For many patients diagnosed with irritable bowel syndrome (IBS), lifestyle and dietary changes are the first steps recommended to manage their symptoms. This often includes exercising regularly, adjusting fiber intake, and trialing routine dietary advice. Patients may respond to a regular eating schedule, increasing fluid intake, limiting coffee and alcohol consumption, and food elimination diets such as a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet. Gut-directed psychological interventions such as relaxation therapy, cognitive behavioral therapy, psychotherapy, or hypnotherapy may also benefit patients with IBS. However, a subset of patients with IBS do not respond to nonpharmacological management alone and will require medications for symptom relief.

Medications that target specific bowel symptoms are traditionally used as first-line pharmacological management of IBS. These include antispasmodics to relieve abdominal pain and cramping, antidiarrheals to reduce the frequency of bowel movements and improve stool consistency in patients with diarrhea, laxatives to improve stool transit for patients with constipation, and opioid agonists, such as loperamide, to decrease intestinal motility. In patients who do not improve with laxatives, loperamide, or antispasmodics, antidepressants may relieve pain, modify the gut nervous system, and reduce stress.

Antispasmodics vary widely not only in their mechanisms of action and availability for use, but guidance from professional organizations also varies on the use of antispasmodics for the management of IBS. Although the National Institute for Health and Clinical Excellence (NICE) suggests the use of antispasmodics for managing IBS, the American College of Gastroenterology (ACG) suggests against the use of those antispasmodics currently available in the United States (including dicyclomine, hyoscyamine, and hyoscine) due to limited evidence for effectiveness in treating global IBS symptoms. The British Society of Gastroenterology (BSG) suggests that IBS symptoms may be effectively treated using certain antispasmodics, but warns of common adverse effects include visual disturbances, dizziness, and dry mouth.

Evidence and guidance concerning the use of laxatives in the treatment of patients with IBS and constipation (IBS-C) is similarly conflicting. NICE supports considering laxatives (except lactulose) to manage IBS, and BSG suggests that polyethylene glycol (PEG) may be an effective treatment for constipation in patients with IBS. However, ACG conditionally recommends against the use of PEG for global IBS symptom relief due to a lack of evidence for efficacy in relieving abdominal pain.

In patients with IBS and diarrhea (IBS-D), professional organizations generally support the use of the opioid agonist loperamide. However, despite that loperamide is associated with reduced diarrhea, side effects that can mimic IBS symptoms such as bloating, abdominal pain, and constipation are common.

More recently, multiple medications have received FDA approval for the targeted treatment of specific subtypes of IBS, expanding the options for pharmacological management. Since 2019, three new drugs have been approved by the FDA for the management of patients with IBS-D:

Eluxadoline, an opioid receptor antagonist, was FDA approved in 2020 and is generally supported by professional organizations based on the results of several randomized trials demonstrating benefit over placebo in improvement of both stool consistency and abdominal pain.

The antibiotic Rifaximin was approved by the FDA for IBS management in 2022 based on efficacy for improvement in overall symptoms, although BSG notes that its impact on abdominal pain may be limited.

Alosetron, a serotonin subtype 3 (5-HT3) antagonist, was granted FDA approval in 2019 for the management of severe IBS-D in female patients who have failed conventional therapies. However, due to concerns with the safety profile of Alosetron, a risk evaluation and mitigation strategy must be used while prescribing this medication, with a restricted prescribing dose. In places where Alosetron is not available, the 5-HT3 antagonist Ondansetron may be considered, but recent trials and meta-analyses did not show any benefit of this drug in the treatment of abdominal pain.

For the management of patients with IBS and constipation (IBS-C), five medications have been approved by the FDA since 2018. Two of these are indicated for the treatment of IBS-C in female patients specifically:

Tegaserod, a serotonin subtype 4 (5-HT4) agonist, was FDA approved in 2020 for the treatment of IBS-C in female patients under 65 years old. However, this medication is contraindicated in patients with a variety of conditions and risk factors, including cardiovascular risks, so it should be prescribed with caution.

Lubiprostone, a secretagogue that targets gut intraluminal ion channels, was FDA approved in 2021 for the treatment of IBS-C in female adults and its use is supported by both the ACG and BSG, based on the results from several randomized control trials showing effectiveness in improving overall IBS-C symptoms. 

Linaclotide and plecanatide, both guanylate cyclase-C agonists and secretagogues, were granted FDA approval in 2021 and 2018, respectively, for the treatment of IBS-C in adults. Their use is supported by multiple professional organizations for global IBS-C symptom relief, but despite high tolerability profiles, both have diarrhea as a common side effect.

Finally, tenapanor, also a secretagogue, was approved by the FDA in 2022 for the treatment of IBS-C, but diarrhea, which can be severe, is also commonly reported.

Of note, many of these newer medications are not available in all regions, and some have specific contraindications that should be reviewed carefully before use. For more information and a description of medications currently available for the management of IBS, see DynaMedex.

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