DR. CASH: Irritable bowel syndrome (IBS) is a common clinical condition that is encountered in multiple practice settings. Traditionally, IBS has been thought to have 3 distinct clinical presentations: IBS with constipation, IBS with diarrhea, and IBS with a mixed bowel habit pattern.
Over the past several decades, our understanding of the function of the gastrointestinal (GI) tract, especially with regard to those controlled by the enteric nervous system, has increased dramatically. This increase in knowledge has been accompanied by an enhanced appreciation of the importance of the various functional GI disorders in terms of the pathophysiology and societal impact.
IBS is a prototypical functional GI disorder that affects more than 15% of the population1 and has been gaining increasing awareness in the press and media over the past decade. This period has also witnessed several diagnostic and therapeutic clinical trials with a more dichotomous approach to IBS, which separates the clinical presentations into IBS with constipation and IBS without constipation.
Investigators and clinicians alike have realized that the pragmatic approach, using the presence or absence of constipation as a symptom of IBS, may lend itself to the subsequent evaluation and management of the disorder. Additional insights of the role of inflammation and food intolerance have fundamentally altered the approach to IBS and its associated symptoms. Likewise, the development of targeted therapies for patients who have IBS with constipation and IBS without constipation has increased the number of options available to clinicians as well as the improved quality of life of patients.
My name is Brooks Cash, and I am Professor of Medicine at the Uniformed Services University of the Health Sciences, as well as a gastroenterologist and Deputy Commander for Medical Services at the Walter Reed National Military Medical Center in Bethesda, Maryland. I am joined by 3 world-renowned experts in the field of functional GI disorders and IBS in particular: Drs. Lin Chang, Lucinda Harris, and Brian Lacy.
Welcome everybody, and thank you for taking the time to discuss up-and-coming topics surrounding nonconstipation IBS. Why don’t you take a moment to introduce yourselves?
DR. CHANG: I’m Lin Chang. I’m a gastroenterologist and Professor of Medicine in the Division of Digestive Diseases at the David Geffen School of Medicine at UCLA.
DR. HARRIS: I’m Lucinda Harris. I am co-director of motility in the Division of Gastroenterology at the Mayo Clinic in Scottsdale and Associate Professor of Medicine in the Mayo School of Medicine.
DR. LACY: Hi, I’m Brian Lacy. I’m Professor of Medicine at the Geisel School of Medicine at Dartmouth and director of the GI Motility Laboratory at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.
DR. CASH: Let’s start with a general overview. Dr. Lacy, will you describe the epidemiology and impact of nonconstipation IBS?
DR. LACY: When I think about the epidemiology of IBS, I like to break it down into both prevalence and incidence. The prevalence of IBS has been actively studied over the years, and it varies depending on how IBS was defined and where the study was performed.
In general, we consider IBS one of the most prevalent functional bowel disorders and certainly one of the most well studied ones as well. Some of the earlier criteria, as you know, involved the Manning criteria.2 These were a little bit more generous and less restrictive than the recent Rome criteria, but, in general, if we were to use a comprehensive review published in 2002 by Saito and colleagues3 from the Mayo Clinic, the prevalence of IBS in North America ranges from approximately 3% to 20%, and most studies quote the prevalence of IBS in about the 12% to 15% range.4–6 The incidence of IBS is slightly more difficult to calculate. That being said, the incidence ranges from about 200 to 400 in 100,000 people, or about 1% to 2% per year in the United States.6,7
DR. CASH: What about the impact in terms of quality of life and economics?
DR. LACY: In terms of the impact of IBS, I think there are a couple of different ways to analyze it. The first is to point out its prevalence, knowing that in primary care, about 10% to 15% of primary care visits are for IBS symptoms, and in the GI referral community, that number may be as high as 40% or 50%.8,9 We know that about two-thirds of those visits are for nonconstipated IBS patients.
Secondly, we can look at the impact on patients, and often, we measure that in terms of quality of life. We know that quality of life of patients with IBS is reduced similar to the case of patients with longstanding diabetes, and in terms of the physical score, it’s lower than that in patients with chronic acid reflux disease and even depression (using the SF-36). We also know from one study that IBS has been shown to increase the risk of suicide, and I think this points out how greatly this affects patients.10-12
Lastly, we can look at the economic impact of IBS. Again, we can either measure that in terms of the direct cost to patients or society. We know that this is one of the most common reasons for patients to skip school or work. We know that healthcare costs for patients with IBS are approximately 50% higher than that for age- and sex-matched controls without IBS.13-15
When we think about the impact on society, including lost healthcare costs, lost productivity, or medication use and procedures, IBS accounts for, on an average, about $20 billion to $30 billion per year of medical costs in the United States.14–17
DR. CHANG: The etiology of IBS is not really well understood, and I think the main issue is that it’s a multifactorial condition, and the clinical presentation can be very heterogeneous. That’s what makes it difficult to understand and makes the cause difficult to identify in each individual because the studies do not necessarily yield consistent results.
Now, it’s generally well accepted that IBS is due to an alteration in brain-gut communication or brain-gut interactions, and that leads to changes in GI motility, sensation, and secretion and increases the perception that the patient has of pain and other GI symptoms.
There are certain vulnerability factors that increase the risk of developing IBS, including genetic predisposition, because we know that IBS runs in families, and there seems to be some genetic component, although it’s still not very well understood. There’s also evidence that chronic stress early in life, or even as an adult, can increase the risk for developing IBS in addition to other chronic pain syndromes.
Then, there seems to be a trigger, which could be, for example, infection, with post-infectious IBS; that’s when a patient develops IBS after gastroenteritis, surgery, or a psychological stressor that’s more chronic and sustained. The patients could also develop symptoms of IBS that can wax and wane or can be chronic. IBS can vary in symptom presentation. Even after the trigger has passed, ie, the infection has cleared or the stressor is gone, the symptoms themselves can perpetuate the condition because of the possibility of symptom-associated anxiety, which would be very normal in patients with very bothersome symptoms.
There are also certain foods that may not really cause the onset of the IBS—unless it’s due to food poisoning—but can trigger the symptoms. There may also be some food intolerances or certain types of foods—such as fatty foods—or larger meals that don’t tend to sit well with patients.
Proposed mechanisms that may result in changes in GI function such as disturbed gut motility, secretion, and sensation and ultimately in the development of IBS symptoms include alterations in neuroimmune and neuroendocrine responses, intestinal permeability, central nervous system modulation of visceral stimuli and sensations, and serotonin signaling, and dysbiosis within the GI tract.18-22
DR. CASH: Dr. Chang, there are also other somatic comorbidities that patients with IBS often have. Can you tell us about those comorbidities, as well as the medical resource utilization that we might see in patients with IBS and those comorbidities? And finally, is it possible that there’s a shared pathophysiology with other somatic complaints or syndromes?
DR. CHANG: A number of studies have looked at the comorbidity of IBS with other functional somatic syndromes. I’m talking more about functional diseases. There is also evidence of IBS coexisting with gastroesophageal reflux disease or inflammatory bowel disease, but much of the literature on comorbidity with IBS is with other existing chronic pain syndromes or chronic somatic syndromes such as fibromyalgia, interstitial cystitis, temporomandibular joint disorder, migraine headaches, and chronic fatigue syndrome.
There are studies that look at the prevalence of these conditions in IBS, and there are studies that evaluate the prevalence of IBS in these conditions. It’s usually about 30% or a subgroup of IBS patients who have these other conditions.23 IBS and these other conditions are more prevalent in women.24
When you look at healthcare utilization—healthcare visits—what’s interesting is that studies show that IBS patients have a greater number of healthcare visits for GI symptoms than individuals without IBS. But many of their healthcare visits also are for non-GI complaints because many IBS patients report non-GI symptoms. Fatigue is one of the more common symptoms, and headaches or muscle aches are also common.
Sometimes, these symptom presentations don’t actually meet diagnostic criteria for other conditions such as migraine headaches, fibromyalgia, painful bladder syndrome, or interstitial cystitis. Interestingly, many IBS patients actually seek health care for those visits. In fact, when you look at the healthcare costs, there are more related costs due to diagnostic testing or medication or healthcare visits for non-GI complaints than there are for GI complaints. But for both types, the cost is higher than that for individuals without IBS.
I recently reviewed the literature on pathophysiologic mechanisms for IBS and other comorbidities, including functional dyspepsia, and there are a number of mechanisms that have been studied in IBS as well as these other conditions.23
Many abnormalities are very similar in IBS and the comorbid conditions. There’s evidence of increased pain perception and altered brain activation patterns in IBS and of these other conditions including fibromyalgia and temporomandibular joint disorder. The findings are very similar, and some of these brain areas that are abnormally activated are associated with either enhanced emotional arousal or altered pain processing.
There’s also evidence of immune changes such as increased numbers of mast cells, particularly in chronic fatigue syndrome and interstitial cystitis, and in some of the studies in functional dyspepsia and IBS. There’s also evidence of genetic factors and certain genetic polymorphisms that are associated with an increased prevalence of IBS or other chronic pain conditions.
Several different mechanisms appear to be shared among these different conditions.
DR. CASH: Dr. Harris, many consider the diagnosis of nonconstipation IBS one of exclusion, while others feel that the Rome criteria are sufficient to make the diagnosis. We heard Dr. Lacy refer to the Rome criteria earlier. What are the Rome criteria, and how valid are they in terms of making the diagnosis of IBS and in particular nonconstipation IBS?
DR. HARRIS: The Rome committee is a group of gastroenterologists that had met since 1997 to decide the diagnostic criteria of IBS, as well as other functional disorders. We are currently using the Rome III criteria,25 and they define IBS as recurrent abdominal pain or discomfort that occurs at least 3 days per months in the last 3 months and is associated with 2 or more of the following criteria: (1) the abdominal pain or discomfort improves with defecation, (2) the onset of symptoms is associated with a change in form of stool, and (3) the onset of symptoms is associated with a change in frequency of stool. Also, the symptom onset should be present for at least 6 months prior to diagnosis.
They have also further defined the criteria into IBS subtypes according to stool form so that IBS with constipation indicates that you have hard or lumpy stools ≥25% of the time and diarrhea (loose or mushy stools) <25% of the time. IBS with diarrhea means the stools are loose or mushy >25% of the time and hard or lumpy <25% of the time. Mixed type IBS is defined as hard and lumpy stools ≥25% of the time and loose or watery stools >25% of the time.25
Finally, there is IBS that can’t be subtyped, called IBS unsubtyped. These are people who we can’t be subtyped because they have insufficient abnormalities of stool subtype to meet the criteria above. But most patients, I think, when you speak to them, can give you an idea of how their bowel movements are and you can easily subtype them.
The other important factor in using the criteria is to make sure that there are no alarm symptoms such as age > 50 years during the onset of the symptoms, blood in the stool, nocturnal symptoms, unintentional weight loss, or a dramatic change in the pattern of symptoms. However, it is important to realize that the stool pattern can change.
It’s also important to make sure that there is no family history of organic GI diseases such as colon cancer, inflammatory bowel disease, or celiac disease, and that there’s no recent history of antibiotic intake.
If you use the red flag symptoms and look at the patient’s history of symptoms, a clinical diagnosis can be made.
DR. CASH: Dr. Lacy, some would suggest a role for diagnostic testing such as colonoscopy and celiac disease testing in nonconstipation IBS. What’s your opinion on that?
DR. LACY: Let’s tackle the easy one first, and I think that’s the role of colonoscopy. Several studies have pointed out that if patients meet Rome III criteria in the absence of warning signs, the utility of a colonoscopy would be very, very low.
We all agree that if the patient is older than 50 years, and ≥45 years for African Americans, even if there are signs of IBS and you’re pretty confident about the diagnosis, a colonoscopy is still required for screening purposes.
The utility of a colonoscopy in a younger patient—younger than 45 years—with classic symptoms of IBS in the absence of warning signs is extremely low, and I don’t generally recommend that.
One caveat, of course, is that as clinicians, we’re always double-checking to make sure that our diagnosis is correct. We review the patient, see them in follow-up, and make sure that our treatments are appropriate in helping the patients. But if things aren’t making sense, and if the patients aren’t responding, we’ll always go back and question whether the diagnosis was correct, realizing that in some patients with nonconstipated IBS, what appears to be IBS might actually be microscopic colitis, including lymphocytic colitis or collagenous colitis, and celiac disease.
That’s a nice segue, and I think testing for celiac disease is really quite controversial. We know from the study published in Lancet in 2001 by Sanders and colleagues26 that patients with IBS were apparently 5 to 10 times more likely to have celiac disease than those who did not have the disease, and there was a real level of enthusiasm to test nearly all patients with IBS to look for celiac disease.
We also know from the American College of Gastroenterology (ACG) guidelines27 published in 2009 that for patients with diarrhea-predominant IBS or mixed IBS, meaning the nonconstipated IBS patterns, testing for celiac disease is recommended. Keep in mind, of course, that the prevalence in the United States is estimated at about 1%. That being said, I think the best recent investigations were the multicenter trials involving Bethesda Naval and Michigan.28 This multicenter trial involved nearly 500 patients with nonconstipated IBS and nearly the same number of healthy controls who were admitted for routine colonoscopies, and the prevalence of celiac disease was virtually identical. It was 0.41% for IBS patients and 0.44% for controls. Thus, I don’t routinely recommend testing for celiac disease, although if someone has nonconstipated IBS symptoms and they don’t respond to what I think is appropriate initial empiric therapy, at some point, I may check them.
DR. CASH: So, Drs. Harris and Chang, what’s your take on the celiac question and should we be testing for celiac disease in patients with symptoms consistent with nonconstipation IBS?
DR. HARRIS: I find that in patients in whom bloating is a disproportionate symptom, it might be worthwhile to check for celiac disease and review the family history. I think we’ll get into this discussion a little more detail when we discuss the diet, but we also have to think about gluten sensitivity. It’s become more challenging to sort out who truly has celiac disease and who may have gluten sensitivity, and I think those are important considerations.
DR. CHANG: I agree. At this point, the evidence suggests that we should still screen for celiac disease because it is cost effective, since the treatment is so different from that for IBS.
I think for microscopic colitis as well, it would be nice to do a similar cost analysis to determine whether we should be screening for it more than we do because it’s actually fairly prevalent in the population of IBS patients with diarrhea, particularly in middle-aged women, as Brooks’ study demonstrated.29
DR. HARRIS: The prevalence in the Western world is estimated to be 1 in 132 patients.30
That’s a fairly common occurrence for a disorder, so I think the jury is still out. A study previously suggested that celiac disease is more common in IBS patients, and one study suggested that it isn’t so.27,28,31–33 I think that that the decision to screen or not to screen is not clear yet.
DR. CASH: Yes, it’s still a very controversial issue. Dr. Chang, once the diagnosis has been made, what is the natural history of nonconstipation IBS in terms of surgery rates or the change in diagnosis, perhaps even the risk of developing other disease, which seems to be a common concern of our patients?
DR. CHANG: There was one study that evaluated the natural history of IBS many years ago.34 It reviewed multiple other studies where they followed patients from 6 months to 6 years after the original IBS diagnosis, and they found—consistent with the data that you and others have presented—that the prevalence of determining an alternative diagnosis to IBS is very small.35 It’s about 2% or slightly more than that.
Up to 50% of patients will actually have unchanged symptoms over the years. About 2% to 18% will have worse symptoms.34
If you follow-up the IBS symptoms over time, about a quarter to a third of patients will actually become symptom-free. And we know from post-infectious IBS longitudinal data that the prevalence of IBS declines over time.
In general—and this is something that I tell my patients—the symptoms usually fluctuate over time and much of what we do to treat or manage the symptoms can help to alleviate them to a certain extent. But even when the patients are working hard to manage their symptoms, they can still have symptom flares, although they may be less frequent or milder, and that’s just part of the natural history.
For the bowel habit subtypes, studies have shown that if you follow-up patients, over time, their subtype of IBS can actually change. One study by Doug Drossman and colleagues36 followed IBS patients for over 1 year. They evaluated the symptoms every 3 months in that 1 year and found that 75% of IBS patients actually had a change in their bowel habit subtype over the 1 year.
You would typically see the IBS constipation and the mixed IBS interchanging from one another, and the mixed IBS would also interchange with the IBS with diarrhea. It was less frequent for an IBS with diarrhea to change into an IBS with constipation.
DR. CASH: Certainly, the changing clinical picture of IBS is going to make the evaluation and management of those patients more challenging as well.
Let’s shift over to the topic of treatment. Dr. Harris, you mentioned a few moments ago the role of gluten and perhaps gluten sensitivity. So what role, if any, does diet play in the treatment of nonconstipation IBS?
DR. HARRIS: I think that diet is probably the forgotten factor. Patients have, for years, been telling us that when they eat certain foods, they seem to experience more severe symptoms. They tell us that onions, garlic, fatty, and richer meals cause the symptoms to appear. In fact, Albena Halpert did a study37 that looked at factors in diet that have helped patients, and patients reported that if they ate smaller or less fatty meals or avoid lactose, their IBS symptoms improved.
So, lactose intolerance is a fairly common symptom in the population, in general, and the 2009 ACG guidelines quote a study that showed that the prevalence in the population is about 25%, whereas in the IBS patient population, it’s somewhat higher, around 35% to 38%.38
Patients find that when they avoid lactose, sometimes, there is an improvement in their symptoms of bloating and diarrhea.
In practice, I’ve found that perhaps the symptoms may not persistently improve, but patients do tend to feel better. Besides lactose, I think that consuming smaller meals, more frequent meals, and less fatty meals are also helpful for patients.
Recently, many researchers have been interested in both gluten sensitivity and FODMAPS, which stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, and these are essentially a group of carbohydrates in the diet that can cause GI symptoms, particularly diarrhea and bloating.
There is a review on FODMAPS and food intolerances by Barrett and Gibson in the July 2012 issue of Therapeutic Advances in Gastroenterology,39 as well as one from 2011 called Food: The Forgotten Factor by Dr. Eswaran in the Gastroenterology Clinics of North America.40 So, I would refer people to those reviews.
Essentially, there seems to be a group of patients who have carbohydrate intolerance. Fructose breath testing can help screen some of those patients, but by no means is it a definitive test for intolerance to carbohydrates.
Gluten is one of those carbohydrates. Essentially, gluten is a fructan, and when people go on a low-FODMAP diet, they inadvertently decrease gluten in their diet, although I think there is a subset of patients who also have sensitivity to wheat that’s different from a food allergy.
So, I think we need to get a better understanding of carbohydrates in the diet because in some patients, they seem to play a role in their symptoms.
DR. CASH: It certainly seems like an easy place to start for our patients as well.
DR. HARRIS: I would urge you to first test patients for celiac disease before you put them on a fructose-restricted diet, because once you reduce gluten in the diet, you may decrease your ability to diagnose celiac disease. I think that is an important consideration, and 10% of patients who have negative celiac disease serology can still have celiac disease even with negative blood tests.41
DR. CASH: Dr. Chang, it seems like patients and practitioners want to use agents such as probiotics for a myriad of conditions these days. Are there any data that support the use of probiotics in patients with nonconstipation IBS, and, if so, what are the thoughts with regards to how these agents might work?
DR. CHANG: There have actually been a number of studies evaluating the efficacy of probiotics in IBS patients; however, most studies haven’t really focused on a particular bowel habit. There is at least one study where they evaluated IBS with constipation.42,43
Although there are a number of probiotic studies, most of them are not of high quality. The one probiotic that has been examined in high-quality studies—two different studies—was Bifidobacterium infantis, and this probiotic has been shown to reduce IBS symptoms.44,45
In one study where they evaluated the medication in caplet form, the improvement in symptoms was seen at 4 weeks.45
So one take-home message from that study is that you’d want to keep the patient on probiotics for at least a month to determine whether it’s really efficacious.
The other probiotic that has been studied for IBS and bloating and gas-related symptoms is Bifidobacterium lactis or animalis (it has different names), and this probiotic is present in yogurt available in grocery stores. That has been shown to have some efficacy in decreasing IBS symptoms. But there are several other probiotics that have been shown (albeit not in high-quality studies) to have efficacy in IBS.
There are a number of mechanisms of action that probiotics can help for both digestive health and GI disease, and these include modulating the signals in the gut and affecting immune modulation. By ingesting these probiotics, you may change the composition of the bacterial flora in the gut, which can yield beneficial effects.
There’s also evidence that probiotics maintain the barrier function of the intestinal lining that might be beneficial in IBS, because there is some evidence that IBS patients—or at least a subgroup of IBS patients—have increased intestinal permeability, which may play a role in symptom presentation.
DR. CASH: Dr. Lacy, what medications have evidence to support their use in nonconstipation IBS, and is there a tiered approach to their use?
DR. LACY: I think a good approach is to remind ourselves that we can’t cure IBS, and that our goal is to improve patients’ symptoms. With that in mind, when I see nonconstipated IBS patients, often, I start treatment with an antidiarrheal agent, which might include Imodium or Lomotil. These may improve diarrhea, but they won’t help pain or bloating, which are the most common reasons patients come to see a gastroenterologist.
I frequently use alosetron. This is the only Food and Drug Administration (FDA)-approved medication for women with IBS and diarrhea symptoms. It’s been shown to be safe and effective. I may use a bile acid-binding agent such as cholestyramine or colestipol or colesevelam, although there are very limited data to support their use. It doesn’t mean they don’t work; we just don’t have a lot of data on them.
There are limited data showing that smooth muscle anti-spasmodics, mostly due to their anticholinergic activity, may slow down the action of the GI tract and improve symptoms of pain. Some providers use low-dose tricyclic antidepressants to both slow the GI tract and improve pain. There are also limited data on clonidine and a small study evaluating the use of dextofisopam.
But that’s our armamentarium right now, and I think the art of this job is to try to find the right medication for the right patient while minimizing the side effects.
DR. CASH: Along those lines, Dr. Lacy, there were recently some data with regard to antibiotics for nonconstipation IBS and bloating. Can you describe the relevant data?
DR. LACY: This is a very exciting field, although I think the first thing we need to do is educate both patients and physicians that when we talk about antibiotics, we have to be very careful about how we frame the discussion, ie, we really need to focus on nonabsorbable antibiotics that remain in the GI tract. One of my concerns is that unless you know the area well, or unless you know the data well, you may randomly prescribe a number of different antibiotics for IBS, and this is not only potentially dangerous, but also unhelpful.
When I think about this topic, I think about the broad-spectrum antibiotic rifaximin, which is a nonabsorbable antibiotic that stays within the GI tract and focuses on typical gut bacteria, including gram-negative rods and anaerobic bacteria.
At present, there have been 5 randomized, double-blind, placebo-controlled studies looking at the effects of rifaximin in patients with nonconstipated IBS.46,47 In summary, these studies together include more than 2000 patients, and it’s been shown that rifaximin has improved not only global symptoms of IBS, but also individual symptoms of bloating, pain, discomfort, and diarrhea. Although it is not FDA-approved—and that is important to mention right now—there are ongoing studies that hopefully will lead to its approval.
If rifaximin isn’t available to your patient, another alternative would be neomycin. There is one small study48 showing that neomycin may be effective in IBS patients, but I am just mentioning it because it’s another nonabsorbable antibiotic that I think is safe and at least pathophysiologically makes sense.
DR. CASH: Dr. Harris, any thoughts regarding the use of complementary and alternative medicine for nonconstipation IBS?
DR. HARRIS: As we talk about that, I think we also need to mention some other basic concepts that I discuss with patients, and that is the benefit of exercise and sleep. There have been studies49,50 that have shown that when patients who have IBS don’t sleep well, they actually may have more pain the following day. So, I always try to emphasize on those important basic health concepts with my patients with IBS.
Additionally, there was one study last year that showed that exercise seems to improve abdominal pain as well in patients with IBS.51
As for complementary and alternative medicine, there are certain herbal medications, particularly peppermint oil, that can be used. There have been some small trials52 that have shown that peppermint oils works as a smooth muscle relaxant, although it’s best if it is in a form that gets digested further down the GI tract in the small bowel—so an encapsulated formulation is more useful—because otherwise, it can increase symptoms of gastroesophageal reflux disease.
Some patients find fennel tea and chamomile soothing, but there are no studies on their efficacy. There was one study that Bensoussan53 did a number of years ago that looked at Chinese herbal medicine, and I don’t know the components of the medicine, but the study did suggest that it had some benefit.
Lastly, these are not complementary therapies necessarily, but to address the mind-body connection of IBS patients, studies have shown that modalities such as mindfulness therapy and cognitive-behavioral therapy (CBT) can be helpful. There have also been some studies54–56 that have shown that using the CBT technique can help decrease the severity of abdominal pain and discomfort.
I believe there are also some studies with hypnotherapy, and Dr. Chang may be able to expand on those a little bit.
DR. CHANG: Those are more traditional behavioral therapies. There is a recent study57 showing that mindfulness meditation, which is becoming increasingly popular and used in other chronic illnesses, could be beneficial in reducing IBS symptoms.
There also have been acupuncture studies in IBS. If you look at uncontrolled studies, it seems that IBS is efficacious, but if you examine controlled studies with either sham acupuncture such as using needles that actually don’t penetrate deeply, the data are less robust and don’t really show much of a significant effect of IBS symptoms.58 The augmented interaction between the healthcare provider and patient is the beneficial component of these acupuncture therapy sessions.
DR. CASH: Dr. Chang, as a follow-up to that, what new and emerging therapeutics for IBS with constipation should we be looking toward in the next couple of years?
DR. CHANG: Well, there are 2 therapies that are currently being studied in either a phase II or phase III study. There’s an ongoing phase III study evaluating the efficacy of a kappa opioid receptor agonist, asimadoline, in relieving symptoms in patients with IBS with diarrhea. Asimadoline activates kappa opioid receptors, which are thought to become upregulated or increased in a sensitized chronic pain state such as in patients with particularly more severe symptoms.
A previous phase II study59 showed that asimadoline had particular efficacy in the IBS with diarrhea subgroup of patients who had more moderate pain. This is now being currently studied in a larger phase III trial.
There’s also an ongoing phase II trial with a tryptophan hydroxylase 1 inhibitor. This agent decreases the GI levels of serotonin. Basically, it works peripherally. There was a phase II trial where the higher dose of a tryptophan hydroxylase 1 inhibitor helped to decrease overall IBS symptoms and improve stool consistency in IBS with diarrhea.60
DR. LACY: There are 2 things I like to ask my patients as I finish the interview and examination: “What are you worried about? What are your fears and concerns?” And I try to address their concerns because data from our laboratory61 and from Dr. Chang’s laboratory62 showed that about 30% of patients are worried that their symptoms represent cancer, and I think it’s a good time to educate and reassure our patients about this.
The second thing I always ask is, “What are your goals.” I think we all see a lot of IBS patients each week, but it continues to strike me that everybody’s goals are very different, and some patients want to focus on just pain, some on just bloating, and some on altered bowel habits. So I’ve given up guessing what their goals are, and I just ask them point blank.
I think that’s very, very useful, and that lets a patient know that, once again, you’re focusing on them. It empowers them to choose the next step—whether they want to choose diet or medications and/or what type of medication.
DR. HARRIS: I would agree totally with Dr. Lacy’s excellent point. I do ask the patient, “What do you want to accomplish when you come to see me? What is your motivation for coming to see me? What problems or symptoms seem to be the most important to you?”
DR. CHANG: I agree with Dr. Lacy and Dr. Harris’s comments, and I would say that many patients, particularly in the clinic population, may have comorbid psychological symptoms, and some of the concerns and fears that were mentioned previously.
I think it’s important for healthcare providers to acknowledge that there may be an influence of the psychological symptoms on their disease or their symptoms, but they need not necessarily feel compelled to cure or fix them. I think that acknowledgment is helpful for patients and that reassurance and some education would be useful.
DR. CASH: I want to thank you all for taking the time to discuss this topic. It’s been very informative and a real pleasure.
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