Cover Story

Psychological Therapies in FGIDs: Stigma Persists While Data Accumulates

Psychological interventions are increasingly recognized as effective for treating patients with functional gastrointestinal disorders like irritable bowel syndrome, functional constipation, functional dyspepsia and others. However, a variety of factors present challenges to delivering these treatments to patients.

In particular, persistent stigmatization of functional GI disorders and their nonmedical treatments can inhibit the integration of psychological interventions into traditional medical care scenarios, and can especially make early intervention difficult. Notably, it is often health care providers rather than patients who tend to be most skeptical of psychological treatments for FGIDs, despite a wealth of supporting data, according to experts interviewed by Healio Gastroenterology.

To better understand the basis for psychological treatments like cognitive behavioral therapy and hypnotherapy in FGIDs, as well as recent advances in these treatment approaches and the barriers to their implementation, we reached out to a number of leaders in the field of GI psychology.

“We’ve now gotten long past the simplistic understanding that many medical problems, their etiology, and their maintenance is understood soley by focusing on what’s going on within the physiology of an individual,” Rona L. Levy, PhD, of the Behavioral Medicine Research Group, School of Social Work, University of Washington, Seattle, and chair of the Biopsychosocial Chapter Committee of Rome IV, told Healio Gastroenterology. “We’ve come to realize there is a continuous interaction among what is going on cognitively, physiologically and environmentally for an individual — what they’re thinking, what they’re feeling, how they are affected by what is going on around them all interact to produce what we call symptoms. Understanding the role of central nervous system processing — simply put, the brain — is key in all of this.”

Rona Levy

Biopsychosocial Model

To treat FGIDs effectively, health care providers must understand that complex interactions between environmental, psychological and biological factors contribute to their onset and maintenance, according to a recent multidisciplinary consensus report published as the Rome IV special issue in Gastroenterology. In it, Douglas A. Drossman, MD, president of the Rome Foundation and co-director emeritus of the Center for Functional GI and Motility Disorders at University of North Carolina, Chapel Hill, and colleagues described addressing all of these factors within a biopsychosocial framework as a conditio sine qua non for adequate treatment of FGIDs.

First developed by the American internist and psychiatrist George Engel in 1977 at the University of Rochester Medical Center, the biopsychosocial model was extrapolated to FGIDs by Drossman about 20 years later.

“Since that time, the biopsychosocial model has been adopted and incorporated by the Rome Foundation, because it helps explain FGIDs, which don’t have a structural basis for the symptoms,” Drossman told Healio Gastroenterology. In clinical practice, this framework helps the clinician to “integrate biologic, psychologic and social processes affecting the individual, which means getting a more complete history that leads to a better understanding of the illness and better treatment.”

Douglas Drossman

In their report, Drossman and colleagues recommended a brief psychosocial assessment during the clinical exam to screen for patients who may be at risk for refractory symptoms, poor response to treatment or low quality of life, and to determine if a more thorough evaluation with a health psychologist or psychiatrist is necessary. During this assessment, clinicians should screen for psychological factors that have been associated with FGIDs, which include “increased psychological distress, somatization, stressful life events, history of sexual and physical abuse, and maladaptive coping,” according to a review article by Reed-Knight and colleagues. In particular, depression affects about 30% of FGID patients and anxiety affects between 30% to 50%, by some estimates.

In pediatric patients, part of the environmental factors that need to be considered are ongoing parental influences; Levy and colleagues, for example, have shown that children whose parents have IBS and reinforce “illness behavior” have more severe stomach aches and more school absences than their peers.

In a prospective study, “we found children who had unexplained stomach pain tended to have parents who responded more in a way we called ‘solicitously’ to GI symptoms,” Levy said. “For example, if you have a child who shows a little bit of discomfort and a parent is hypervigilant to that, the parent may react in a certain way that basically cues the child that this is something worth reacting to. That may, in turn, train the child to notice the next time they have a sensation like this, and perhaps even be concerned about it.” In effect, this can set up a “loop” where GI sensations, anxiety, hypervigilance, and illness behaviors all continuously reinforce each other, she said.

“We then developed some interventions where we trained children and parents to react differently, and then eventually we just worked with parents alone and showed that if you can change the way parents respond to their children, ... then that actually decreases the child’s illness behavior, and the levels of GI symptoms that the child reports,” Levy said.

Applying the biopsychosocial model in the clinical evaluation of FGIDs is especially useful in developing a narrative to explain the disorder to a patient, according to Laurie Keefer, PhD, a GI health psychologist and Director of Psychobehavioral Research at the Ichan School of Medicine at Mount Sinai in New York City, and co-chair of the Rome IV Centrally Mediated Disorders of GI Pain Chapter Committee.

“The biopsychosocial model allows us to really look at a whole patient,” Keefer told Healio Gastroenterology. “In the absence of any organic findings, it’s very difficult for physicians to explain to patients why they have these symptoms, so if you can incorporate a story that makes sense to the patient — for example, you got an infection, it messed up your GI tract, but then you also happened to be under stress at the time it happened, and that’s why it’s maintained [or] maybe you had an early life adversity, there’s a lot of data on child abuse and other early life trauma that affects the development of the GI tract, and makes people more sensitive to pain and more likely to develop these conditions — it can be a much more helpful, informative approach than if you were just to say, ‘We couldn’t find anything on exam, there’s no excess bacteria, there’s no inflammation, so it must be all in your head,’ which is historically how we’ve dealt with these types of conditions that don’t have obvious biomarkers.”

Another important feature of the biopsychosocial model is that it provides a bidirectional framework to explain the relationship between GI symptoms and anxiety and depression, Keefer said. While anxiety and depression can exacerbate FGIDs, “these conditions also drive depression. If you feel like you can’t leave the house because you have chronic diarrhea, and you stop seeing your friends, you feel depressed. So it’s a multidirectional or circular model you can use rather than just saying depression and anxiety cause FGIDs.”

However, recent work by Nicholas Talley, MD, Chair of the Rome IV Gastroduodenal Chapter committee, and colleagues from the University of Newcastle, Australia, has suggested there may be subgroups of patients with FGIDs for whom either gut symptoms or psychological symptoms alone are the primary drivers of their FGID, which Talley said could be a paradigm shifting realization.

Nicholas Talley

Gut-to-Brain vs. Brain-to-Gut

“We think there are two distinct subsets of functional gut syndromes, and that has implications for therapy,” Talley said in an interview at ACG 2016 in Las Vegas. “You treat the anxiety or depression if it’s the primary driver of symptoms, but if it’s a secondary phenomenon, you’ve actually got to target the gut to get this success.”

After surveying a prospective random population sample of 1,900 individuals from Australia (mean age, 57 years; 53% women) in 2012 and a year later, Talley and colleagues reported that 6.4% of respondents developed new onset IBS, 7.2% developed functional dyspepsia, and almost 50% who had IBS or functional dyspepsia at baseline no longer had symptoms.

Participants had a significantly higher risk for developing an FGID if they had higher anxiety or depression levels at baseline, which suggest brain-to-gut interactions in these participants, but not in participants who already had an FGID, the investigators wrote.

Furthermore, among participants without higher anxiety and depression levels at baseline, those who already had an FGID had significantly higher anxiety and depression levels at follow-up. These patterns were not observed in “those who already had elevated anxiety or depression, implicating primary gut-to-brain pathways operate in a major subset with these disorders,” they wrote.

Finally, 215 respondents had a mood disorder at baseline, and 30 of them had an FGID at 1 year, while 309 respondents had an FGID at baseline, and 60 of them had a mood disorder at 1 year, so a mood disorder preceded an FGID in one-third of these participants.

“We speculate that there’s a group of people who will develop gut symptoms because in some cases they get gut inflammation, and that inflammatory process and/or changes in the microbiome could well drive the brain changes that we’re seeing,” Talley said. He added that he and his group have now done three independent studies in three different populations with similar results, and they are performing ongoing research on a cytokine pathway that may be involved, and on the role of bacterial dysbiosis in humans.

These findings, he said, could eventually help predict which FGID patients are most likely to respond to psychological therapies, and who will be most likely to have a sustained response. “We speculate the people who have anxiety as the primary driver will be the best responders to psychological intervention,” which currently have about a 60% to 70% response rate at most, he noted.

Informed by the biopsychosocial model, researchers have explored the usefulness of these psychological interventions for addressing the environmental and psychological factors that may impact GI symptoms, and have demonstrated success with a variety of approaches. A recent meta-analysis by Laird and colleagues, for example, showed significant short- and long-term reductions in GI symptoms among patients with IBS who underwent interventions like cognitive or cognitive-behavioral therapy, relaxation or hypnosis.

According to Levy, to date, cognitive-behavioral therapy shows the most promise.

Cognitive-Behavioral Therapy

Cognitive behavioral therapies are a family of therapeutic techniques that aim to teach patients skills for recognizing and modifying their thoughts, emotions and behavioral responses, and in the context of FGIDs, these skills can help manage their symptoms. CBT is “problem-focused, goal-directed, and time-limited [and] includes a combination of techniques including self-monitoring, cognitive restructuring, problem solving, exposure, and relaxation methods,” Drossman and colleagues wrote.

“Cognitive-behavioral therapy is one of the more important treatment modalities,” he said. “We did an NIH study 12 years ago looking at several hundred people with IBS, and showed that there was a 70% clinical response rate with CBT compared to 38% of people who received education instead. This was highly significant, and others have since replicated that work.”

Indeed, Reed-Knight and colleagues recently confirmed that several studies have shown CBT “is effective in treating both the symptoms and disability associated with abdominal pain, IBS, dyspepsia and fecal incontinence.”

The fact that CBT is effective in all of these different FGIDs is especially valuable, according to Keefer.

“All these FGIDs tend to have similar cognitive-affective processes, so most [CBTs] can be tailored to specific symptoms, and it doesn’t really matter if the person has heartburn or irritable bowel syndrome or something else,” she said. “Most of the CBT approaches are what we call trans-diagnostics, so it doesn’t really matter what the condition is once we know what the treatment targets are.”

Teaching patients new skills to better respond to their GI symptoms, through relaxing and by continuing with their daily activities, and also teaching a patients’ family and friends to encourage “wellness behaviors” rather than “illness behaviors” are useful components of CBT, according to Levy. One of the most important aspects is in helping patients change the way they evaluate their GI symptoms, interpreting them as physiological “sensations” and not harmful symptoms.

“A minor stomach discomfort or gurgle, for example, doesn’t mean there’s a major issue going on; it’s a physiological sensation which may or may not be a symptom of something,” she said. “How one interprets these sensations is a major issue that should be addressed in any form of therapy. Of course, the cautionary note in this is that patients and parents of patients should be knowledgeable about, and not ignore ‘red flag’ symptoms of serious disease, which are best clarified by health care personnel.”

This relates to the concept of “interoceptive fear conditioning,” which was recently studied by a group from Belgium, who randomly assigned 52 healthy individuals to undergo esophageal balloon distention at painful and nonpainful intensities in different sequences. They determined that fear of innocuous GI sensations can be learned by healthy adults, suggesting this may play a role in the development of FGIDs.

This study “demonstrated for the first time that you could condition fear of normal sensations, and ... it shows that CBT — which is based on the assumption that people develop skills deficits around a specific problem — can be geared toward GI fear in particular, like fear of pain or fear of food,” Keefer said.

In an editorial commenting on the study, Keefer noted that interoceptive exposure, a specific kind of CBT that targets extinction of benign GI sensations, could be useful in treating FGIDs.

“The data is not quite ready for prime time yet, but the concept of adding an element to traditional CBT called exposure, involves having a patient confront the things that they’re afraid of,” she said. “For example, in diarrhea-predominant IBS you might have a patient purposely go out and eat something that’s going to cause them diarrhea and manage it, because they’re fearing that worst-case scenario. You might have somebody tighten their belt really tight and create abdominal pain or bloating, and then learn to regulate that sensation. So it’s a little more experiential, and it’s much more targeted toward specific fear of symptoms.”

While CBT is the most well established psychological intervention for FGIDs, and continues to become more targeted through work by Keefer and others, hypnosis, according to Drossman, is the second most important.

Gut-Directed Hypnotherapy

Hypnotherapy in FGIDs involves the use of gut-directed hypnotic suggestions to induce feelings of relaxation and wellbeing, and IBS-specific protocols have been developed by researchers like Peter Whorwell, MD, PhD, of the University Hospital of South Manchester, U.K., and Olafur Palsson, PsyD, at UNC, Drossman said.

Despite the obvious stigma surrounding its use in medical care, there is evidence to support the use of hypnotherapy in FGIDs, especially in refractory IBS, Keefer said.

For example, a recent randomized controlled trial by Peters and colleagues showed gut-directed hypnotherapy was just as effective as the low FODMAP diet for long-term relief of IBS symptoms, and even better in terms of psychological indices.

“Over seven sessions or so you see 80% improvement in really refractory cases, which is amazing,” Keefer said.

“Most patients like it, because unlike meditation where the patient has to sit down and generate their own level of focus, which is not great if they are highly symptomatic or are a worrier, hypnosis is delivered much like an infusion or an IV, so we say to patients it’s like the hypnotic trance is sort of the syringe and then the dose is the very specific suggestions we make about your recovery,” Keefer said.

Another advantage of gut-directed hypnotherapy, according to Drossman, is that most people are hypnotizeable. “There are certain ways you can assess a patient’s hypnotizeability, but it really comes down to feeling comfortable and agreeing to go through the process, that is, to make yourself open to the idea of suggestion,” he said. “But, we all are hypnotized all the time, [like] when you drive and daydream, that’s a form of hypnosis. It takes active mental energy to prevent it, so if someone’s anxious about it or doesn’t want it they won’t get hypnotized, but if you let yourself do it, it can be done fairly naturally, through a hypnotist or through a DVD or CD.”

Others, including Levy, are a bit more cautious when recommending hypnotherapy for FGIDs, particularly due to a preference for more data and the promise that’s already been shown for CBT.

“There are components of hypnotherapy which may be effective, ... but I don’t think hypnotherapy in and of itself is a magic bullet,” she said. “I don’t think it’s particularly more effective than some aspects of CBT, and I think the jury’s still out on some of the methodological aspects of some of those studies.”

However, if one does refer an FGID patient for hypnotherapy, Keefer emphasized the importance of approaching it as a pain management strategy in these patients, rather than a traditional psychotherapeutic one. “It is a medical intervention that’s been used in surgery. ... Before we had anesthesia, people were hypnotized,” she noted, “and the last thing these patients want to hear is that the doctor thinks it’s in their head.”

This sort of stigmatization, which experts said affects all functional somatic disorders, is one of the major challenges to delivering psychological therapies to patients with FGIDs.

Barriers to Implementation

The main reason patients with FGIDs are so stigmatized compared with those with organic disease goes back to the dualistic Des Cartesian separation of the mind and body, Drossman said, referencing his TED talk on the subject.

“Our heritage in medicine has been to look for structural abnormalities, like pathologies and X-rays and endoscopy, ... and if you don’t find something, you consider it psychiatric,” he said. “As a result of that, doctors who see a patient with an FGID may feel they can’t handle it, and they disclaim it and say it’s a psychiatric problem or stress, and that the patient has to learn to relax.”

Approaching these patients using biopsychosocial model is the solution, he said, “to say that that the pain and the psychologic distress could be a result of the GI symptoms, and is another component that needs to be treated by effective and integrated strategies like CBT, hypnosis, meditation and the like. If you do that, the patient can be more accepting, but what we have now is a system where patients and doctors in general separate out stress as being a factor, [and] they disown their responsibility for treating the medical problem because they see it now as psychiatric as opposed to an integrated model.”

Beyond this fundamental challenge of approaching FGIDs through the proper clinical framework, Reed-Knight and colleagues note that “lack of GI-trained therapists, low referral rates in the absence of clear psychological distress, and poor insurance coverage for these treatments,” are why “psychological therapies are not available to most patients ... despite overwhelmingly positive findings.” In their review article, they suggest various integrated care models, involving the collaboration of gastroenterologists and psychologists, can deliver comprehensive care, reduce stigma associated with psychological care, increase patient satisfaction and lower costs. Of course, they acknowledge site-specific needs and the need for these models to be adaptive may make implementation more difficult.

One of the biggest challenges to delivering psychological treatments to FGID patients is simply the lack of trained GI psychologists, according to Keefer.

“One of the criticisms I get when I talk about the benefits of these treatments ... is, ‘Who is going to provide them?’ So the doctors tend to get really frustrated,” she said. “To meet that challenge, we’re starting to see an increase in things like minimal contact therapy and online delivery of hypnosis,” so trained therapists can deliver these treatments more widely.

Yet another challenge, she said, is “getting physicians comfortable with the referral early on in the list of treatments that they offer the patient. The last thing you want to do is send the patient for psychotherapy after everything else has failed, because then it seems like this is only for people who fail treatment. Even if you don’t refer them right away, at least start the conversation around the benefits of those treatments.”

Fortunately, Keefer said, the patients seem to be more open to these treatments nowadays, and feel less stigmatized about seeking psychological therapy.

“Most patients are open to anything that will help them feel better,” she said. “I think that has changed over the years that I’ve been doing this, where patients used to feel like it was stigmatizing to see a psychologist. Use of the term health psychologist has really made a big difference for people. We’re not referring you to a traditional psychologist, but a health psychologist that specializes in behavioral interventions for medical problems. So patients seem to be a lot more open than they used to be.”

To physicians who remain skeptical of the value of psychological treatments compared with more traditional therapies for these disorders, Levy’s parting words for them are simple: “Look at the data.” – by Adam Leitenberger

Disclosures: Drossman and Levy report no relevant financial disclosures. Keefer reports she has served on the scientific advisory board for MetaME Health. Talley reports he has served on the advisory committee or boards of the Australian Medical Council, MBS Review Taskforce, NHMRC CI, Sax Institute and The Committee of Presidents of the Medical Colleges; has served as a consultant for Adelphi Values, Allergan, GI Therapies and Yuhan; has received grant/research support from Abbott Pharmaceuticals, Janssen, NHMRC CI, P­fizer, Prometheus, Rome Foundation and Salix; and holds patents related to biomarkers of irritable bowel syndrome, EoE pathway, licensing questionnaires and nanotechnology.

Psychological interventions are increasingly recognized as effective for treating patients with functional gastrointestinal disorders like irritable bowel syndrome, functional constipation, functional dyspepsia and others. However, a variety of factors present challenges to delivering these treatments to patients.

In particular, persistent stigmatization of functional GI disorders and their nonmedical treatments can inhibit the integration of psychological interventions into traditional medical care scenarios, and can especially make early intervention difficult. Notably, it is often health care providers rather than patients who tend to be most skeptical of psychological treatments for FGIDs, despite a wealth of supporting data, according to experts interviewed by Healio Gastroenterology.

To better understand the basis for psychological treatments like cognitive behavioral therapy and hypnotherapy in FGIDs, as well as recent advances in these treatment approaches and the barriers to their implementation, we reached out to a number of leaders in the field of GI psychology.

“We’ve now gotten long past the simplistic understanding that many medical problems, their etiology, and their maintenance is understood soley by focusing on what’s going on within the physiology of an individual,” Rona L. Levy, PhD, of the Behavioral Medicine Research Group, School of Social Work, University of Washington, Seattle, and chair of the Biopsychosocial Chapter Committee of Rome IV, told Healio Gastroenterology. “We’ve come to realize there is a continuous interaction among what is going on cognitively, physiologically and environmentally for an individual — what they’re thinking, what they’re feeling, how they are affected by what is going on around them all interact to produce what we call symptoms. Understanding the role of central nervous system processing — simply put, the brain — is key in all of this.”

Rona Levy

Biopsychosocial Model

To treat FGIDs effectively, health care providers must understand that complex interactions between environmental, psychological and biological factors contribute to their onset and maintenance, according to a recent multidisciplinary consensus report published as the Rome IV special issue in Gastroenterology. In it, Douglas A. Drossman, MD, president of the Rome Foundation and co-director emeritus of the Center for Functional GI and Motility Disorders at University of North Carolina, Chapel Hill, and colleagues described addressing all of these factors within a biopsychosocial framework as a conditio sine qua non for adequate treatment of FGIDs.

First developed by the American internist and psychiatrist George Engel in 1977 at the University of Rochester Medical Center, the biopsychosocial model was extrapolated to FGIDs by Drossman about 20 years later.

“Since that time, the biopsychosocial model has been adopted and incorporated by the Rome Foundation, because it helps explain FGIDs, which don’t have a structural basis for the symptoms,” Drossman told Healio Gastroenterology. In clinical practice, this framework helps the clinician to “integrate biologic, psychologic and social processes affecting the individual, which means getting a more complete history that leads to a better understanding of the illness and better treatment.”

Douglas Drossman

In their report, Drossman and colleagues recommended a brief psychosocial assessment during the clinical exam to screen for patients who may be at risk for refractory symptoms, poor response to treatment or low quality of life, and to determine if a more thorough evaluation with a health psychologist or psychiatrist is necessary. During this assessment, clinicians should screen for psychological factors that have been associated with FGIDs, which include “increased psychological distress, somatization, stressful life events, history of sexual and physical abuse, and maladaptive coping,” according to a review article by Reed-Knight and colleagues. In particular, depression affects about 30% of FGID patients and anxiety affects between 30% to 50%, by some estimates.

In pediatric patients, part of the environmental factors that need to be considered are ongoing parental influences; Levy and colleagues, for example, have shown that children whose parents have IBS and reinforce “illness behavior” have more severe stomach aches and more school absences than their peers.

PAGE BREAK

In a prospective study, “we found children who had unexplained stomach pain tended to have parents who responded more in a way we called ‘solicitously’ to GI symptoms,” Levy said. “For example, if you have a child who shows a little bit of discomfort and a parent is hypervigilant to that, the parent may react in a certain way that basically cues the child that this is something worth reacting to. That may, in turn, train the child to notice the next time they have a sensation like this, and perhaps even be concerned about it.” In effect, this can set up a “loop” where GI sensations, anxiety, hypervigilance, and illness behaviors all continuously reinforce each other, she said.

“We then developed some interventions where we trained children and parents to react differently, and then eventually we just worked with parents alone and showed that if you can change the way parents respond to their children, ... then that actually decreases the child’s illness behavior, and the levels of GI symptoms that the child reports,” Levy said.

Applying the biopsychosocial model in the clinical evaluation of FGIDs is especially useful in developing a narrative to explain the disorder to a patient, according to Laurie Keefer, PhD, a GI health psychologist and Director of Psychobehavioral Research at the Ichan School of Medicine at Mount Sinai in New York City, and co-chair of the Rome IV Centrally Mediated Disorders of GI Pain Chapter Committee.

“The biopsychosocial model allows us to really look at a whole patient,” Keefer told Healio Gastroenterology. “In the absence of any organic findings, it’s very difficult for physicians to explain to patients why they have these symptoms, so if you can incorporate a story that makes sense to the patient — for example, you got an infection, it messed up your GI tract, but then you also happened to be under stress at the time it happened, and that’s why it’s maintained [or] maybe you had an early life adversity, there’s a lot of data on child abuse and other early life trauma that affects the development of the GI tract, and makes people more sensitive to pain and more likely to develop these conditions — it can be a much more helpful, informative approach than if you were just to say, ‘We couldn’t find anything on exam, there’s no excess bacteria, there’s no inflammation, so it must be all in your head,’ which is historically how we’ve dealt with these types of conditions that don’t have obvious biomarkers.”

Another important feature of the biopsychosocial model is that it provides a bidirectional framework to explain the relationship between GI symptoms and anxiety and depression, Keefer said. While anxiety and depression can exacerbate FGIDs, “these conditions also drive depression. If you feel like you can’t leave the house because you have chronic diarrhea, and you stop seeing your friends, you feel depressed. So it’s a multidirectional or circular model you can use rather than just saying depression and anxiety cause FGIDs.”

However, recent work by Nicholas Talley, MD, Chair of the Rome IV Gastroduodenal Chapter committee, and colleagues from the University of Newcastle, Australia, has suggested there may be subgroups of patients with FGIDs for whom either gut symptoms or psychological symptoms alone are the primary drivers of their FGID, which Talley said could be a paradigm shifting realization.

Nicholas Talley

Gut-to-Brain vs. Brain-to-Gut

“We think there are two distinct subsets of functional gut syndromes, and that has implications for therapy,” Talley said in an interview at ACG 2016 in Las Vegas. “You treat the anxiety or depression if it’s the primary driver of symptoms, but if it’s a secondary phenomenon, you’ve actually got to target the gut to get this success.”

PAGE BREAK

After surveying a prospective random population sample of 1,900 individuals from Australia (mean age, 57 years; 53% women) in 2012 and a year later, Talley and colleagues reported that 6.4% of respondents developed new onset IBS, 7.2% developed functional dyspepsia, and almost 50% who had IBS or functional dyspepsia at baseline no longer had symptoms.

Participants had a significantly higher risk for developing an FGID if they had higher anxiety or depression levels at baseline, which suggest brain-to-gut interactions in these participants, but not in participants who already had an FGID, the investigators wrote.

Furthermore, among participants without higher anxiety and depression levels at baseline, those who already had an FGID had significantly higher anxiety and depression levels at follow-up. These patterns were not observed in “those who already had elevated anxiety or depression, implicating primary gut-to-brain pathways operate in a major subset with these disorders,” they wrote.

Finally, 215 respondents had a mood disorder at baseline, and 30 of them had an FGID at 1 year, while 309 respondents had an FGID at baseline, and 60 of them had a mood disorder at 1 year, so a mood disorder preceded an FGID in one-third of these participants.

“We speculate that there’s a group of people who will develop gut symptoms because in some cases they get gut inflammation, and that inflammatory process and/or changes in the microbiome could well drive the brain changes that we’re seeing,” Talley said. He added that he and his group have now done three independent studies in three different populations with similar results, and they are performing ongoing research on a cytokine pathway that may be involved, and on the role of bacterial dysbiosis in humans.

These findings, he said, could eventually help predict which FGID patients are most likely to respond to psychological therapies, and who will be most likely to have a sustained response. “We speculate the people who have anxiety as the primary driver will be the best responders to psychological intervention,” which currently have about a 60% to 70% response rate at most, he noted.

Informed by the biopsychosocial model, researchers have explored the usefulness of these psychological interventions for addressing the environmental and psychological factors that may impact GI symptoms, and have demonstrated success with a variety of approaches. A recent meta-analysis by Laird and colleagues, for example, showed significant short- and long-term reductions in GI symptoms among patients with IBS who underwent interventions like cognitive or cognitive-behavioral therapy, relaxation or hypnosis.

According to Levy, to date, cognitive-behavioral therapy shows the most promise.

Cognitive-Behavioral Therapy

Cognitive behavioral therapies are a family of therapeutic techniques that aim to teach patients skills for recognizing and modifying their thoughts, emotions and behavioral responses, and in the context of FGIDs, these skills can help manage their symptoms. CBT is “problem-focused, goal-directed, and time-limited [and] includes a combination of techniques including self-monitoring, cognitive restructuring, problem solving, exposure, and relaxation methods,” Drossman and colleagues wrote.

“Cognitive-behavioral therapy is one of the more important treatment modalities,” he said. “We did an NIH study 12 years ago looking at several hundred people with IBS, and showed that there was a 70% clinical response rate with CBT compared to 38% of people who received education instead. This was highly significant, and others have since replicated that work.”

Indeed, Reed-Knight and colleagues recently confirmed that several studies have shown CBT “is effective in treating both the symptoms and disability associated with abdominal pain, IBS, dyspepsia and fecal incontinence.”

The fact that CBT is effective in all of these different FGIDs is especially valuable, according to Keefer.

“All these FGIDs tend to have similar cognitive-affective processes, so most [CBTs] can be tailored to specific symptoms, and it doesn’t really matter if the person has heartburn or irritable bowel syndrome or something else,” she said. “Most of the CBT approaches are what we call trans-diagnostics, so it doesn’t really matter what the condition is once we know what the treatment targets are.”

PAGE BREAK

Teaching patients new skills to better respond to their GI symptoms, through relaxing and by continuing with their daily activities, and also teaching a patients’ family and friends to encourage “wellness behaviors” rather than “illness behaviors” are useful components of CBT, according to Levy. One of the most important aspects is in helping patients change the way they evaluate their GI symptoms, interpreting them as physiological “sensations” and not harmful symptoms.

“A minor stomach discomfort or gurgle, for example, doesn’t mean there’s a major issue going on; it’s a physiological sensation which may or may not be a symptom of something,” she said. “How one interprets these sensations is a major issue that should be addressed in any form of therapy. Of course, the cautionary note in this is that patients and parents of patients should be knowledgeable about, and not ignore ‘red flag’ symptoms of serious disease, which are best clarified by health care personnel.”

This relates to the concept of “interoceptive fear conditioning,” which was recently studied by a group from Belgium, who randomly assigned 52 healthy individuals to undergo esophageal balloon distention at painful and nonpainful intensities in different sequences. They determined that fear of innocuous GI sensations can be learned by healthy adults, suggesting this may play a role in the development of FGIDs.

This study “demonstrated for the first time that you could condition fear of normal sensations, and ... it shows that CBT — which is based on the assumption that people develop skills deficits around a specific problem — can be geared toward GI fear in particular, like fear of pain or fear of food,” Keefer said.

In an editorial commenting on the study, Keefer noted that interoceptive exposure, a specific kind of CBT that targets extinction of benign GI sensations, could be useful in treating FGIDs.

“The data is not quite ready for prime time yet, but the concept of adding an element to traditional CBT called exposure, involves having a patient confront the things that they’re afraid of,” she said. “For example, in diarrhea-predominant IBS you might have a patient purposely go out and eat something that’s going to cause them diarrhea and manage it, because they’re fearing that worst-case scenario. You might have somebody tighten their belt really tight and create abdominal pain or bloating, and then learn to regulate that sensation. So it’s a little more experiential, and it’s much more targeted toward specific fear of symptoms.”

While CBT is the most well established psychological intervention for FGIDs, and continues to become more targeted through work by Keefer and others, hypnosis, according to Drossman, is the second most important.

Gut-Directed Hypnotherapy

Hypnotherapy in FGIDs involves the use of gut-directed hypnotic suggestions to induce feelings of relaxation and wellbeing, and IBS-specific protocols have been developed by researchers like Peter Whorwell, MD, PhD, of the University Hospital of South Manchester, U.K., and Olafur Palsson, PsyD, at UNC, Drossman said.

Despite the obvious stigma surrounding its use in medical care, there is evidence to support the use of hypnotherapy in FGIDs, especially in refractory IBS, Keefer said.

For example, a recent randomized controlled trial by Peters and colleagues showed gut-directed hypnotherapy was just as effective as the low FODMAP diet for long-term relief of IBS symptoms, and even better in terms of psychological indices.

“Over seven sessions or so you see 80% improvement in really refractory cases, which is amazing,” Keefer said.

“Most patients like it, because unlike meditation where the patient has to sit down and generate their own level of focus, which is not great if they are highly symptomatic or are a worrier, hypnosis is delivered much like an infusion or an IV, so we say to patients it’s like the hypnotic trance is sort of the syringe and then the dose is the very specific suggestions we make about your recovery,” Keefer said.

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Another advantage of gut-directed hypnotherapy, according to Drossman, is that most people are hypnotizeable. “There are certain ways you can assess a patient’s hypnotizeability, but it really comes down to feeling comfortable and agreeing to go through the process, that is, to make yourself open to the idea of suggestion,” he said. “But, we all are hypnotized all the time, [like] when you drive and daydream, that’s a form of hypnosis. It takes active mental energy to prevent it, so if someone’s anxious about it or doesn’t want it they won’t get hypnotized, but if you let yourself do it, it can be done fairly naturally, through a hypnotist or through a DVD or CD.”

Others, including Levy, are a bit more cautious when recommending hypnotherapy for FGIDs, particularly due to a preference for more data and the promise that’s already been shown for CBT.

“There are components of hypnotherapy which may be effective, ... but I don’t think hypnotherapy in and of itself is a magic bullet,” she said. “I don’t think it’s particularly more effective than some aspects of CBT, and I think the jury’s still out on some of the methodological aspects of some of those studies.”

However, if one does refer an FGID patient for hypnotherapy, Keefer emphasized the importance of approaching it as a pain management strategy in these patients, rather than a traditional psychotherapeutic one. “It is a medical intervention that’s been used in surgery. ... Before we had anesthesia, people were hypnotized,” she noted, “and the last thing these patients want to hear is that the doctor thinks it’s in their head.”

This sort of stigmatization, which experts said affects all functional somatic disorders, is one of the major challenges to delivering psychological therapies to patients with FGIDs.

Barriers to Implementation

The main reason patients with FGIDs are so stigmatized compared with those with organic disease goes back to the dualistic Des Cartesian separation of the mind and body, Drossman said, referencing his TED talk on the subject.

“Our heritage in medicine has been to look for structural abnormalities, like pathologies and X-rays and endoscopy, ... and if you don’t find something, you consider it psychiatric,” he said. “As a result of that, doctors who see a patient with an FGID may feel they can’t handle it, and they disclaim it and say it’s a psychiatric problem or stress, and that the patient has to learn to relax.”

Approaching these patients using biopsychosocial model is the solution, he said, “to say that that the pain and the psychologic distress could be a result of the GI symptoms, and is another component that needs to be treated by effective and integrated strategies like CBT, hypnosis, meditation and the like. If you do that, the patient can be more accepting, but what we have now is a system where patients and doctors in general separate out stress as being a factor, [and] they disown their responsibility for treating the medical problem because they see it now as psychiatric as opposed to an integrated model.”

Beyond this fundamental challenge of approaching FGIDs through the proper clinical framework, Reed-Knight and colleagues note that “lack of GI-trained therapists, low referral rates in the absence of clear psychological distress, and poor insurance coverage for these treatments,” are why “psychological therapies are not available to most patients ... despite overwhelmingly positive findings.” In their review article, they suggest various integrated care models, involving the collaboration of gastroenterologists and psychologists, can deliver comprehensive care, reduce stigma associated with psychological care, increase patient satisfaction and lower costs. Of course, they acknowledge site-specific needs and the need for these models to be adaptive may make implementation more difficult.

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One of the biggest challenges to delivering psychological treatments to FGID patients is simply the lack of trained GI psychologists, according to Keefer.

“One of the criticisms I get when I talk about the benefits of these treatments ... is, ‘Who is going to provide them?’ So the doctors tend to get really frustrated,” she said. “To meet that challenge, we’re starting to see an increase in things like minimal contact therapy and online delivery of hypnosis,” so trained therapists can deliver these treatments more widely.

Yet another challenge, she said, is “getting physicians comfortable with the referral early on in the list of treatments that they offer the patient. The last thing you want to do is send the patient for psychotherapy after everything else has failed, because then it seems like this is only for people who fail treatment. Even if you don’t refer them right away, at least start the conversation around the benefits of those treatments.”

Fortunately, Keefer said, the patients seem to be more open to these treatments nowadays, and feel less stigmatized about seeking psychological therapy.

“Most patients are open to anything that will help them feel better,” she said. “I think that has changed over the years that I’ve been doing this, where patients used to feel like it was stigmatizing to see a psychologist. Use of the term health psychologist has really made a big difference for people. We’re not referring you to a traditional psychologist, but a health psychologist that specializes in behavioral interventions for medical problems. So patients seem to be a lot more open than they used to be.”

To physicians who remain skeptical of the value of psychological treatments compared with more traditional therapies for these disorders, Levy’s parting words for them are simple: “Look at the data.” – by Adam Leitenberger

Disclosures: Drossman and Levy report no relevant financial disclosures. Keefer reports she has served on the scientific advisory board for MetaME Health. Talley reports he has served on the advisory committee or boards of the Australian Medical Council, MBS Review Taskforce, NHMRC CI, Sax Institute and The Committee of Presidents of the Medical Colleges; has served as a consultant for Adelphi Values, Allergan, GI Therapies and Yuhan; has received grant/research support from Abbott Pharmaceuticals, Janssen, NHMRC CI, P­fizer, Prometheus, Rome Foundation and Salix; and holds patents related to biomarkers of irritable bowel syndrome, EoE pathway, licensing questionnaires and nanotechnology.