Earlier this month, guideline authors Shahnaz Sultan, MD, MHSc, AGAF, Lin Chang, MD, AGAF, and Anthony Lembo, MD, AGAF, hosted a Gastro Bites open discussion about AGA’s clinical guideline on the pharmacological management of irritable bowel syndrome with constipation (IBS-C).
During the chat, they discussed key takeaways from the guidelines such as when to rely on old drugs approved by the FDA and when to use over-the-counter drugs.
Here are a few of our top questions from the webinar:
Tegaserod (Zelnorm®) was originally approved in 2002 for the treatment of IBS-C in women. The drug’s manufacturer (Novartis) voluntarily pulled from the U.S. market in 2007 due to concerns of cardiac-related side effects. In 2019 following a safety review the FDA re-approved tegaserod 6 mg twice a day that included review of data in women under the age of 65 without cardiovascular risks (i.e,. history of myocardial infarction stroke, TIA or angina). Recently, it was reported that the tegaserod is being withdrawn due to “business reasons.” Zelnorm® (tegaserod) will remain available in the US marketplace until existing supplies have been depleted. See FAQs about Zelnorm.
Stimulant laxatives (e.g., senna, bisacodyl) have been studied in randomized controlled trials to a limited degree in patients with chronic idiopathic constipation and appear to be effective at improving stool frequency, consistency, and incomplete evacuation. Stimulant laxative has not been studied in IBS-C and therefore there is no evidence that stimulant laxatives will reduce abdominal pain in IBS-C. However, in patients with IBS-C without significant abdominal pain in whom constipation is not responsive to available treatments shown to relieve IBS-C symptoms, a laxative can be considered. Osmotic laxatives are generally recommended initially as they tend to cause fewer abdominal symptoms but if ineffective a stimulant laxative can be considered.
IBS-C and CIC exist along a spectrum with significant symptom overlap and many patients migrate between these diagnoses over time. IBS-C is characterized by the presence of abdominal pain associated with constipation, while CIC is characterized by constipation without predominant pain. IBS-C has been shown to be associated with visceral hypersensitivity and dysregulated colonic motility although most patients have normal colonic transit times. CIC is subtyped into slow transit constipation or normal transit constipation with or without a defecatory disorder. Normal transit constipation has not been studied well but can potentially have a shared pathophysiology with IBS-C.
The FDA approved dose of linaclotide for IBS-C is 290 mcg daily, however, there is evidence that the 145-mcg daily dose can also reduce abdominal pain. We generally recommend using the 290-mcg dose in IBS-C, but if there are concerns about the side effect of diarrhea or if diarrhea occurs or persists at 290-mcg it is reasonable to consider the lower doses (i.e, 72-mcg or 145-mcg daily).
Antispasmodics were evaluated in the AGA guidelines published in 2014 and this information was also included in both the updated IBS-C and IBS-D guidelines. Antispasmodics have not been specifically studied in IBS-C but it is reasonable to use these medications cautiously in IBS-C due to an increased risk of constipation with regular use. It can be used on an as needed basis in IBS-C to minimize the risk of constipation.
Desipramine can be considered for pain predominant symptoms in patients with IBS-C. Desipramine is a better choice than amitriptyline to avoid some anticholinergic effects (which can be constipating) in patients with IBS-C. If constipation worsens, one can increase the constipation treatment.
In patients with typical IBS symptoms who do not have alarm features (e.g., bloody stools, unintentional weight loss, family history of colon cancer, IBD or celiac disease), a colonoscopy is generally not indicated. A colonoscopy should be recommended for routine colorectal screening as recommended to the general population.
General dietary recommendations for individuals with IBS include eating regular meals that include typical portions and not overeat, reduce intake of alcohol, caffeine, spicy foods, dietary sugars, excess amount of fructose, and fats. Additional foods that consistently trigger IBS symptoms should be avoided. For IBS-C, soluble fiber supplementation is generally recommended. More information is available in the AGA Clinical Practice Update on Diet in IBS which was published in Gastroenterology earlier this year.
Duration of treatment with medications that are specifically treating psychiatric symptoms should be determined on an individual basis. Neuromodulators that are being used to treat IBS symptoms are usually continued until symptoms are under good control for at least 6-12 months and then can be tapered off. However, some patients with IBS will need to continue neuromodulators for a longer period to experience symptom relief and avoid symptom flares.
Colchicine can help reduce constipation symptoms but has not been studied well in IBS and has not been shown to reduce abdominal pain, so it is likely to have limited efficacy in IBS-C.
