William D. Chey, MD
Michigan Medicine

Key Takeaways

  • Clinicians may confidently diagnose irritable bowel syndrome (IBS) if symptoms are consistently present once weekly for a period of 3 to 6 months. Testing may be indicated to exclude other diagnoses, but a diagnosis of IBS should not be presented as one of exclusion.
  • The most evidence-based lifestyle treatment for IBS is to follow a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, which clinicians should implement in 3 distinct phases — restriction, reintroduction, and personalization — to offer the best chance of symptom improvement.
  • Patients experiencing IBS with predominant constipation (IBS-C), second-line treatment medications should be prescribed after a careful analysis of the patient’s most persistent symptoms — plecanatide for pain and bloating, tegaserod for dyspepsia — while steering clear of medications such as lubiprostone if the patient exhibits symptoms such as nausea.
  • Additional second-line treatments, including the use of neuromodulators, peppermint oil, or cognitive behavioral therapy (CBT), may offer additional relief to patients.
  • Ongoing care for the management of IBS should follow a team approach, ensuring patients continue to meet with providers, dietitians, and psychologists who specialize in gastrointestinal (GI) health.

William D. Chey, MD, is a professor of medicine, the director of the GI Physiology Laboratory, and the co-director of the Michigan Bowel Control Program at the University of Michigan in Ann Arbor.  His clinical areas of interest include functional bowel and motility disorders, including IBS, constipation, functional heartburn, noncardiac chest pain, dysphagia, dyspepsia, and fecal incontinence. Additional areas of interest include H pylori infection and acid-related disorders such as gastroesophageal reflux disease and peptic ulcer disease.

There seems to be a mismatch between the views of clinicians and patients regarding the diagnosis of IBS, which can present a challenge when it comes to the usefulness of the patient-clinician interaction. What practices can help create a more encouraging, meaningful, and engaged consultation?

Patients want a confident diagnosis from their provider. To most health care providers, the word “confident” does not belong in the same sentence as the diagnosis of IBS. I see patients almost every week who have seen multiple providers and yet they have never been given a formal diagnosis of IBS. Even more commonly, patients will tell me, “My doctor did a lot of tests that were all negative, so he/she thinks I have IBS.” There is so much to unpack from this statement. It reflects the fact that most providers think of IBS as a diagnosis of exclusion and not a “real” condition. That is reflected by the provider “thinking” the patient has IBS. Particularly for a condition that doesn’t have a definitive blood or stool test, the lack of confidence and imprecision of the language used by providers undermine a patient’s confidence in their diagnosis. 

More than 70% of community-based providers believe that IBS is a diagnosis of exclusion.1 What is the justification for a positive diagnosis of IBS as opposed to a diagnosis of exclusion? What tests should be performed on a patient presenting with IBS symptoms to improve time to initiate the appropriate therapy? 

Often, IBS is a symptom-based diagnosis that relies on the presence of recurrent bouts of abdominal pain and altered bowel habits in the form of hard or lumpy stools. Patients can present with IBS-C, IBS with diarrhea (IBS-D), or a mixture of both (IBS-M). According to the Rome IV criteria, patients with IBS suffer with symptoms at least once weekly for 3 to 6 months. There is no definitive blood or stool test for IBS. The recommended tests are mostly intended to rule out organic diseases that can mimic symptoms of IBS. The tests don’t make the diagnosis of IBS but they do help providers to be more confident that patients with typical IBS symptoms do indeed suffer with IBS.
 
Recommended testing differs on the basis of whether a patient has IBS-D, IBS-C, or IBS-M. In patients with IBS-D and IBS-M, testing is recommended to rule out celiac disease and inflammatory bowel diseases. Some providers are advocating to test patients with IBS-D for bile acid diarrhea or small intestinal bacterial overgrowth. For patients with IBS-C, testing is recommended to evaluate for pelvic floor dysfunction when symptoms persist despite diet, lifestyle, and medical therapies. All individuals, including patients with IBS, should undergo age-appropriate colon cancer screening.

What lifestyle measures and dietary modifications could help patients manage IBS-C, IBS-D, or IBS-M?

Common sense dietary recommendations such as eating smaller meals, avoiding carbonated beverages, artificial sweeteners, and being mindful of fresh fruit and resistant starch intake may provide some relief. While these measures can offer benefit to some patients with IBS, the most evidence-based diet intervention for IBS is the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet.
 
This diet excludes short-chain sugars that the human small intestine has difficulty absorbing or simply cannot absorb and allows the sugars to reach the colon where they are fermented by bacteria to produce short-chain fatty acids and gases that can serve as important triggers for symptoms in patients with IBS. Numerous studies now show that approximately half of IBS patients, particularly those with IBS-D, experience an improvement in their overall burden of gut symptoms, particularly pain and bloating, after reducing dietary FODMAP intake.2 The low FODMAP diet is ideally administered with the help of a trained GI dietitian and consists of 3 phases:3

1. Restriction. FODMAPs are largely restricted from the diet. This phase typically lasts for 4 to 6 weeks and should be viewed as a “diagnostic test” to determine if a patient with IBS is sensitive to FODMAPs.

2. Reintroduction. Patients with IBS who improve with FODMAP restriction should undergo the reintroduction of foods that contain individual FODMAPs to determine their specific sensitivities. Most often, patients are sensitive to fructans, which can be found in onions, garlic, and wheat.

3. Personalization. Information gathered in the reintroduction phase is then used to personalize and liberalize each patient’s version of the low FODMAP diet.
 
There are numerous other diets that are under development or being tested in clinical trials. Time will tell which ones prove to be effective, but it is likely that diets other than the low FODMAP diet will offer benefits to subgroups of patients with IBS. Some of the more exciting research is focusing on the development of diagnostic tests that can guide dietary recommendations in patients with IBS.

Most providers think of IBS as a diagnosis of exclusion and not a ‘real’ condition… Particularly for a condition that doesn’t have a definitive blood or stool test, the lack of confidence and imprecision of the language used by providers undermine a patient’s confidence in the diagnosis of IBS.

How can a clinician decide when linaclotide, lubiprostone, plecanatide, tegaserod, or tenapanor would yield the best results for a patient with IBS-C? 

There are no head to head trials between the available prescription medications for the management of IBS-C. Choice of treatment should be individualized based upon a patient’s symptom profile. For example, guanylyl cyclase-C agonists like linaclotide and plecanatide offer benefits to pain, bloating, and constipation.Patients with comorbidities such as concurrent dyspepsia might benefit from the upper and lower prokinetic properties of tegaserod. Lubiprostone must be avoided in patients with significant nausea. Tenapanor increases intestinal secretion by blocking sodium absorption and has been approved by the US Food and Drug Administration (FDA) for use in patients with IBS-C.5,6

When and why would a patient benefit from off-label use IBS medications, such as selective serotonin reuptake inhibitors (SSRIs), or antispasmodics such as peppermint oil?

Peppermint oil offers antispasmodic properties and experimentally has antibacterial and anti-inflammatory properties, all of which could impact symptoms in patients with IBS. Enteric-coated preparations help reduce the incidence of heartburn, which is the most common side effect of peppermint oil.7 Many other supplements, such as glutamine, turmeric, and CBD oil are being evaluated as treatments for patients with IBS.
 
Neuromodulators, including low dose tricyclic agents (TCAs), SSRIs, and selective norepinephrine reuptake inhibitors (SNRIs) can be very useful as second-line treatments in patients with IBS. Use of TCAs and SSRIs can be particularly useful in patients with IBS-D.8,9


Lubiprostone adverse effects
Flip
Adverse effects commonly reported with lubiprostone include nausea, stomach pain, vomiting, heartburn, headache, dizziness, swelling, and chest discomfort.

Have you seen symptom improvements when patients with IBS undergo cognitive behavioral therapy (CBT) or gut-directed hypnotherapy (GDH)?

There is ample evidence to support the benefits of behavioral therapies in patients with IBS. In particular, CBT and GDH reduce the severity of symptoms in many patients with IBS.9,10 The best candidates for behavioral therapies are patients with insight into the relationship between stress or anxiety and their IBS symptoms. Unfortunately, most GI practices in the United States do not have access to a trained GI psychologist. Digital CBT and GDH programs administered via mobile app or the web may provide a scalable solution to the lack of human resources. 

After crafting initial treatment recommendations, what form of follow-up care should patients with IBS receive?

I strongly believe that caring for patients with IBS is a “team sport.” Integrated care models that incorporate a team of providers, dietitians, and psychologists who specialize in GI health could lead to improved outcomes when compared with traditional care offered by a GI provider alone.

This Q&A was edited for clarity and length.

Disclosure

William D. Chey, MD, reported affiliations with AbbVie Inc.; Allakos Inc.; Alnylam Pharmaceuticals, Inc.; Arena Pharmaceuticals, Inc.; Biomerica, Inc.; Gemelli Biotech; Ironwood Pharmaceuticals, Inc.; Nestle Health Sciences; QOL Medical, LLC; Phathom Pharmaceuticals, Inc.; Progenity, Inc.; Redhill Biopharma Ltd.; Salix Pharmaceuticals, Ltd./Valeant Pharmaceuticals International, Inc.; Takeda Pharmaceutical Company Limited; Urovant Sciences, Inc.; Vibrant Pharma Inc.; Commonwealth Diagnostics International, Inc.; GI on Demand; and Modify Health. 

References

  1. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44. doi:10.14309/ajg.0000000000001036
  2. Staudacher HM, Whelan K, Irving PM, Lomer MC. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndromeJ Hum Nutr Diet. 2011;24(5):487-495. doi:10.1111/j.1365-277X.2011.01162.x
  3. Chey WD, Keefer L, Whelan K, Gibson PR. Behavioral and diet therapies in integrated care for patients with irritable bowel syndromeGastroenterology. 2021;160(1):47-62. doi:10.1053/j.gastro.2020.06.099
  4. Menees SB, Franklin H, Chey WD. Evaluation of plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation in patients 65 years or olderClin Ther. 2020;42(7):1406-1414.e4. doi:10.1016/j.clinthera.2020.05.012
  5. Chey WD, Lembo AJ, Yang Y, Rosenbaum DP. Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: a 26-week, placebo-controlled phase 3 trial (T3MPO-2)Am J Gastroenterol. 2021;116(6):1294-1303. doi:10.14309/ajg.0000000000001056
  6. Ardelyx announces US launch of IBSRELA®, a new first-in-class treatment for IBS-C in adults. News release. Ardelyx, Inc. April 4, 2022. Accessed May 4, 2022. https://www.prnewswire.com/news-releases/ardelyx-announces-us-launch-of-ibsrela-a-new-first-in-class-treatment-for-ibs-c-in-adults-301516463.html
  7. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysisJ Clin Gastroenterol. 2014;48(6):505-512. doi:10.1097/MCG.0b013e3182a88357
  8. Ford AC, Lacy BE, Harris LA, Quigley EMM, Moayyedi P. Effect of antidepressants and psychological therapies in irritable bowel syndrome: an updated systematic review and meta-analysisAm J Gastroenterol. 2019;114(1):21-39. doi:10.1038/s41395-018-0222-5
  9. Kułak-Bejda A, Bejda G, Waszkiewicz N. Antidepressants for irritable bowel syndrome-a systematic review. Pharmacol Rep. 2017;69(6):1366-1379. doi:10.1016/j.pharep.2017.05.014
  10. Jacobs JP, Gupta A, Bhatt RR, et al. Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome. 2021;9(1):236. doi:10.1186/s40168-021-01188-6

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Reviewed May 2022