhea: pathophysiology and treatment.
      Anticholinergic agents are useful as needed or preemptively in irritable bowel syndrome with diarrhea and postprandial symptoms, especially abdominal pain, bloating, diarrhea, or urgency; modest benefit is reported over placebo in meta-analysis.
      • Ruepert L.
      • Quartero A.O.
      • de Wit N.J.
      • et al.
      Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.
      Examples include hyoscyamine, dicyclomine, and methscopolamine; the latter 2 have lesser central side effects, albeit at higher cost.
      • Saad R.J.
      Peripherally acting therapies for the treatment of irritable bowel syndrome.
      Alosetron, a selective 5-HT3 receptor antagonist, improves bowel consistency and frequency in diarrhea-predominant irritable bowel syndrome; central reduction in brain activation has been suggested as an adjunct mechanism of action.
      • Nakai A.
      • Diksic M.
      • Kumakura Y.
      • et al.
      The effects of the 5-HT3 antagonist, alosetron, on brain serotonin synthesis in patients with irritable bowel syndrome.
      • Lembo A.J.
      • Olden K.W.
      • Ameen V.Z.
      • et al.
      Effect of alosetron on bowel urgency and global symptoms in women with severe, diarrhea-predominant irritable bowel syndrome: analysis of two controlled trials.
      • Mayer E.A.
      • Berman S.
      • Derbyshire S.W.
      • et al.
      The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients.
      • Lembo T.
      • Wright R.A.
      • Bagby B.
      • et al.
      Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome.
      Alosetron was voluntarily withdrawn by the manufacturer because of the risk of acute ischemic colitis, but it was reapproved for chronic, severe diarrhea-predominant irritable bowel syndrome refractory to conventional therapy; currently, its use requires patient agreement and prescriber registration.
      • Andresen V.
      • Hollerbach S.
      Reassessing the benefits and risks of alosetron: what is its place in the treatment of irritable bowel syndrome?.
      • Lewis J.H.
      Alosetron for severe diarrhea-predominant irritable bowel syndrome: safety and efficacy in perspective.
      • Shen B.
      • Soffer E.E.
      Alosetron (Lotronex) is back: should I use it to treat my patients with irritable bowel syndrome?.
      Bile sequestrant therapy is an effective option in patients with diarrheal irritable bowel syndrome, in particular when bile acid malabsorption can be established (SeHCAT scanning, available in specialized settings; abnormal in 1% to 10% of patients with diarrheal irritable bowel syndrome).
      • Deiteren A.
      • Camilleri M.
      • Bharucha A.E.
      • et al.
      Performance characteristics of scintigraphic colon transit measurement in health and irritable bowel syndrome and relationship to bowel functions.
      • Wedlake L.
      • A'Hern R.
      • Russell D.
      • et al.
      Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome.
      In a systematic review, 96% of patients with severe bile acid malabsorption responded well to cholestyramine.
      • Wedlake L.
      • A'Hern R.
      • Russell D.
      • et al.
      Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome.
      However, this medication is not particularly palatable. Colesevelam is a less well-studied and more expensive option for bile acid malabsorption. In patients in whom carbohydrate intolerance is suspected in the setting of postprandial provocation of symptoms, the initiation of disaccharidase therapy (eg, lactase, alpha-amylase) with meals may be both therapeutic and diagnostic.
      • Walters J.R.
      Defining primary bile acid diarrhea: making the diagnosis and recognizing the disorder.

      Centrally Acting Agents

      Antidepressants are beneficial in refractory irritable bowel syndrome independently of their effect on comorbid affective disorders
      • Clouse R.E.
      • Prakash C.
      • Anderson R.J.
      Antidepressants for functional gastrointestinal symptoms and syndromes: a meta-analysis.
      via modulation of brain interpretation of peripheral gut signaling.
      • Clouse R.E.
      Antidepressants for irritable bowel syndrome.
      • Morgan V.
      • Pickens D.
      • Gautam S.
      • et al.
      Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome.
      Tricyclic antidepressants (nortriptyline, amitriptyline) are the best studied antidepressants for irritable bowel syndrome; used in low doses (starting dose 10-25 mg at bedtime), they have negligible mood effects. Clinical trials have demonstrated benefit of tricyclic agents regardless of irritable bowel syndrome subtype; these medications may take weeks and several dose titrations to maximize efficacy.
      • Ruepert L.
      • Quartero A.O.
      • de Wit N.J.
      • et al.
      Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.
      • Ford A.C.
      • Quigley E.M.
      • Lacy B.E.
      • et al.
      Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis.
      The anticholinergic properties of tricyclics slow bowel transit and relieve spasm, but may be responsible for side effects (dry mouth, urinary retention); other side effects include sedation and sexual dysfunction. Switching to secondary amines (eg, despiramine) may mitigate these effects.
      • Clouse R.E.
      Antidepressants for irritable bowel syndrome.
      Selective serotonin reuptake inhibitors are nearly as effective as tricyclics, with a number needed to treat of 3.5 in meta-analysis.
      • Ford A.C.
      • Talley N.J.
      • Schoenfeld P.S.
      • et al.
      Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis.
      Specific agents' properties may benefit particular clinical settings; for instance, citalopram has effects on colonic tone and sensitivity, and paroxetine has anticholinergic effect useful in diarrhea. In contrast to tricyclics, selective serotonergic agents benefit comorbid affective disorders. Serotonin norepinephrine reuptake inhibitors (eg, venlafaxine) are alternative centrally acting agents, with greater pain suppression than serotonin reuptake inhibitors. Venlafaxine also has peripheral effects, inducing colonic relaxation in healthy volunteers.
      • Grover M.
      • Camilleri M.
      Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases.

      Antibiotics and Probiotics

      Gut-specific antibiotics (eg, rifaximin, neomycin) are options when small bowel bacterial overgrowth is suspected, particularly with gas and bloat symptoms. Two large randomized, controlled studies demonstrated global benefit with rifaximin in nonconstipated irritable bowel syndrome (number needed to treat ∼11),
      • Menees S.B.
      • Maneerattannaporn M.
      • Kim H.M.
      • Chey W.D.
      The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis.
      • Pimentel M.
      • Lembo A.
      • Chey W.D.
      • et al.
      Rifaximin therapy for patients with irritable bowel syndrome without constipation.
      and the effect persisted beyond the duration of use.
      • Weinstock L.B.
      Long-term outcome of rifaximin therapy in non-constipation irritable bowel syndrome.
      Emerging data similarly support probiotics, especially Bifidobacteria, Lactobacillus, and Saccharomyces species.
      • Whelan K.
      Probiotics and prebiotics in the management of irritable bowel syndrome: a review of recent clinical trials and systematic reviews.
      • Parkes G.C.
      • Brostoff J.
      • Whelan K.
      • Sanderson J.D.
      Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment.
      Although all probiotics likely are not equal in effectiveness, head-to-head comparisons are lacking.

      Cognitive and Behavioral Therapies

      Psychologic therapies (cognitive behavioral therapy, psychodynamic therapy) show irritable bowel syndrome benefit in global well-being (number needed to treat of 2-4).
      • Ford A.C.
      • Talley N.J.
      • Schoenfeld P.S.
      • et al.
      Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis.
      High patient motivation, pain-predominant symptoms, psychiatric symptoms, and stress triggers predict good responses. Self-directed
      • Lackner J.M.
      • Jaccard J.
      • Krasner S.S.
      • et al.
      Self-administered cognitive behavior therapy for moderate to severe irritable bowel syndrome: clinical efficacy, tolerability, feasibility.
      and internet-based cognitive behavioral therapy
      • Andersson E.
      • Ljotsson B.
      • Smit F.
      • et al.
      Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial.
      • Lindfors P.
      • Ljotsson B.
      • Bjornsson E.
      • et al.
      Patient satisfaction after gut-directed hypnotherapy in irritable bowel syndrome.
      • Ljotsson B.
      • Hedman E.
      • Andersson E.
      • et al.
      Internet-delivered exposure-based treatment vs. stress management for irritable bowel syndrome: a randomized trial.
      offer expanded access, yielding similar yet more cost-effective results.

      Complementary and Alternative Approaches

      Patients with irritable bowel syndrome frequently seek out complementary and alternative strategies.
      • Boyce P.M.
      • Talley N.J.
      • Balaam B.
      • et al.
      A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome.
      • Harris L.R.
      • Roberts L.
      Treatments for irritable bowel syndrome: patients' attitudes and acceptability.
      Hypnotherapy has documented efficacy,
      • Webb A.N.
      • Kukuruzovic R.H.
      • Catto-Smith A.G.
      • Sawyer S.M.
      Hypnotherapy for treatment of irritable bowel syndrome.
      with durable symptom response and reduced health care use, and can be delivered effectively with minimal training.
      • Lindfors P.
      • Unge P.
      • Arvidsson P.
      • et al.
      Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.
      • Palsson O.S.
      • Whitehead W.E.
      Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist.
      • Lindfors P.
      • Unge P.
      • Nyhlin H.
      • et al.
      Long-term effects of hypnotherapy in patients with refractory irritable bowel syndrome.
      Although acupuncture anecdotally provides symptomatic relief, irritable bowel syndrome severity and quality of life are not affected in well-controlled trials.
      • Ford A.C.
      Acupuncture for irritable bowel syndrome.
      • Manheimer E.
      • Wieland L.S.
      • Cheng K.
      • et al.
      Acupuncture for irritable bowel syndrome: systematic review and meta-analysis.
      Among herbal and homeopathic treatments, randomized controlled studies support the use of peppermint oil,
      • Ford A.C.
      • Talley N.J.
      • Spiegel B.M.
      • et al.
      Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis.
      • Rahimi R.
      • Abdollahi M.
      Herbal medicines for the management of irritable bowel syndrome: a comprehensive review.
      iberogast, Padma lax (Padma AG, Schwerzenback, Switzerland), Tong Xie Yao Fang, and Ayurvedic preparations (the latter two are traditional herbalist/pharmacist preparations).
      • Liu J.P.
      • Yang M.
      • Liu Y.X.
      • et al.
      Herbal medicines for treatment of irritable bowel syndrome.
      Purity and consistency concerns limit enthusiasm for these agents. One small trial supports regular exercise in improving irritable bowel syndrome severity scores.
      • Johannesson E.
      • Simren M.
      • Strid H.
      • et al.
      Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial.

      Irritable Bowel Syndrome Treatment: A Four-Step Strategy

      In excluding confounding diagnoses, a limited evaluation is pursued early (see “Diagnostic Strategy”). If irritable bowel syndrome remains likely after evaluation, dietary and affective symptom triggers are considered; other functional disorders, psychiatric comorbidities, and drug intolerances provide corroborative evidence in support of irritable bowel syndrome and inform initial treatment selection.
      Next, a specific treatment approach is selected from the 4 separate, although not necessarily sequential, treatment options (Figure 2). The initial management strategy is determined by 2 factors: symptom severity and dominant symptom (Table 4 and Figure 2).
      Figure thumbnail gr2
      Figure 2Overview of irritable bowel syndrome treatment strategy. Irritable bowel syndrome management involves the use of a continuum of peripheral (gut)-based and centrally acting (brain-gut) strategies. The selection of an appropriate treatment approach for a particular patient with irritable bowel syndrome considers patient severity (eg, effect on daily function/quality of life and overlapping mood disorders) and dominant symptoms (eg, transit vs pain). Patients with more straightforward, mild presentations respond well to gut-centric approaches,1,2 whereas complex presentations are likely to achieve improvement with treatments that address central nervous system influences on symptom presentation.3,4 HRQOL = health-related quality of life; IBS = irritable bowel syndrome.
      Table 4Irritable Bowel Syndrome Treatment Strategy: A Way Forward
      • 1.
        Evaluation
        • a.
          Consider conditions that mimic IBS (eg, celiac disease, microscopic colitis, bile acid diarrhea, pancreatic insufficiency, carbohydrate intolerances, medication side effects, postsurgical neoanatomy)
        • b.
          Assess for the presence of alarm symptoms
        • c.
          Evaluate for symptom triggers (eg, stressors, diet)
        • d.
          Explore presence of other functional GI (eg, functional dyspepsia) and non-GI disorders (eg, fibromyalgia), psychiatric comorbidity, and drug intolerances
        • e.
          Understand previous IBS treatment experiences
      • 2.
        Selection of Treatment Approach (Figure 2)
        • a.
          Predicated on symptom severity and dominant symptoms
        • b.
          Symptom severity (intensity, bother, effects on quality of life)
          • i.
            Mild symptoms, intermittent symptoms, low symptom burden: symptomatic or peripheral therapy
          • ii.
            Moderate symptoms: centrally acting neuromodulators, especially if symptomatic therapy does not provide adequate benefit
          • iii.
            Severe symptoms and those with comorbidities (non-GI functional disorders, psychiatric): both centrally acting neuromodulators and peripheral therapy
            • a.
              Concurrent affective disorders need to be managed
            • b.
              Other central therapies (cognitive and behavioral therapy, hypnosis, stress reduction) may need to be considered
        • c.
          Dominant symptoms (diarrhea, constipation, pain, other GI symptoms)
          • i.
            Constipation-predominant
            • a.
              Laxatives, fiber
            • b.
              Novel agents (linaclotide, lubiprostone)
          • ii.
            Diarrhea-predominant
            • a.
              Antidiarrheals
            • b.
              Alosetron
            • c.
              Address dysbiosis (rifaximin, probiotics)
            • d.
              Diet (low FODMAP)
            • e.
              Bile binders (cholestyramine, colesevelam)
            • f.
              Disaccharidases (lactase)
          • iii.
            Pain-predominant
            • a.
              Antidepressants (TCAs and SNRIs preferred)
            • b.
              Linaclotide when constipation present
            • c.
              Avoid narcotics
      • 3.
        Education/Therapeutic Alliance
        • a.
          Inform patient about etiopathogenesis
        • b.
          Reaffirm legitimacy of diagnosis; allay concerns about organic disease
        • c.
          Provide information about support organizations (International Foundation for Functional Gastrointestinal Disorders)
      FODMAP = fermentable oligosaccharides, disaccharides, monosaccharides, and polyols; GI = gastrointestinal; IBS = irritable bowel syndrome; SNRI = serotonin-norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant.

      Step 1: Gut Luminal and Mucosal Therapy

      Peripherally acting agents directed at the dominant symptom may be sufficient with mild symptoms. For instance, fiber, osmotic laxatives, and polyethylene glycol can be titrated in constipated patients, whereas antidiarrheal and anticholinergic agents can be used with diarrheal predominance. Approaches that affect the diet and intestinal milieu (antibiotics and probiotics) also may be beneficial.

      Step 2: Gut-directed Regulators

      Newer secretagogues (linaclotide, lubiprostone) are useful with constipation, and their favorable safety profile prompt early use. Pain suppression may lag behind the secretagogue effect of linaclotide by several weeks. Patients with refractory diarrhea may benefit from alosetron.

      Step 3: Centrally Acting Agents

      Centrally acting agents provide global syndromic benefit, complementing approaches initiated in earlier steps. Although tricyclic antidepressants have demonstrated success, contemporary antidepressants also have broad benefits. Comorbid affective disorders influence agent selection, for example, sertraline in comorbid anxiety and bupropion in comorbid depression. The side effect profile also can be targeted to the irritable bowel syndrome pattern, for example, diarrheagenic effect of sertraline and constipating effect of tricyclics. Adjunctive peripheral therapy (step 1) can overcome side effects (eg, constipation) if the agents are useful from an irritable bowel syndrome perspective. Antidepressants (particularly tricyclics, duloxetine, and venlafaxine) and psychotherapeutic approaches yield the greatest benefit in pain-predominant presentations. Severe, disabling symptoms, high nongastrointestinal symptom burdens, and psychiatric comorbidities are indications for early use of central therapies. Paradoxically, medications are tolerated poorly in these patients, and slow titration to effective doses is suggested.
      • North C.S.
      • Hong B.A.
      • Alpers D.H.
      Relationship of functional gastrointestinal disorders and psychiatric disorders: implications for treatment.

      Step 4: Adjunctive and Complementary Therapy

      When escalation of management is required, adjunctive and complementary approaches (eg, cognitive behavioral therapy, hypnosis, psychotherapy, and acupuncture) are implemented. Consultation with a health psychologist can affect coping mechanisms and reduce illness behavior. Supplementary nonpharmacologic therapies may be necessary with specific attention to stressors and active psychiatric symptoms (step 4).
      A multimodal strategy incorporating medications, nonpharmacologic options, and dietary modification often is required. Although prior treatments can be reinitiated, this may result in patient dissatisfaction; careful explanation of the intent of each recommendation (eg, advance to higher dose, longer duration of use) will maintain patient confidence and compliance.

      Irritable Bowel Syndrome Outcomes and Prognosis

      Narcotics have no role in irritable bowel syndrome management. Physical and psychologic dependence will result, and narcotic bowel syndrome can develop; ultimately, narcotics worsen abdominal pain and constipation. The hazards of narcotic use require open discussion because durable symptom improvement with narcotics is woefully low.
      • Kurlander J.E.
      • Drossman D.A.
      Diagnosis and treatment of narcotic bowel syndrome.
      Irritable bowel syndrome is a lifelong condition with exacerbations and remissions; although medications should be minimized to the extent possible, treatment trials are a critical component of management, each pursued for several weeks before switching therapies. Lack of response to a particular agent does not preclude response to another medication in the same class. Patient education and reassurance are essential; strong patient-doctor relationships lead to higher patient satisfaction and fewer return visits. Concerns about the legitimacy of irritable bowel syndrome diagnoses, the low potential for organic diagnoses, and current understanding of irritable bowel syndrome etiopathogenesis should be addressed directly.
      Establishing realistic expectations early is critical; the goal of irritable bowel syndrome treatment is to improve gastrointestinal symptoms and quality of life, not necessarily complete “cure.” Symptom remission may allow reduction or discontinuation of medication; flares necessitate reintroduction of previously successful treatments. Through the implementation of the approaches outlined, a majority of patients with irritable bowel syndrome will experience symptom improvement.

      Conclusions

      Irritable bowel syndrome is a common symptom-based diagnosis, with several etiopathophysiologic mechanisms. Implementation of an informed evaluation leads to high diagnostic accuracy. Treatment strategies that consider symptom severity and dominant symptoms, using multifaceted pharmacotherapeutic and nonpharmacologic and complementary approaches, provide for effective irritable bowel syndrome management. Coupled with education, reassurance, and support, even the most challenging patients with irritable bowel syndrome will experience improvement in symptoms and quality of life.

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      Linked Article

      • Irritable Bowel Syndrome: Modern Concepts and Management Options
        The American Journal of MedicineVol. 129Issue 2
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          I read with great interest the comprehensive review by Sayuk and Gyawali1 on irritable bowel syndrome. They carefully analyzed modern treatment options with peripherally acting agents for the 2 main subtypes by predominant stool pattern, namely the constipation-predominant and diarrhea-predominant subtypes. Surprisingly, they did not similarly consider treatment options for mixed irritable bowel syndrome, a subtype defined in Table 2, or for alternating irritable bowel syndrome, which refers to a change between diarrhea-predominant and constipation-predominant forms over time.
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