All Boards >> Irritable Bowel Syndrome Research Library

View all threads Posts     Flat     Threaded

Clinical Insights in IBS-C and Chronic Constipation
      12/08/05 12:37 PM

Reged: 12/09/02
Posts: 7795
Loc: Seattle, WA

Medscape Clinical Insights in IBS-C and Chronic Constipation: An Expert Interview With Philip S. Schoenfeld, MD, MSEd, MSc

Posted 11/08/2005

Editor's Note:
Irritable bowel syndrome (IBS), a functional gastrointestinal disorder characterized by the interplay of altered motility, abnormal visceral sensation, and psychosocial factors, is one of the most common reasons for referral to a gastroenterologist. Chronic constipation is one of the most frequent gastrointestinal symptoms in the United States, accounting for nearly 2.5-2.7 million physician visits and 39,000-90,000 hospitalizations per year in the United States.

Constipation may be stratified, with considerable overlap, into issues of stool consistency vs defecatory behavior. A fundamental challenge to the treating physician derives from the fact that the term "constipation" has different meanings for different individuals and is therefore often subjectively defined, depending largely on a patient's perception of alterations in his or her bowel function. Thus, it is essential that the clinician understand not only the symptom-based criteria for chronic constipation but also the myriad other complaints and descriptors that patients may use to define their problem.

Indeed, it is the overlap in symptoms reported by patients with IBS with a predominant bowel complaint of constipation (IBS-C) and chronic constipation that poses a challenge in differential diagnosis.

Medscape spoke with Philip S. Schoenfeld, MD, MSEd, MSc, Assistant Professor of Medicine, University of Michigan School of Medicine, Ann Arbor; Chief, Division of Gastroenterology, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, to explore the impact of these clinically important gastrointestinal conditions on both the healthcare industry and patient alike, as well as to discuss the current state of the field regarding the management of IBS-C and chronic constipation, as framed by data presented during the 2005 annual meeting of the American College of Gastroenterology.

Medscape: Given the variety of descriptors that patients with chronic constipation may use to define their problem, and the varied clinical presentations of IBS, what should be the clinician's approach to working up the patient with the symptom of chronic constipation and to differentiating between IBS-C and chronic constipation, defining each as "real medical conditions" warranting treatment?

Dr. Schoenfeld: In the absence of alarm symptoms (eg, hematochezia, weight loss ≥ 10 pounds, family history of colon cancer/inflammatory bowel disease), patients with symptoms of chronic constipation or IBS do not require invasive diagnostic testing before initiating therapy. Primary care physicians may obtain a complete blood cell count and a fecal occult blood test because these basic tests identify other alarm signs (eg, iron-deficiency anemia or occult gastrointestinal bleeding). However, patients with chronic constipation/IBS symptoms and healthy controls have a similar probability of having clinically important disorders (eg, hypothyroidism, colon cancer). There is one possible exception: celiac sprue may present with IBS symptoms (ie, abdominal discomfort associated with altered bowel habits). Depending on the prevalence of celiac sprue in the geographic area, primary care physicians and gastroenterologists may consider obtaining serologic tests for celiac sprue (ie, endomysial antibody and/or tissue transglutaminase antibody testing) in patients with IBS symptoms. Finally, all individuals 50 years of age and older should be offered a colonoscopy as part of routine colorectal cancer screening.

Chronic constipation and IBS-C are 2 syndromes that share many symptoms. Both conditions are characterized by infrequent bowel movements; a sense of incomplete evacuation; straining to pass stool; and passage of hard, pellet-like stools. However, the severity of bloating and abdominal discomfort differentiates IBS-C from chronic constipation. If a patient describes considerable abdominal discomfort or bloating with their constipation symptoms, then this patient should be diagnosed with IBS-C. Therefore, physicians should ensure that they specifically ask constipated patients about abdominal discomfort in order to differentiate IBS-C from chronic constipation. This is important because only tegaserod has demonstrated improvement in the multiple symptoms of IBS-C, whereas several therapies, including lactulose and psyllium, are effective at improving stool frequency and consistency in patients with constipation.[1]

Medscape: Given the uncertainty over what constitutes effective management for chronic constipation and the challenges in diagnosing and treating IBS-C, our therapeutic arsenal has continued to evolve, with the goal of providing alternative treatment options to help meet these growing needs. In this setting, 5-HT4 agonist therapy may offer an effective therapeutic alternative for these patients. What is the pathophysiologic rationale for targeting the serotonergic system in patients with chronic constipation and IBS-C?

Dr. Schoenfeld: IBS is an organic disorder, characterized by identifiable pathophysiologic changes, including alterations in interleukin (IL)-10/IL-12 ratios consistent with a proinflammatory state, defects in serotonin receptors, and abnormalities in visceral hypersensitivity.[1-3] In other words, IBS is not a "functional" disorder that can only be diagnosed after other organic disorders are ruled out with diagnostic tests. Although IBS is an organic disorder, we do not have a simple blood test or tissue test to make the diagnosis. Therefore, we must rely on symptom-based diagnoses as discussed previously.

Research regarding the pathophysiologic basis of IBS is a rapidly advancing field. Patients with IBS and patients with ulcerative colitis demonstrate defective serotonin receptors in enterochromaffin cells. This defect results in a decrease in the activity of serotonin, which is the primary neurotransmitter in the enteric nervous system. Thus, IBS patients suffer from a decreased level of activity in the enteric nervous system, which produces decreased smooth muscle motility and an increased sensitivity to mild distention in the colon (ie, visceral hypersensitivity). 5-HT4 receptor agonists, such as tegaserod, stimulate serotonin receptors in the enteric nervous system that are downstream from the enterochromaffin cell. In other words, these agents bypass the defective serotonin receptors and stimulate downstream receptors to "normalize" enteric nervous system activity. This stimulation increases colonic motility, which can provide relief of chronic constipation symptoms and IBS symptoms.[2,3]

Medscape: A study presented during the 70th Annual Meeting of the American College of Gastroenterology (ACG) looked at the long-term efficacy of the 5-HT4 receptor agonist tegaserod in maintaining symptom improvement in patients with chronic constipation. What can you tell us about this study and what were the key findings?

Dr. Schoenfeld: In this 13-month extension study, Shetzline and colleagues[4] followed chronic constipation patients who initially participated in a 12-week, placebo-controlled, double-blind randomized controlled trial (RCT) comparing tegaserod vs placebo. Abdominal distention, bloating, and bowel habits were assessed monthly. Those patients who responded to tegaserod in the initial RCT continued to demonstrate significant improvement compared with baseline for abdominal distention, bothersomeness of constipation, satisfaction with bowel habits, and global relief of constipation. All of these improvements were statistically significant. These data constitute the longest duration data on improvement in constipation symptoms with any therapy.

Medscape: During this year's meeting proceedings, Reilly and colleagues[5] presented the results of a trial conducted in women with IBS-C evaluating patients' overall satisfaction with initial and repeated use of tegaserod. What were the clinically important findings of this study, and what, in your opinion, are the implications for clinical practice?

Dr. Schoenfeld: Women with IBS-C were randomized to tegaserod 6 mg twice daily vs placebo in this double-blind randomized controlled trial. This was a unique trial because patients were asked whether the study medication was better than previously used medications and whether they would use the study medication in the future for treatment of their IBS symptoms. These questions were asked in addition to standard questions about satisfactory relief of abdominal discomfort, altered bowel habits, and global IBS symptoms. The authors demonstrated that patients using tegaserod experienced greater relief of abdominal discomfort, constipation, and global IBS symptoms compared with placebo. Furthermore, the patients (up to 76%) were significantly more likely to report that tegaserod was more effective than medications previously used (the authors did not provide a detailed list of "other medications" used by patients) for their IBS, and up to 85% stated that they would continue to use this agent for treatment of their IBS and/or recommend this treatment to fellow patients with IBS.

Medscape: Were there any other data presented during this year's meeting that would help put this information into clinical context? What's new on the therapeutic landscape?

Dr. Schoenfeld: Several new treatments for chronic constipation and IBS were discussed during this year's ACG meeting. Lubiprostone, which activates a chloride channel in the gastrointestinal tract, was examined in a double-blind, randomized placebo-controlled trial conducted in patients with chronic constipation.[6] In this 4-week trial, lubiprostone was found to be superior to placebo in terms of decreasing time to onset of first bowel movement and in increasing spontaneous bowel movement frequency. Patients treated with lubiprostone passed approximately 6 spontaneous bowel movements per week compared with placebo-treated patients who passed approximately 4 spontaneous bowel movements per week.

Additionally, in a double-blind randomized controlled trial involving female IBS patients, Quigley and colleagues[7] assessed the impact of a novel probiotic strain, Bifidobacteria infantis 35624, on bowel movement frequency. They found that the probiotic B infantis improved altered bowel habits in these patients with IBS. This is a particularly interesting avenue for further research because previous work reported by the same group of investigators demonstrated improvement in bloating in IBS patients using this probiotic.

American College of Gastroenterology Functional GI Disorder Task Force. An Evidence Based Approach to the Management of Irritable Bowel Syndrome in North America. Am J Gastroenterol. 2002;98:S1-S26.
Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004;126:1657-1664.
O'Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541-551.
Shetzline M, Dolker M, Bottoli I, et al. Patients with chronic constipation who respond to tegaserod after 4 weeks maintain symptom improvement for over 13 months. Am J Gastroenterol. 2005;100:S-339. [Abstract #927]
Reilly MC, Bracco A, McBurney CR, et al. IBS-C patients have greater treatment satisfaction with initial and repeated use of tegaserod. Am J Gastroenterol. 2005;100:S-339. [Abstract #926]
Johanson JF, Gargano MA, Holland PC, et al. Phase III study of lubiprostone, a chloride channel-2 (ClC2) activator for the treatment of constipation: safety and primary efficacy. Am J Gastroenterol. 2005;100:S-328. [Abstract #896]
Quigley EM, Whorwell PJ, Altringer J, et al. Probiotic use results in normalization of bowel movement frequency in IBS. Results froma clinical trial with the novel probiotic Bifidobacteria infantis 35624. Am J. Gastroenterol. 2005;100:S-326. [Abstract #888]

Funding Information

Supported by an independent educational grant from Novartis.

Philip S. Schoenfeld, MD, MSEd, MSc, Assistant Professor of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan; Chief, Division of Gastroenterology, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan

Philip S. Schoenfeld, MD, MSEd, MSc, has disclosed that he serves as a consultant to Novartis and GlaxoSmithKline. Dr. Schoenfeld has also disclosed that he serves on the speaker's bureau of Novartis.

Medscape Gastroenterology. 2005;7(2) 2005 Medscape

Heather is the Administrator of the IBS Message Boards. She is the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

Print     Remind Me     Notify Moderator    

Entire thread
* General IBS / Bowel Dysfunction
07/14/03 01:56 PM
* Top 25 recommendations for IBS from the American College of Gastroenterology
12/15/20 03:38 PM
* Postcolonoscopy Antibiotics Linked With IBS
06/02/20 02:14 PM
* Expanding Role of Fecal Microbiota Transplants: Hope or Hype?
12/30/19 03:03 PM
* Constipation in Older Adults Improved With Biofeedback
11/06/19 03:24 PM
* Patients with IBS Diarrhea, IBS Constipation, find their lives impacted in different ways
08/15/19 04:32 PM
* New, noninvasive test for bowel diseases
06/28/19 04:42 PM
* Oh, Poop! Study Links Pets to Higher IBS Risk for Owners
05/21/19 03:05 PM
* Microbiome science may deliver more effective, personalized treatment to children with IBS
04/23/19 03:23 PM
* Altered gut microbiota as a possible cause of IBS - Harmful bacteria increased in IBS, protective bacteria decreased.
04/09/19 01:59 PM
* 5 conditions that can cause uncontrolled bowel movements
02/28/19 03:01 PM
* Exercise boosts well-being by improving gut health
02/20/19 02:42 PM
* Scientists find that hundreds of gut bacteria are electric
09/19/18 01:06 PM
* Fecal transplantation may not improve IBS symptoms
08/22/18 02:03 PM
* Fecal Microbiota Transplant Relieves IBS With Predominant Bloating
07/25/18 12:46 PM
* April is IBS Awareness Month: 10 recent advances in research, diagnostics
04/16/18 02:05 PM
* Bacteria can trigger stomach cancer
08/25/17 04:11 PM
* Fecal microbiota transplantation improved symptoms and quality of life in patients with IBS
05/09/17 01:28 PM
* Autism symptoms improve after fecal transplant, small study finds
01/26/17 02:54 PM
* Microbiota and arthritis: correlations or cause?
02/19/16 01:09 PM
* Takeda, Enterome to collaborate on microbiome-based drugs for IBD, IBS, other GI disorders
01/11/16 03:21 PM
* Risk factors for IBS in military include stress, infectious gastroenteritis
01/11/16 03:19 PM
* Risk Factors ID'd for Fecal Transplant Failure
10/26/15 03:06 PM
* Blood Test Helps Some IBS Patients Get Firm Diagnosis
10/15/15 10:51 AM
* Differences in IBS patients' microbiota more significant in feces vs. mucosa
09/28/15 02:14 PM
* Higher reported cat dander sensitization rate may explain asthma prevalence in IBS patients
09/14/15 03:32 PM
* Picky Eaters Have Extra Helpings of Anxiety, Depression
08/05/15 03:42 PM
* Prediabetes Patients Have Fewer Gut Bugs
03/09/15 03:08 PM
* FDA approves Eclipse System for fecal incontinence in women
02/23/15 01:35 PM
* Fecal transplant leads to sudden obesity
02/23/15 01:24 PM
* New Criteria Would Double Fibromyalgia Cases
02/10/15 04:17 PM
* 2014 FDA approvals in gastroenterology
01/12/15 03:36 PM
* Colonoscopy prep affects gut bacteria
01/07/15 03:58 PM
* The Bile-IBS Link
12/15/14 03:18 PM
* Ineffective Pain Meds in IBS Patients Related to Immune System Changes
12/09/14 11:34 AM
* Volatile organic compounds accurate biomarkers for IBS in children
10/27/14 01:59 PM
* Researchers develop, validate eight GI symptom scales
10/07/14 02:17 PM
* Sleep Measures Can Help Predict Next-Day Symptoms in IBS Female Patients
09/17/14 02:27 PM
* Domestic violence may trigger irritable bowel syndrome
09/17/14 02:15 PM
* All IBS subtypes have similar symptom severity
09/05/14 03:50 PM
* Gut microbiome can diagnose colorectal cancer?
08/12/14 11:21 AM
* Sacral nerve stimulation does not help IBS
07/15/14 02:57 PM
* Small Study of IBS Patients Suggests Symptom Improvement with Fecal Microbiota Transplant
06/27/14 04:15 PM
* Vitamin D Role in Fecal Incontinence?
05/22/14 05:03 PM
* Colonic bile acid exposure influenced IBS symptoms
05/22/14 04:50 PM
* Good Vibration(s) for Constipation?
05/12/14 03:55 PM
* Can you give your spouse IBS?
04/22/14 02:12 PM
* Factors linked to chronic constipation
04/07/14 02:06 PM
* IBS patients' health perceptions focus on non-GI issues
04/07/14 01:35 PM
* Is IBS Funding a Joke?
01/17/14 11:53 AM
* Blood Test for IBS?
10/16/13 01:30 PM
* Gut microbes closely linked to proper immune function
09/17/13 02:09 PM
* More bugs in your gut = better health, lower body weight.
08/30/13 11:32 AM
* Top 10 Questions to Ask Your Doc about IBS
08/16/13 01:01 PM
* Had your gallbladder out? You may not have IBS.
08/16/13 01:01 PM
* IBS Quick Tip - Bloating Relief
08/16/13 01:00 PM
* Hot Summer Weather Affects IBS
08/16/13 12:58 PM
* Chronic Heartburn May Raise Odds for Throat Cancer
05/29/13 09:57 AM
* Support the Functional Gastrointestinal and Motility Disorders Research Enhancement Act
04/22/13 01:52 PM
* IBS increased risk for osteoporosis, related fractures
03/18/13 01:23 PM
* Weight Loss Better Than Drugs for Heartburn
02/13/13 10:42 AM
* Greater antibiotic use raises incidence of C. diff infections
10/31/12 11:35 AM
* No evidence supports colonic irrigation for IBS
06/15/12 03:11 PM
* Two Questions For Your Doctor Before A Colonoscopy
06/15/12 03:06 PM
* Dietary cleanses risky
06/15/12 01:22 PM
* Army of gut microbes keep us fit and healthy
06/15/12 01:19 PM
* Irritable Bowel Syndrome (IBS) and Bacteria in Gut
05/30/12 11:59 AM
* Can a Gut Check Boost Sleep, Sex and Brain Power?
05/02/12 10:27 AM
* April is IBS Awareness Month
04/23/12 01:47 PM
* Fecal matter, delivered by enema, helps heal in nine out of 10 cases
04/23/12 01:34 PM
* Too Many Americans Skipping Colon Cancer Screening
03/13/12 05:02 PM
* Chronic Heartburn a Growing Problem in U.S.
01/05/12 01:46 PM
* Fecal Transplants Show Promise for Gastrointestinal Ills
11/23/11 02:37 PM
* Stomach bug giardia linked to IBS and chronic fatigue syndrome
10/06/11 07:02 PM
* Gut analysis with smart pill could be new key to IBS treatment
10/06/11 06:58 PM
* Colon Cleansing Not Backed by Science and Can Be Dangerous
08/03/11 03:45 PM
* Gut Bacteria Falls Into Three Major Types
05/05/11 11:13 AM
* Stress May Alter Gut Bacteria and Hurt Immune System
04/06/11 04:31 PM
* Factors associated with co-morbid irritable bowel syndrome and chronic fatigue
02/10/11 10:21 AM
* Subtypes of Irritable Bowel Syndrome Based on Abdominal Pain/Discomfort Severity and Bowel Pattern
02/10/11 10:14 AM
* Irritable Bowel Syndrome Is Not In Your Head
09/24/10 02:42 PM
* Pain perception during colonoscopy higher in IBS patients than in non-IBS patients
07/21/10 03:52 PM
* Can Choir Singing Improve Irritable Bowel Syndrome?
06/24/10 01:48 PM
* Patients with IBS are NOT more likely to develop polyps, colon cancer
05/12/10 01:18 PM
* Rome Foundation Introduces Clinical Tool For Diagnosis Of Functional Gastrointestinal Disorders
04/12/10 11:40 AM
* Rotating Shift Workers At More Risk For Irritable Bowel Syndrome
04/12/10 11:39 AM
* Irritable bowel syndrome (IBS) does seem to run in families
04/02/10 11:14 AM
* IBS Does Not Increase Risk of Colon Cancer or IBD
03/12/10 11:30 AM
* Validation of Symptom-Based Diagnostic Criteria for Irritable Bowel Syndrome
03/11/10 01:53 PM
* Importance of early diagnosis in patients with irritable bowel syndrome
03/11/10 01:44 PM
* Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome
03/11/10 01:12 PM
* Constipation: a potential cause of pelvic floor damage?
09/29/09 12:10 PM
* Patients say they would give up 25% of their remaining life to be rid of IBS
08/28/09 01:21 PM
* IBS - it's the pain and the stigma
08/28/09 01:16 PM
* Wasington state retailers required to make bathrooms available to people with IBS and IBD
05/13/09 01:06 PM