INTRODUCTION
Irritable bowel syndrome (IBS) often presents with recurring abdominal pain, bloating, diarrhea, or constipation with an estimated pooled prevalence of 4.1% to 10.1%,1,2 respectively. In the western world IBS is twice more common in females than males.1,2
IBS has a substantial impact on healthcare burden, both to patients and society, in terms of daily symptoms, quality of life (QoL), work productivity, and healthcare costs.3-5 Many patients experience chronic, disruptive symptoms for many years prior to seeking health care, and typically report lengthy and complex treatment histories.4,6,7 Results from the IBS in America survey indicate that most patients with constipation-predominant IBS (IBS-C) experience symptoms at least 4 to 6 days per week,7 while another survey found that over half of patients with diarrhea-predominant IBS (IBS-D) reported experiencing fecal urgency most of the time.6 Abdominal pain is an important symptom and a key driver of health care seeking behavior.4 The main QoL domains affected by IBS includes general health, social functioning, and mental health.8,9
IBS may be caused by multiple pathophysiological mechanisms, including disordered gut-brain interactions, abnormalities in gastrointestinal (GI) motility, visceral hypersensitivity (a cardinal dysfunction), altered intestinal permeability, immune dysfunction, and gut dysbiosis.9-13 Genetic polymorphisms and environmental factors, including dietary and enteric, also play a role.12 Acute viral or bacterial gastroenteritis remains a strong risk factor for IBS, with 10% of patients reporting IBS after acute infections (i.e., post-infectious IBS).12 Whether IBS symptoms arise because of abnormal stress response to infectious and/or inflammatory gut responses, or from gut dysbiosis causing release of inflammatory mediators that affect the gut-brain axis merits further studies.12 The diagnostic approach and management of IBS, under the three main subcategories of IBS-D and IBS-C, and bloating, will be discussed. An overlap between these categories and other forms of IBS including IBS-M (mixed IBS with diarrhea and constipation) and IBS-U (undifferentiated IBS) may also exist.9,10

Clinical Approach to IBS-D
Diagnostic tests
IBS-D can usually be diagnosed with the help of Rome diagnostic criteria (Table 1, 2) without performing an array of diagnostic tests, although selected testing is appropriate in some patients to distinguish organic diseases from lower gastrointestinal motility disorders.9,10 (Figure 1) Key organic conditions that should be excluded in patients with suspected IBS-D include inflammatory bowel disease (IBD), hormonal disturbances, enteric infections, colorectal cancer, and disorders associated with malabsorption such as celiac disease, bile acid diarrhea, or carbohydrate maldigestion.9,10,13 A complete blood count is recommended to identify elevated white blood cell count, or anemia, while measures of systemic inflammation such as C-reactive protein (CRP) or fecal calprotectin can help discriminate between IBS and IBD.9,14 Given its low yield in this setting,15 routine colonoscopy is not recommended in the absence of alarm features.9 A small proportion of patients with suspected IBS-D may have microscopic colitis.14,15 Hence, colonoscopy with random colon biopsies is recommended.14
Hydrogen and methane breath tests can be useful in diagnosing various food intolerance syndromes, small intestinal bacterial overgrowth (SIBO) or small intestinal fungal overgrowth (SIFO), which are commonly associated with IBS-like symptoms.16,17 Despite significant heterogeneity in test performance, preparations, and indications, a recent consensus of experts and the American College of Gastroenterology (ACG) clinical practice guidelines concluded that breath hydrogen and methane testing can be useful in diagnosing not only carbohydrate maldigestion and SIBO, but also in assessing patients with bloating and methane-associated constipation.16,17 Since 25% of patients with IBS-D have evidence of bile acid diarrhea, regardless of cholecystectomy,18 tests such as 23-seleno-25-homotaurocholic acid retention test (75SeHCAT) or testing for 7-C4, a bile acid precursor, may be useful, especially to identify patients who may benefit from bile acid binding resins.
The value of celiac screening remains unclear. Current ACG guidelines recommend screening patients with tissue transglutaminase antibody (TtG) test,19 which is supported by a recent meta-analysis demonstrating a significantly higher prevalence of biopsy-proven celiac disease among all subtypes of IBS compared with controls.20 Likewise on a case-by-case basis, for example recent foreign travel, or antibiotic use, appropriate consideration should be given for stool evaluation of ova, parasites, culture and C. difficile toxin evaluation.
Management of IBS-D
A diet low in fermentable oligo-, di-, and monosaccharides, and polyols (FODMAPs) has become popular and has been evaluated.10,21,22 Meta-analysis of 7 RCTs found a significant effect of a low FODMAP diet in improving overall symptoms of IBS,10 with overall improvement in about half to two-thirds of patients.22 The most likely symptoms to respond include bloating and abdominal pain, and diarrhea is more likely to improve than constipation.22 A two-to-four-week trial is usually sufficient to assess response, with many patients responding within the first two weeks of FODMAP restriction. A recent network meta-analysis showed that low FODMAP diet was as superior to BDA/NICE diet for bloating and distension, and it is better than habitual diet for global gas symptom, although here was a higher risk of bias.23
Further, the long-term efficacy of this diet is unknown. A low FODMAP diet is not intended to be a long-term treatment strategy, but rather a tool for identifying patients who are sensitive to FODMAPs so that some of these foods can be systematically reintroduced to determine which foods are triggers and individualize diets accordingly.22,23 This process is best guided by a dietitian with expertise in caring for patients with GI disorders. An alternative approach is to perform fructose, lactose, fructan or sucrose breath tests,24,25 and/or disaccharidase mucosal enzyme assay26 to precisely determine the underlying etiology with one or more enzyme deficiency or food intolerance(s), and then provide tailored nutrition advice.25
Antidiarrheals and antispasmodics: Loperamide, a peripheral µ-opioid receptor agonist, is often recommended for patients with IBS-D.27 Although an effective antidiarrheal, there is no evidence supporting its efficacy in relieving abdominal pain, bloating, or global IBS symptoms.10 (Table 3) Similarly, despite being used for decades to treat abdominal pain associated with IBS, the evidence supporting the use of antispasmodics is modest.9,27 However, these agents do appear to provide some short-term benefit in IBS, but their use can be limited by dose-dependent anticholinergic adverse effects (e.g., constipation, fatigue, dry mouth, dizziness, blurred vision).27 Peppermint oil, which causes smooth muscle relaxation by blocking calcium channels, has been found to improve IBS symptoms in a small number of trials.10 In particular, an enteric-coated, sustained-release formulation of peppermint oil, IB Gard®, improved symptom scores in an RCT involving 72 patients with IBS-D/M, with significant improvement compared to placebo, and within 24 hours 28. Overall, the AGA guidelines gave this class a conditional and either low or very low evidence. (Table 3D)
Recurrent abdominal pain, on average, ≥1 day per week in the last 3 months, associated with ≥2 of the following criteria: |
1. Related to defecation 2. Associated with a change in frequency of stool 3. Associated with a change in form (appearance) of stool |
Criteria fulfilled for the last 3 months with symptom onset ≥6 months |
Antidepressants: Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are useful in relieving pain and overall symptoms in IBS.27 These medications work centrally and peripherally via pain perception, visceral hypersensitivity, and GI motility. Although the efficacy of antidepressants according to predominant stool pattern has not been well studied, TCAs may be most appropriate in IBS-D given their ability to slow colonic motility and their mildly constipating effects.27 The serotonin and norepinephrine reuptake inhibitors (SNRIs) have not been studied adequately in this population. Given the diarrhea-predominant symptoms, a trial of low-dose TCA would be an appropriate option as these neuromodulators are very effective for treatment of pain. The AGA guidelines gave a conditional, low evidence recommendations for these agents. (Table B) A recent large community based RCT showed that a titrating dose of amitriptyline (10-30 mg/day) for 6 months, was superior to placebo in improving IBS symptoms.29
Management of bloating: Bloating is intricately linked and often associated with IBS.10,17,30 To that end, restriction of dietary FODMAPs has been found in studies of varying design to decrease bloating in a large proportion (50-82%) of patients.10,30 Another strategy is the use of probiotics, which are defined as attenuated bacteria or bacterial products that are beneficial to the host. Based on data from 37 RCTs involving 4403 patients, the ACG Task Force on IBS determined that probiotics have low quality of evidence and therefore gave a weak recommendation for treatment of IBS, with possible benefit on bloating and flatulence, rather than on bowel urgency or function.10 However, due to the poor quality and heterogeneity of the evidence, recommendations regarding the use of particular strains or species, or the subtype of IBS most likely to respond, could not be made.10 Also, a recent study cautioned against indiscriminate probiotic use as it may lead to colonization of probiotic organisms in the small bowel causing small intestinal bacterial overgrowth (SIBO), D-lactic acidosis, bloating and brain fog.31
Recent change in bowel habit (< 3 months) Age ≥50 years, no previous colon cancer screening, and presence of symptoms Unintentional weight loss Evidence of overt GI bleeding(i.e., melena or hematochezia) Nocturnal pain or passage of stools Family history of colorectal cancer, celiac disease or IBD Palpable abdominal mass or lymphadenopathy Evidence of iron-deficiency anemia Positive test for fecal occult blood |
GI: gastrointestinal; IBD: inflammatory bowel disease.
Rifaximin, an oral, non-absorbable, broad-spectrum antibiotic, has been extensively evaluated in IBS and found to improve bloating.10,32 Based on data from 6 RCTs involving 2441 non-constipated IBS patients, the ACG Task Force recommends rifaximin for improvement of global IBS symptoms as well as bloating.10 Although the precise mechanism for its benefit in IBS remains unclear, rifaximin appears to have beneficial effects on GI symptoms of diarrhea, pain and bloating, mucosal inflammation, and stabilization of the gut microbiota. Further, preclinical evidence suggests that the effects of rifaximin in IBS may involve mechanisms beyond the gut microbiota, including the modulation of proinflammatory cytokines and intestinal permeability.32
Rifaximin is approved in a 14-day regimen for the treatment of IBS-D and up to two retreatments in those who experience recurrence. Rifaximin is well tolerated, with a safety profile similar to that of placebo.32 The potential for an increased risk for Clostridium difficile infection and/or the emergence of microbial resistance has been reassuring.10,32 The AGA guidelines gave Rifaximin a conditional, moderate evidence recommendation.27 (Table 3D)
Specific therapies for IBS-D: Alosetron is a selective serotonin 5-HT3 receptor antagonist that improves global IBS symptoms and abdominal pain.10,27 Recently, a network meta-analysis of 18 RCTs involving various therapies (alosetron, ramosetron, rifaximin, eluxadolione) ranked alosetron first in efficacy for achieving the composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms, and effect on stool consistency in patients with IBS-D/M.27,33 However, it’s use has been limited by the small risk of ischemic colitis (1.03 cases per 1000 patient-years) and serious complications of constipation (0.25 cases per 1000 patient-years),34 leading to the restriction of its use to women with severe IBS-D who have not responded to conventional therapies.34 Although marketed under a Risk Evaluation and Mitigation Strategy program, requirements for the program have been updated to make it less onerous for prescribers than when it was first initiated.27 Alosetron was afforded a conditional recommendation with moderate certainty in evidence by the AGA.27 (Table 3B)
Eluxadoline is an oral, locally acting, mixed μ- and κ-opioid agonist/δ-opioid receptor antagonist approved for use in adults with IBS-D.35,36 Unlike pure µ-opioid receptor agonists, this agent reduces visceral hypersensitivity without completely disrupting intestinal motility, theoretically decreasing the potential for medication-related constipation.35,36 Meta-analysis of data from three large RCTs demonstrated significant benefits of eluxadoline on stool consistency and overall symptom improvement IBS-D patients but failed to demonstrate a clear effect on abdominal pain.10 However, subsequent analysis of the pivotal trials37 and a phase 4 study36 found eluxadoline to be effective in improving abdominal and stool consistency in IBS-D patients reporting inadequate symptom response to loperamide. Eluxadoline has been relatively well tolerated in clinical trials, with the most common adverse effects being constipation, nausea, and vomiting.10,36,38 However, due to the risk of pancreatitis, this agent is contraindicated in patients without a gallbladder, known or suspected biliary duct obstruction or sphincter of Oddi disease/dysfunction, alcohol use, history of pancreatitis, severe hepatic impairment, and severe constipation or its sequelae.38 The AGA assessment gave eluxadoline a conditional recommendation with moderate certainty.27,35 (Table 3B)
Drug | Class | N | Dose | Side Effects | Efficacy (Drug vs. Placebo) |
Eluxadoline | Mixed μ/κ Agonist & Antagonist | 1617 (2 RCT) | 75/100 mg qd | Constipation, nausea, pain | 27.2 vs 16.7 %, RR 0.87 (0.8-0.9) |
Rifaximin | Nonabsorbable Broad Spectrum antibiotic | 1258 (3 RCT) | 550 MG TID | Nausea, URI, UTI | RR 0.85% (0.8-0.9) |
Rifaximin | GCC agonist | 2438/636 (1 RCT – 2 PHASES) | 550 mg/tid | Nausea, URI, UTI N. Pharyngitis | 38% vs 31%; RR 0.9 (0.8-1) |
Alosetron | 5 HT3 antagonist | 4227 (8 RCT) | 0.5-1 mg bid | Ischemic Colitis, constipation | RR 0.6 (0.5-0.67) |
Loperamide | μ agonist | 2883 (2 RCT) | 2 or 6 mg bid | Headache, nausea, diarrhea | RR 0.4 (0.2-0.8) |
Amitriptyline Desipramine Imipramine | Tricyclic Antidepressant | 523 (8 RCT) | Variable | Constipation/sleep/High Withdrawal rate | RR 0.67 (0.5-0.8) |
Fluoxetine Paroxetine | SSRI | 7 RCT | Variable | Weight gain, dreams | RR 0.74 (0.5-1.06 |
12 drugs (Cochrane) | Antispasmodics | 2983 (22 RCT) | Variable | Dry mouth, Dizziness, vision | RR 0.74 (0.59-0.9) |
5 HT3 = 5 Hydroxy Tryptamine 3; SSRI = Selective Serotonin receptor inhibit.
RCT = Randomized controlled trial; qd = once/day; Bid = twice a day; TID = three times/day.
UTI = Urinary tract infection; RR = Relative risk ratio
Clinical Approach to IBS-C
Diagnostic Tests for IBS-C: A first step is to obtain a detailed clinical history, and perform a digital rectal exam,40 and physical examination, combined with selected tests to exclude organic disease. (Figure 1). Further, evaluation of the pathophysiology of constipation may prove useful.9,41 It is important to characterize what a patient means by the term constipation; is it altered stool frequency or is it difficulty with defecation or both. Assessment of incomplete evacuation and stool consistency using a Bristol stool scale is important as well as associated features, such as degree of straining during defecation and use of digital maneuvers to assist defecation.9 It is essential to perform a digital rectal exam,40 which can help identify fecal impaction, anal stricture, rectal mass, and/or dyssynergia.9,39,42 Patients with paradoxical anal contraction on straining or inadequate push effort or anal/puborectalis relaxation should be referred for anorectal physiologic testing.39,42
Again, the presence of key alarm symptoms (e.g., unintentional weight loss, rectal bleeding) and whether patient has undergone recent screening colonoscopy per national recommendations are important. Assessment for hypothyroidism or hypercalcemia with a serum TSH and serum calcium may be useful.9 Although IBS-C and CIC are among the most common overlapping disorders associated with chronic constipation, it is important to exclude secondary causes of constipation such as drugs, metabolic disorder, neurological disorders and others.42
Once alarm features and secondary causes for a constipation have been excluded, the Rome IV criteria can be useful to diagnose IBS-C.9 (Tables 2,3)
General Management and Diet
Patient should be educated about IBS and advised to increase fluid intake, and maintain a fiber-rich diet, and regular exercise and reduce daily stressors. Poorly fermentable, soluble fiber (e.g., psyllium) is a recommended, evidence-based treatment for IBS-C.9,41 In contrast, insoluble fiber (e.g., bran) has no significant effect on IBS symptoms and on the contrary, may increase pain and bloating.10,41 Although an appropriate first-line treatment, fiber supplementation should be introduced gradually, starting with low doses and titrating slowly as tolerated to minimize unwanted GI effects (bloating, flatulence, and abdominal discomfort).10,44 Patients should also be educated that, unlike stimulant laxatives, response to fiber may take several weeks.42
New or Updated Recommendations | Strength of Recommendation | Certainty in Evidence |
1. In patients with IBS-D, the AGA suggests using eluxadoline Implementation remark; eluxadoline is contraindicated in patients without a gallbladder, or those who drink more than 3 alcoholic beverages per day | Conditional | Moderate |
2a. In patients with IBS-D, the AGA suggests using rifaximin | Conditional | Moderate |
2b. In patients with IBS-D with initial response retreatment with rifaximin recurrent symptoms, the AGA suggests retreatment with rifaximin | Conditional | Moderate |
3. In patients with IBS-D, the AGA suggests using alosetron | Conditional | Moderate |
4. In patients with IBS-D, the AGA suggests using loperamide | Conditional | Moderate |
5. In patients with IBS, the AGA suggests using TCAs | Conditional | Moderate |
6. In patients with IBS, the AGA suggests against using SSRIs | Conditional | Moderate |
7. In patients with IBS, the AGA suggest using antispasmodics | Conditional | Moderate |
*For all recommendation statements, the comparator was no drug treatment.
Laxatives and fruits: Stimulant laxatives (senna, bisacodyl, castor oil, cascara, and aloe) help to produce bowel movements by decreasing water absorption and stimulating intestinal motility, either directly or indirectly through release of prostaglandins.42,44 These agents are often used on a rescue basis, such as in patients who have not defecated in several days, or more regularly if required.45 Based on data from 2 RCTs, the AGA considers sodium picosulfate and bisacodyl to be effective for CIC,46 although their use can be limited by poor tolerability, particularly regarding diarrhea and abdominal cramping. There is insufficient evidence to recommend the use of other stimulant laxatives for CIC, and similarly, there are no RCTs of stimulant laxatives in IBS-C.41
Polyethylene glycol (PEG) is an osmotic laxative that extracts fluid into the intestinal lumen to soften stools and accelerate colon transit. 47 The short- and long-term efficacy of PEG has been well-established in patients with CIC,47 with efficacy and safety established up to 6 months in an RCT47 and 24 months in a retrospective trial. Its efficacy in IBS-C, however, is less clear. (Table 4A) Data from two small RCTs found that PEG improved stool frequency in patients with IBS-C, but not pain or other IBS-related symptoms.10,48 Based on these data, the ACG recommends against the use of PEG for overall symptom improvement in IBS patients.10 Recently Kiwi fruit has been shown to be useful in improving IBS symptoms in an RCT.49
Antidepressants: Both TCAs and SSRIs are effective in relieving pain and overall symptoms in IBS.46 Given their prokinetic and anxiolytic effects, an SSRI is more appropriate option for constipation-related symptoms. These agents should be initiated at low doses and takes 4 to 8 weeks to achieve therapeutic response.46 (Table 4A)
Specific Therapies for IBS-C: Several specific therapies, (lubiprostone, linaclotide, plecanatide, and tenapanor) have been FDA approved over the last decade for the treatment of IBS-C.46,50-56 These therapies include secretagogues that act on intestinal enterocytes to stimulate net efflux of ions and water into the intestinal lumen, accelerate intestinal transit, and facilitate ease of defecation. These agents significantly improve bowel and abdominal symptoms in IBS-C,46 and are approved for this use.46,50-56 These agents were afforded a conditional recommendation with moderate certainty by the AGA guidelines. (Table 4B)
Lubiprostone was the first compound approved in 2006. It is a prostaglandin E1 derivative that acts on type 2 chloride channels (ClC2) of small intestinal enterocytes to increase secretion of chloride and fluid into the intestinal lumen.10 This agent is approved at dosages of 8 µg twice daily. The most common adverse effect with lubiprostone is dose-related nausea, occurring in 8% of patients receiving 8 µg and 24 µg twice daily, in pivotal trials of IBS-C and CIC compared with 4% and 3% of patients receiving placebo.50 Lubiprostone should be taken with food and water to minimize nausea and treatment can be initiated at lower doses and titrated upward as needed.46
Linaclotide and plecanatide are guanylate cyclase (GC)-C agonists that produce cyclic GMP intracellularly leading to activation of chloride ion secretion through the cystic fibrosis transmembrane regulator (CFTR), increasing fluid secretion into the GI tract and accelerating intestinal transit.51,52 Additionally, because GC-C pathways are involved in modulating pain fiber activity,53 these agents have effects on the abdominal pain and sensory symptoms of patients with IBS-C.54,55 In clinical trials, however, improvement in stool frequency tends to occur earlier (i.e., within a week of treatment initiation) with linaclotide compared with improvement in abdominal pain and bloating, which make take up to 8 to 12 weeks.51 A recent placebo controlled RCT study showed that linaclotide improves abdominal pain in patients IBS-C by improving rectal hypersensitivity and attenuating the signals from the rectum to the brain.55
Drug | Class | N | Dose | Side Effects | Efficacy (Drug vs. Placebo) |
Tenapanor | NHE3 channel Inhibitor | 1372 (3 RCT) | 50 mg bid | Diarrhea | 34 vs. 27%, RR, 0.84 (0.79-0.94) |
Plecanatide | Guanylate Cyclase C (GCC) agonist | 1632 (3RCT) | 3 mg daily | Diarrhea, bloating | RR, 0.87 (0.83-0.92) |
Linaclotide | GCC agonist | 2443 (3 RCT) | 290 mcg/day | Diarrhea, bloating | RR, 0.81 (0.77-0.85) |
Lubiprostone | CCI2 activator | 1154 (3 RCT) | 8 mcg bid | Nausea, diarrhea | RR, 0.88 (0.79-0.96) |
Tegaserod | 5 HT4 agonist | 2883 (4 RCT) | 2 or 6 mg bid | Headache, nausea, diarrhea | 35 vs. 24%, RR, 0.87 (0.81-0.93) |
PEG | Osmotic | 139 (1 RCT) | 30 g daily | Bloating, diarrhea | RR, 0.9 (0.66-1.2) |
Amitriptyline Nortriptyline Imipramine Desipramine Simipramine | TCA | 523 (8 RCT) | Variable | Constipation, sleep | RR, 0.67 (0.54-0.82) |
Paroxetine Citalopram | SSRI | 7 RCT | Variable | Weight gain, dreams | RR, 0.74 (0.52-1.06) |
12 drugs (Cochrane) | Antispasmodics | 2983 (22 RCT) | Variable | Dry mouth | RR, 0.67 (0.55-0.80) |
Both linaclotide and plecanatide are approved at once-daily doses for use in IBS-C and CIC.46 (Table 9) Diarrhea is the most common adverse effect, which is usually mild and leads to few treatment discontinuations. Diarrhea can be managed by administering linaclotide 30 to 60 minutes before breakfast,46 or by starting with a low dose (72 µg/day) and titrating up to 290 mg/day.
New or Updated Recommendations | Strength of Recommendation | Certainty in Evidence |
1. In patients with IBS-C, the AGA suggests using tenapanor | Conditional | Moderate |
2. In patients with IBS-C, the AGA suggest using plecanatide | Conditional | Moderate |
3. In patients with IBS-C, the AGA recommends using linaclotide | Strong | High |
4. In patients with IBS-C, the AGA suggests using tegaserod Implementation remark: Tegaserod was reapproved for women under the age of 65 years without a history of cardiovascular ischemic events (such as myocardial infarction, stroke, TIA, or angina) | Conditional | Moderate |
5. In patients with IIBS-C, the AGA suggests using lubiprostone | Conditional | Low |
6. In patients with IIBS-C, the AGA suggests using PEG laxatives | Conditional | Low |
7. In patients with IBS, the AGA suggests using TCAs | Conditional | Low |
8. In patients with IBS, the AGA suggest against using SSRIs | Conditional | Low |
9. In patients with IBS, the AGA suggests using antispasmodics | Conditional | Low |
*For all recommendation statements, the comparator was no drug treatment.
TIA: Transient ischemic Attack; PEG: Polyethylene Glycol; TCA: Tricyclic Antidepressants; SSRI: Selective Serotonin Receptor Reuptake Inhibitor.
Tenapanor is a new class of drug and is a sodium hydrogen exchanger 3 blocker that inhibits sodium absorption in the intestinal lumen.46,56 In 2 large clinical trials, tenapanor 50 mg BID was superior to placebo in improving IBS-C symptoms. It has been approved for IBS-C.46,56 Its main side effect is diarrhea.
CONCLUSIONS
IBS is a common disorder that imposes considerable health care burden. Dissatisfaction with current therapies remained but progress has been made on several fronts. Advances in understanding of the pathogenesis of these disorders have paved the way for new treatments. Recent evidence on the role of certain foods causing symptoms, and carefully planned dietary intervention, particularly the low-FODMAP diet, as a therapeutic strategy may be useful for many IBS patients. The best clinical trial evidence for IBS-D supports the use of alosetron, TCAs, peppermint oil, rifaximin, and eluxadoline. Although the predominance of abdominal pain differentiates IBS-C from chronic constipation, significant overlap exists, and treatment options are largely similar. First-line treatment of IBS-C/chronic constipation typically consists of diet and lifestyle modifications, along with nonprescription laxatives (soluble fiber, PEG). High-quality evidence supports the efficacy of prosecretory agents (lubiprostone, linaclotide, plecanatide), and NHE3 blocker tenapanor for the treatment of IBS-C. Cognitive behavioral therapy, especially using home-based APPs is gaining popularity and its wider availability will improve access to this therapy along with the stress-reduction therapies such as yoga and meditation, but these interventions need more evidence.
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