by Dr. C.H. Weaver M.D. 4/1/2020
Cramping, abdominal pain, bloating, diarrhea and constipation. Do these symptoms sound familiar? If you experience any of them frequently enough to impact your quality of life, you may have IBS or irritable bowel syndrome. And if you have noticed that your stools are hard or lumpy, or that the number of days between bowel movements are increasing, you may have IBS-C or irritable bowel syndrome with constipation.1-3
One of 33 recognized adult functional gastrointestinal disorders (FGIDs), IBS is also the most prevalent4, with one-fifth of U.S. adults experiencing IBS symptoms. The odds of developing this chronic condition are increased if you are under fifty, have a family member who also has IBS, have a history of stressful or difficult life events or have a severe infection in your digestive tract. And if you’re a woman, your risk is even greater, since females are up to two times more likely than men to develop IBS.2, 5, 6
The good news is that while the symptoms of IBS in general can be painful and affect your overall quality of life, the disorder itself doesn’t lead to other health problems such as colorectal cancer or damage your digestive tract.6, 7 But the challenge in effectively treating IBS persists. Now a new medication specifically for those diagnosed with IBS-C shows promise in alleviating symptoms by addressing the symptoms in a unique way.
The Challenge of Treating IBS-C
Why is IBS-C so difficult to treat? In part, it’s because the disorder itself has no easily identifiable cause. And then there are the symptoms that can come and go without warning, making it hard to establish any kind of cause-and-effect. You ate X—was that what caused an IBS-C flare-up? Or you did Y and the next day your IBS-C is back—was that the reason?
Equally unreliable are the treatment results. Just because a certain medication worked for one person doesn’t mean it will work for you. Or for that matter, even if a treatment helped ease your bloating or resolved your constipation last month doesn’t mean it will continue to work this month or the next.
With a goal of seeking a solution that will help IBS-C patients, doctors often find themselves taking an “everything but the kitchen sink” approach. In addition to over-the-counter laxatives and prescription IBS-C treatments, healthcare providers may recommend taking probiotics or increasing fiber intake (either through the diet or as fiber supplements), although the latter could take up to 12 weeks for evidence that it’s working, according to the Mayo Clinic.10,13 Taking enteric-coated peppermint oil capsules may also improve IBS symptoms as can lifestyle changes that help reduce stress. 1,3,10 The use of laxatives is less than satisfactory. Laxatives may get things moving, so to speak but their impact is non consistent.
The U.S. Food and Drug Administration (FDA) has approved prescription medications for the treatment of IBS-C. For example, Lubiprostone increases the fluid your small intestine secretes which helps pass stool more easily reducing the risk of constipation. Linaclotide helps ease the symptoms of IBS-C by spurring more frequent bowel movements. They are however associated with problematic side effects including diarrhea and nausea. 25, 31, 32 Moreover three-quarters of patients using these treatments still have bouts of abdominal bloating/distension or abdominal discomfort and often require antispasmodic medication to help reduce muscle spasms. 8,12
Other patient complaints included hard, lumpy or pebble-like stools, gassiness, and an “incomplete emptying” sensation. 8,12 It’s no surprise that more than sixty percent of IBS-C clinical study participants aren’t happy with the results of their medication. This dissatisfaction with both the outcome and the medication side effects had led to more than two-thirds of prescription medication users discontinuing their treatment, and one-fifth electing to not use any treatment for their IBS-C symptoms at all.8
Patients with IBS-C are in need of new treatment options and Zelnorm (tegaserod) offers a new approach to treatment. Zelnorm is a selective serotonin-4 (5-HT4) receptor agonist, and the only IBS-C medicine that activates specific serotonin neuroreceptors in the gut to help regain healthy movement and ease abdominal pain. 26,28,29 Zelnorm stimulates the guts natural movement known as peristalsis causing the muscles that line the intestine to move together in wave-like contractions.15, 25 Since 5-HT4 agonists rely on natural stimuli to get things moving, they don’t cause spasms or what’s been called “perpetual uncontrolled propulsion.”30
The Enteric Nervous System, Serotonin and GI Function
To understand how Zelnorm works, you need to get acquainted with your gut’s “brain,” aka the enteric nervous system or ENS, and the relationship between serotonin and IBS-C. The enteric nervous system is composed of two thin layers of more than 100 million nerve cells that lines your GI tract from esophagus to rectum.16 These extensive neural circuits allow the ENS to monitor and send commands throughout the GI tract based on the information it receives from various sections. 17
Then there’s the serotonin connection, which researchers have linked to IBS. Serotonin is a neurotransmitter primarily found in the gut,18, 19 and when present at altered levels (too high or too low) can be linked to several chronic diseases, including irritable bowel syndrome (IBS).20 Too much serotonin is linked to IBS-D (diarrhea), while low levels can cause constipation, one of the symptoms of IBS-C.21
A Different Approach to IBS-C
Unlike other IBS-C medications, Zelnorm doesn’t address the constipation problem by increasing the fluid in the intestinal tract, but by communicating with your gut’s serotonin receptors who in turn help with relaxation and contraction of the muscles and decrease pain signaling.26, 34
The success of this approach was supported by three double-blind, placebo-controlled trials involving more than 2,400 women with at least a three-month history of IBS-C symptoms.15 Participants reported an improvement in abdominal pain and bloating, and an increase in the frequency of bowel movements in the first four weeks, with ZELNORM outperforming the placebo.21, 23, 25, 26 Among those patients in clinical trials who experienced diarrhea, 84% only had a single episode. 9, 23, 27
Following a complete safety review of clinical data from 29 controlled clinical trials and newly available sources of treatment outcome data by the FDA and an FDA-assembled Gastrointestinal Drugs Advisory Committee (GIDAC) 23, 24 Zelnorm received FDA approval in 2019 for use in adult women under 65 years of age with IBS-C.
Zelnorm is approved for use by individuals who have limited cardiovascular risk and is contraindicated for people with severe kidney problems or end-stage kidney disease, moderate or severe liver problems, women who are pregnant or plan to become pregnant or are breastfeeding or plan to breastfeed.23, 25
What can you expect if your doctor prescribes Zelnorm to treat your IBS-C? Patients have reported relief from constipation and abdominal pain as well as increased bowel movements—in some cases, as early as in the first week.33
While there’s no denying that IBS in general, and IBS-C in particular, is challenging to treat, by focusing on the serotonin connection to GI functioning, there’s real potential to reduce the symptoms and restore much-needed balance to the intestinal tract. And that’s an outcome that individuals with IBS-C will welcome.
- Diagnosis and treatment of irritable bowel syndrome with predominant constipation in the primary-care setting: focus on linaclotide. International Journal of General Medicine. Available at . Accessed January 19, 2020.
- Definition & Facts for Irritable Bowel Syndrome. The National Institute of Diabetes and Digestive and Kidney Diseases website. Available at . Accessed January 14, 2020.
- Irritable Bowel Syndrome. Mayo Clinic website. Available at . Accessed January 19, 2020.
- Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. Journal of Clinical Medicine. Available at . Accessed January 19, 2020.
- Irritable Bowel Syndrome. Office on Women’s Health website. Available at . Accessed January 19, 2020.
- Symptoms & Causes of Irritable Bowel Syndrome. The National Institute of Diabetes and Digestive and Kidney Diseases website. Available at . Accessed January 14, 2020.
- Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study. British Journal of Cancer. Available at . Accessed January 20, 2020.
- Better Understanding and Recognition of the Disconnects, Experiences, and Needs of Patients with Irritable Bowel Syndrome with Constipation (BURDEN IBS-C) Study: Results of an Online Questionnaire. Advances in Therapy volume 35, pages 967–980 (2018). Available at . Accessed January 17, 2020.
- Medline. Available at . Accessed January 20, 2020.
- Treatment for Irritable Bowel Syndrome. The National Institute of Diabetes and Digestive and Kidney Diseases website. Available at . Accessed January 14, 2020.
- The Use of Antidepressants in the Treatment of Irritable Bowel Syndrome and Other Functional GI Disorders. UNC School of Medicine — UNC Center for Functional GI & Motility Disorders. Available at . Accessed January 20, 2020.
- Antispasmodics. The National Institute of Diabetes and Digestive and Kidney Diseases website. Available at . Accessed January 14, 2020.
- Nonpharmacological approaches to management of functional gastrointestinal disorders — Where are we now?. Mayo Clinic website. Available at . Accessed January 19, 2020.
- Peppermint Oil. National Center for Complementary and Integrative Health (NCCIH). Available at . Accessed January 20, 2020.
- FDA approves reintroduction of Zelnorm for IBS-C in certain women. Helio. Available at . Accessed January 21, 2020.
- The Brain-Gut Connection. Johns Hopkins Medicine website. Available at: . Accessed January 17, 2020.
- Enteric nervous system. Scholarpedia website. Available at . Accessed January 22, 2020.
- Serotonin: What You Need to Know. Healthline. Available at . Accessed January 23, 2020.
- What is Serotonin?. Endocrine Society: Hormone Health Network website. Available at . Accessed January 23, 2020.
- Microbes Linked to the Production of Serotonin. Medical News - Archive 2015. Available at . Accessed January 17, 2020.
- Serotonin in the Gastrointestinal Tract. Current Opinion in Endocrinology, Diabetes and Obesity. Available at . Accessed January 19, 2020.
- Depressed Brain and Gut Mediated by Serotonin Levels. Genetic Engineering & Biotechnology News. Available at . Accessed January 22, 2020.
- FDA Approves the Reintroduction of Zelnorm (tegaserod) for Irritable Bowel Syndrome with Constipation (IBS-C) in Women Under 65. Drugs.com. Available at . Accessed January 22, 2020.
- Zelnorm Approval History. Drugs.com. Available at . Accessed January 22, 2020.
- ZELNORM patient brochure. Accessed January 19, 2020.
- IBS-C and Your Gut. MyZelnorm website. Available at . Accessed January 19, 2020.
- Zelnorm. RXList.com website. Available at . Accessed January 20, 2020.
- Serotonin Agonist. American Psychological Association website. Available at . Accessed January 20, 2020.
- FDA approves reintroduction of Zelnorm for IBS-C in certain women. Helio. Available at . Accessed January 23, 2020.
- The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders. Gastroenterology Journal. Available at [https://www.gastrojournal.org/article/S0016-5085(06)02436-X/abstract](https://www.gastrojournal.org/article/S0016-5085(06%2902436-X/abstract). Accessed January 19, 2020.
- How Effective Are Secretagogues for Irritable Bowel Syndrome With Constipation. Gastroenterology Journal. Available at [https://www.gastrojournal.org/article/S0016-5085(18)35214-4/fulltext](https://www.gastrojournal.org/article/S0016-5085(18%2935214-4/fulltext), Accessed January 29, 2020.
- Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis. Gastroenterology Journal. Available at , Accessed January 29, 2020.
- Relief With Zelnorm. MyZelnorm website. Available at . Accessed January 29, 2020.
- Rethink Your Treatment Options. MyZelnorm website. Available at . Accessed January 29, 2020.
- Side Effects. RX List. Available at . Accessed February 1, 2020.
- Warnings. RX List. Available at . Accessed February 1, 2020.