Irritable bowel syndrome (IBS) is not a new disorder, but physicians' understanding of its pathophysiology and treatment has greatly progressed over the years, said gastroenterologist Brian E. Lacy, MD, PhD.
“In the 1940s and 1950s, many health care providers thought that IBS developed due to anxiety or depression, and many patients were told that it was ‘all in your head,’” he said. “This led to IBS being called ‘nervous colitis.’”
In the past 20 years, research has shown that the gut microbiome, food, and genetics all play a key role in the development of IBS, said Dr. Lacy, a professor of medicine and consultant at the Mayo Clinic in Jacksonville, Fla. And now that more is known about the bidirectional communication between the brain and gut, IBS is considered a disorder of gut-brain interaction (DGBI), he noted. “We are getting away from the term ‘functional bowel disorders.’”
As the science around IBS has advanced, care is naturally following suit. Internal medicine physicians should work to address symptoms, often alongside other specialists and health care professionals, and be aware of the available evidence-based treatments, said Ekta Gupta, MD, an assistant professor of medicine at Johns Hopkins University in Baltimore and director of endoscopy for Johns Hopkins Gastroenterology and Hepatology in Columbia, Md.
“I feel strongly that the concerns by patients who present with possible IBS symptoms should not be dismissed or brushed off,” she said. “Most of the time, having a listening ear by any physician and having that empathy is a first step towards healing … and there are multiple newer ways by which we can effectively manage patients' symptoms.”
Experts outlined first-line treatments for IBS, as recommended by recent guidelines, and explained when (and how) to refer to gastroenterology or other specialty care.
Starting IBS treatment
To diagnose IBS, clinicians should take a thoughtful history, do a careful physical exam, use Rome IV criteria, and conduct limited diagnostic testing (complete blood count, C-reactive protein, and possibly celiac serologies and fecal calprotectin, depending on symptoms), said Dr. Lacy, who was lead author of the American College of Gastroenterology's (ACG) clinical guideline on the management of IBS, which was published in January 2021 by the American Journal of Gastroenterology.
“I believe the first step is to categorize patients into a mild, moderate, or severe IBS category, regardless of whether they have constipation-predominant symptoms, diarrhea-predominant, or mixed constipation [and] diarrhea,” Dr. Lacy said.
Treatment depends on the severity of IBS. About 40% of patients have mild symptoms, 35% have moderate symptoms, and 25% have severe symptoms, he noted.
Many patients with mild symptoms (present and bothersome, but not intrusive into work and personal life) do well with education, reassurance, making a positive diagnosis, and using diet, such as a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs), Dr. Lacy said. Lifestyle changes can also be helpful and include routine bathroom time to help with disordered bowel movements, exercise to reduce stress, and better sleep hygiene, he added.
For those with moderate IBS, who more frequently encounter symptoms that are more intense and have begun to affect work and personal life, “Follow those same steps, but medical therapy will be required,” he said, adding that patients with severe symptoms should also receive medical treatment, often in addition to psychological support. “These patients generally have significant psychological distress, and the assistance of a psychiatrist/therapist is often required.”
When considering treatments, the next key is to identify the IBS subtype, which is defined by the presence of characteristic symptoms. As defined by Rome IV criteria, the IBS subtypes include constipation-predominant (IBS-C; more than 25% of bowel movements with Bristol stool types 1 or 2), diarrhea-predominant (IBS-D; more than 25% of bowel movements with Bristol stool types 6 or 7), mixed bowel habits (IBS-M; more than 25% of each stool type), or unclassified IBS.
After identifying the subtype, “Focus on the most bothersome symptom,” Dr. Lacy said.
To help clinicians make medication decisions, the American Gastroenterological Association (AGA) released clinical practice guidelines on the pharmacological management of patients with IBS-C and IBS-D, which were published in July 2022 by Gastroenterology and update the AGA's previous recommendations from 2014. The ACG also offered treatment recommendations in its 2021 guideline.
For IBS-C, several FDA-approved medications are available. The ACG strongly recommended use of guanylate cyclase activators to treat global IBS-C symptoms, with a high quality of evidence.
The AGA's strongest recommendation is for linaclotide, a guanylate cyclase activator that has been available for several years. “This is the one agent in the guidelines for IBS-C that was given a strong recommendation with a high certainty of evidence, so in patients with IBS-C, the AGA recommends the use of linaclotide,” said Lin Chang, MD, lead author of the guideline and a professor of medicine in the Vatche and Tamar Manouklan Division of Digestive Diseases at the David Geffen School of Medicine at the University of California, Los Angeles, during an AGA webinar in July. The AGA also suggested the use of plecanatide, the second guanylate cyclase activator to be approved in 2017, with a moderate certainty of evidence.
Drs. Lacy and Gupta said they generally tend to first select linaclotide for IBS-C symptoms. “It was approved 10 years ago—that's a long track record of success,” Dr. Lacy said. “Three different doses are now available, although only one is technically approved for IBS-C.”
The ACG also strongly recommended use of chloride channel activators to treat global IBS-C symptoms, with a moderate quality of evidence. In this class, the AGA suggested use of lubiprostone, with a moderate certainty of evidence. It also suggested use of tenapanor, approved by the FDA in 2019, as well as tegaserod (although the latter is no longer available in the U.S. as of June 30). While the ACG suggested against using polyethylene glycol laxatives for IBS-C, the AGA made a conditional recommendation in favor, both with low certainty of evidence.
For global IBS-D symptoms, the ACG guideline strongly recommended rifaximin, with a moderate quality of evidence, while the AGA guideline for IBS-D made no strong recommendations for any of the available drugs.
As in its 2014 guideline, the AGA made a conditional recommendation with a moderate quality of evidence for rifaximin, suggesting use of the gut-selective antibiotic over no treatment. “It had overall beneficial effects with little side effects, we noted, although the cost of treatment may be high,” said Anthony Lembo, MD, lead author of the guideline, during an AGA webinar in July.
Since then, the TARGET 3 study found that repeat treatment with rifaximin is safe and effective in IBS-D patients with an initial response to the drug who develop symptoms, he noted. Thus, the AGA now suggests retreatment with rifaximin in such patients, a conditional recommendation with moderate-certainty evidence.
“For IBS-D, I might first reach for rifaximin, due to the very good safety profile (but ignoring the expense issue),” Dr. Lacy said. “If no benefit, then eluxadoline.”
Dr. Gupta said rifaximin is her personal favorite treatment for IBS-D. “There are studies to back it up, and also based on patients' feedback and the success that we've had in improving symptoms. … It is still expensive, but with rifaximin also finding a place in guidelines and FDA approval, it is becoming easier and easier access for patients—access meaning insurance covering the medication, so it is at minimal cost to patients,” she noted.
The ACG guideline suggested that mixed opioid agonists/antagonists, such as eluxadoline, be used to treat global IBS-D symptoms, and the AGA suggested the use of eluxadoline over no drug treatment, both with a moderate certainty of evidence. Of note, eluxadoline is contraindicated in patients without a gallbladder or those who drink more than three alcoholic beverages per day due to cases of sphincter of Oddi dysfunction and pancreatitis in clinical trials, said Dr. Lembo, a professor of medicine in the division of gastroenterology at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston.
The ACG conditionally recommended that alosetron be used in women with severe IBS-D symptoms who have not responded to conventional therapy, with a low quality of evidence, whereas the AGA suggested its use with moderate-certainty evidence. The AGA also suggested the use of loperamide despite very low quality of evidence. “This is based partly on the fact that the drug is known to be safe at recommended doses, it's widely available, and relatively inexpensive,” Dr. Lembo said.
Other IBS therapies
The guidelines also reviewed tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), gut-directed psychotherapies, and antispasmodics for all patients with IBS, regardless of Rome IV subtype.
While the ACG strongly recommended tricyclic antidepressants for global symptoms of IBS, with a moderate quality of evidence, the AGA's guidance was a conditional recommendation based on low-quality evidence. “We do know that these drugs can be associated with side effects, although the dosing that's typically used is low, somewhere between 10 and up to 75 mg/d, which is below the typically recommended dose for depression,” Dr. Lembo noted.
On the other hand, the AGA suggested against the use of SSRIs versus no drug treatment. “The overall quality of evidence across all critical outcomes for SSRIs was low, and overall there was no improvement in global relief or abdominal pain in IBS,” he said. However, “At times you may want to use this if you have someone with severe anxiety, where you feel that an SSRI may be beneficial for improving the anxiety, as well as perhaps some of the IBS symptoms.”
While the ACG conditionally recommended against the use of antispasmodics (e.g., dicyclomine, hyoscyamine, and hyoscine) for the treatment of global IBS symptoms, the AGA guideline suggested their use, including peppermint oil, in patients with IBS versus no drug treatment, with low-quality evidence. In a separate recommendation, the ACG suggested use of peppermint to provide relief of global IBS symptoms, with a low quality of evidence.
Antispasmodics, which help reduce smooth-muscle contractions, “are very beneficial in relieving day-to-day abdominal pain symptoms,” Dr. Gupta noted, adding that most peppermint oil is available over the counter.
When to refer?
Although internal medicine physicians can diagnose and manage patients with IBS on their own, they should take a collaborative approach in management with other specialists and health care professionals, said Dr. Gupta. She follows this approach herself; for example, she often refers patients with specific diet questions to a dietitian.
“I'm a gastroenterologist, so I'm not a nutritionist. … [They] have a greater knowledge about diet, and they can make it more fun and manageable,” Dr. Gupta said. More information about the role of diet in IBS was published in an AGA clinical practice update in March.
The ACG conditionally recommended a limited trial of a low-FODMAP diet in patients with IBS to improve global IBS symptoms, with a very low quality of evidence. The diet is a safe and reasonable first approach for patients with IBS, often providing benefits such as reduced gas and bloating and improved bowel habits, Dr. Lacy said.
The first step is to restrict diet by eliminating high-FODMAP foods, and then, if the patient notices a benefit, foods are slowly reintroduced and the diet is personalized with the help of a dietitian, he said. “If no benefit after four weeks, then the diet should be stopped, as this shows that foods are likely not a culprit in symptom generation.”
Internal medicine physicians should refer IBS patients interested in a low-FODMAP diet to a dietitian, said Dr. Lacy. “This diet can be tricky to adhere to,” he said. “Simply handing someone a sheet of paper with suggestions is not enough.”
While seeing a dietitian is preferred, patients may also choose to use the app sponsored by Monash University in Australia, which invented the diet. “There is a fee for the app, but all of the small fee—about $9—goes back into research,” Dr. Lacy said.
Dr. Gupta said she has heard good feedback from patients who use the app. “It's having that knowledge at your fingertips,” she said. “If you're in a restaurant or a grocery store, you will not be carrying a book.”
Fiber has also been shown to provide benefit, Dr. Lacy noted. The ACG guideline strongly suggested that soluble, but not insoluble, fiber be used to treat global IBS symptoms, with a moderate quality of evidence. “Most Americans are fiber deficient. Adding in soluble fiber is safe, easy, cheap … [but] I caution patients not to do this too quickly, as it may worsen bloating,” he said.
As for behavioral therapies, clinicians recognize their role in IBS more now than in the past, said William D. Chey, MD, FACP, a professor of medicine at the University of Michigan in Ann Arbor, during his talk on the future of GI at the Northern California Society for Clinical Gastroenterology annual symposium in June 2022. “I think anybody you talk to that's going through a GI fellowship at this point would believe that behavioral therapies are a really valuable tool in treating patients with DGBI and other GI disorders, whereas that wasn't even on the radar screen when I was going through fellowship 30 years ago,” he said.
Internal medicine physicians should refer patients with IBS and substantial psychological distress (e.g., anxiety, depression, somatoform disturbance) to a psychiatrist, Dr. Lacy said. “GI symptoms will continue until the psychological distress is brought under better control—all part of the brain-gut axis,” he said. In addition, the ACG guideline suggested that gut-directed psychotherapies be used to treat global IBS symptoms, with a very low quality of evidence.
Patients should be referred to a behavioral therapist for cognitive behavioral therapy (CBT) if they are keen on the idea of learning new strategies to improve chronic symptoms, Dr. Lacy added. “CBT can be very useful, but patients need to be receptive to this.”
Finally, Dr. Lacy said patients should be referred to GI for three reasons: 1) if there are warning signs present (e.g., unexplained anemia, bleeding from the GI tract, concern over possible inflammatory bowel disease with need for colonoscopy to confirm), 2) for age-appropriate colorectal cancer screening, and 3) if they have persistent IBS symptoms that have not responded to what the primary care physician (PCP) considered reasonable empiric therapy.
A key teaching point is that if a referral is made to a gastroenterologist, the consultation note should be specific about what is wanted, he said. For example, a specific note may say, “Persistent IBS symptoms. Please evaluate the patient to consider the diagnosis and review/initiate new treatments.”
“Too many times, referrals go to a GI provider for ‘IBS and diarrhea symptoms,’ and then the patient is scheduled just for a colonoscopy (which is usually normal), and then no follow-up is arranged, and the patient returns back to the PCP with a normal colonoscopy report,” Dr. Lacy said. “This isn't efficient and is certainly frustrating for the patient and the referring provider.”
Of importance, referring to a gastroenterologist doesn't mean deferring management entirely, Dr. Gupta said. “[The gastroenterologist] can start the management, have them in cruise control mode, and then [the patient] may not even need to follow up with GI as much, and then the [PCP] can just keep them in the cruise control mode,” she said.