Central Neuromodulators in Irritable Bowel Syndrome: Why, How, and When.

Irritable bowel syndrome (IBS) is responsive to treatments using central neuromodulators. Central neuromodulators work by enhancing the synaptic transmission of 5-hydroxytryptamine, noradrenalin, and dopamine, achieving a slower regulation or desensitization of their postsynaptic receptors. Central neuromodulators act on receptors along the brain-gut axis, so they are useful in treating psychiatric comorbidities, modifying gut motility, improving central downregulation of visceral signals, and enhancing neurogenesis in patients with IBS. Choosing a central neuromodulator for treating IBS should be according to the pharmacological properties and predominant symptoms. The first-line treatment for pain management in IBS is using tricyclic antidepressants. An alternative for pain management is the serotonin and noradrenaline reuptake inhibitors. Selective serotonin reuptake inhibitors are useful when symptoms of anxiety and hypervigilance are dominant but are not helpful for treating abdominal pain. The predominant bowel habit is helpful when choosing a neuromodulator to treat IBS; selective serotonin reuptake inhibitors help constipation, not pain, but may cause diarrhea; tricyclic antidepressants help diarrhea but may cause constipation. A clinical response may occur in 6-8 weeks, but long-term treatment (usually 6-12 months) is required after the initial response to prevent relapse. Augmentation therapy may be beneficial when the therapeutic effect of the first agent is incomplete or associated with side effects. It is recommended to reduce the dose of the first agent and add a second complementary treatment. This may include an atypical antipsychotic or brain-gut behavioral treatment. When tapering central neuromodulators, the dose should be reduced slowly over 4 weeks but may take longer when discontinuation effects occur.

Worldwide population prevalence and impact of sub-diagnostic gastrointestinal symptoms.

BACKGROUND: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms. AIMS: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs. METHODS: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions. RESULTS: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment. CONCLUSIONS: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice.

Face-to-face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population-based research.

BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.

Factor Analysis of the Rome IV Criteria for Major Disorders of Gut-Brain Interaction (DGBI) Globally and Across Geographical, Sex, and Age Groups.

BACKGROUND & AIMS: The Rome criteria are widely accepted for diagnosing disorders of gut-brain interaction, but their global applicability has been debated. This study aimed to evaluate the validity of the Rome IV criteria by factor analysis globally, across geographical regions, by sex, and by age groups. METHODS: Data were collected in 26 countries using the Rome IV questionnaire. Forty-nine ordinal variables were used in exploratory factor analysis (EFA) to identify clusters of inter-correlated variables (factors) within the data set. Confirmatory factor analysis with predefined factors of the disorders of gut-brain interaction was compared with the factors in the EFA. Analyses were performed globally, for each geographical region (North and Latin America, Western and Eastern Europe, Middle East, Asia), sex, and age groups (18-34, 35-49, 50-64, ≥65). RESULTS: A total of 54,127 people were included. The EFA identified 10 factors accounting for 57% of the variance: irritable bowel syndrome, constipation, diarrhea, upper gastrointestinal symptoms, globus, regurgitation/retching, chest pain, nausea/vomiting, and 2 right upper quadrant pain factors. Most factors had close correspondence to a Rome IV criteria diagnosis, but notably, functional dysphagia and heartburn symptoms were often included in the same factor and/or in upper gastrointestinal symptoms. Most factors were consistent across geographical regions, sex, and age groups, and compatible to the global results. All prespecified factors in the confirmatory analysis had a loading ≥0.4, indicating validity of the Rome IV criteria. CONCLUSIONS: The results indicate that the Rome IV criteria for irritable bowel syndrome, functional dyspepsia, functional constipation, globus, and biliary pain are globally valid and represent universal diagnostic entities that are similar across sex and age groups.

The Rome Foundation Global Epidemiology study: Research opportunities national and worldwide.

The Rome Foundation embarked on an ambitious multi-year, multinational population-based study to evaluate the prevalence of Rome IV-defined DGBI and their biopsychosocial impact on a worldwide scale. The consistency of the study findings attests to the scientific rigor of this effort, as evident in the publications that resulted from this international study. Dr. Sperber and colleagues report a subanalysis on the Rome IV Global Epidemiology internet survey of the 2012 adults in Israel. These data determined the national prevalence of Rome IV-defined DGBIs, and their associated healthcare utilization and sociodemographic and psychosocial variables. Importantly, they also permitted seamless comparison of the data in the rest of the world. The Israeli study highlights some of the strengths of the Global Epidemiology Study: the 2 respondents had a geographical spread representative of the country. The questionnaire in Israel was available to the participants online in four different languages used by the population in Israel: The database of the study is now available through the Rome Foundation Research Institute for use by academic and industry researchers. This unique gift from the Rome Foundation to the scientific community no doubt will further enhance our understanding of disorders of gut-brain interaction.

A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction.

BACKGROUND AND AIMS: This Rome Foundation Working Team Report reflects the consensus of an international interdisciplinary team of experts regarding the use of behavioral interventions, specifically brain-gut behavior therapies (BGBTs), in patients with disorders of gut-brain interaction (DGBIs). METHODS: The committee members reviewed the extant scientific literature and, when possible, addressed gaps in this literature through the lens of their clinical and scientific expertise. The Delphi method was used to create consensus on the goals, structure, and framework before writing the report. The report is broken into 5 parts: 1) definition and evidence for BGBT, 2) the gut-brain axis as the mechanistic basis for BGBT, 3) targets of BGBTs, 4) common and unique therapeutic techniques seen in BGBT, and 5) who and how to refer for BGBT. RESULTS: We chose to not only review for the reader the 5 existing classes of BGBT and their evidence, but to connect DGBI-specific behavioral targets and techniques as they relate directly, or in some cases indirectly, to the gut-brain axis. In doing so, we expect to increase gastrointestinal providers' confidence in identifying and referring appropriate candidates for BGBT and to support clinical decision making for mental health professionals providing BGBT. CONCLUSIONS: Both gastrointestinal medical providers and behavioral health providers have an opportunity to optimize care for DGBIs through a collaborative integrated approach that begins with an effective patient-provider relationship, thoughtful communication about the brain-gut axis and, when appropriate, a well communicated referral to BGBT.

What elements in the physician-patient relationship (PPR) contribute to patient satisfaction: Development of a short form PPRS-Patient Version (PPRS-Patient SF) Questionnaire.

BACKGROUND: Past research suggests that patient-provider relationships play a crucial role in patient satisfaction with their medical care. However, the essential relationship elements responsible for this effect have not been elucidated and were examined in this study. METHODS: Patients in six gastroenterology clinics at a major medical center completed an anonymous, secure Internet survey about their medical care after a clinic visit. The survey included the validated Satisfaction With Care Scale-37 (SAT-37) and Patient-Physician Relationship Scale (PPRS). Correlations between those scales were calculated, and exploratory factor analysis (EFA) followed by regression analysis was used to create a PPRS Short Form (PPRS-SF) specifically to account for satisfaction with care. KEY RESULTS: 173 patients (114 females and 59 males; mean age 49.2 years) completed the survey. A range of specific patient-doctor relationship aspects on the PPRS substantially influenced the patients' satisfaction scores. These are grouped into five EFA-derived patient perception factors about their physicians: Competence, Connection, Professionalism, Considerateness, and Willingness/ability to make needed outside referrals. A brief 12-item PPRS-SF questionnaire was constructed that explained 63% of the variance in patients' satisfaction with their care. In contrast, the patients' clinical and demographic characteristics had little explanatory value regarding their satisfaction. CONCLUSIONS & INFERENCES: Our findings strongly support the notion that the patient-physician relationship's quality is the principal driver of gastroenterology patients' satisfaction with their care. The new PPRS-SF is a convenient tool for clinicians and healthcare systems to assess the essential relationship factors that ensure satisfied patients.

Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes.

A Review of the Evidence and Recommendations on Communication Skills and the Patient-Provider Relationship: A Rome Foundation Working Team Report.

BACKGROUND & AIMS: Over several decades, changes in health care have negatively impacted meaningful communication between the patient and provider and adversely affected their relationship. Under increasing time pressure, physicians rely more on technology than face-to-face time gathering data to make clinical decisions. As a result, they find it more challenging to understand the illness context and fully address patient needs. Patients experience dissatisfaction and a diminution of their role in the care process. For patients with disorders of gut-brain interaction, stigma leads to greater care dissatisfaction, as there is no apparent structural basis to legitimize the symptoms. Recent evidence suggests that practical communication skills can improve the patient-provider relationship (PPR) and clinical outcomes, but these data are limited. METHODS: The Rome Foundation convened a multidisciplinary working team to review the scientific evidence with the following aims: a) to study the effect of communication skills on patient satisfaction and outcomes by performing an evidence-based review; b) to characterize the influence of sociocultural factors, health care system constraints, patient perspective, and telehealth on the PPR; c) to review the measurement and impact of communication skills training on these outcomes; and d) to make recommendations to improve communication skills training and the PPR. RESULTS: Evidence supports the fact that interventions targeting patient-provider interactions improve population health, patient and provider experience, and costs. Communication skills training leads to improved patient satisfaction and outcomes. The following are relevant factors to consider in establishing an effective PPR: addressing health care system constraints; incorporating sociocultural factors and the role of gender, age, and chronic illness; and considering the changing role of telehealth on the PPR. CONCLUSIONS: We concluded that effective communication skills can improve the PPR and health outcomes. This is an achievable goal through training and system change. More research is needed to confirm these findings.

Psychopharmacologic Therapies for Irritable Bowel Syndrome.

Psychopharmacologic therapies are beneficial in reducing symptoms when treating irritable bowel syndrome (IBS) and other disorders of gut-brain interaction (DGBI). Noradrenaline, serotonin, and dopamine are neurotransmitters of key importance in psychopharmacology and pain-reduction mechanisms. The first-line (tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, selective serotonin reuptake inhibitors) and second-line (atypical antipsychotics, delta-ligand agents, low-dose naltrexone) neuromodulator treatment options are recommended when IBS-associated abdominal pain is of moderate or severe intensity and is persistent. To understand the implementation strategy, the multidimensional clinical profile as a template is used for presenting 3 case scenarios involving painful IBS and DGBI of varying complexity.

A survey of gastroenterologists in the United States on the use of central neuromodulators for treating irritable bowel syndrome.

BACKGROUND: Central neuromodulators are an effective treatment for irritable bowel syndrome (IBS) but may be used less frequently than other therapies. AIMS: To survey gastroenterologists in the United States (US) about their use of neuromodulators in patients with IBS. METHODS: A 23-question survey was distributed to gastroenterologists in the United States. Comparisons in prescribing practices were conducted between (a) gastroenterologists who were "high prescribers" versus "low prescribers" of neuromodulators in patients with IBS and (b) gastroenterologists and "gastroenterology experts" in the use of neuromodulators using descriptive statistics and multivariable logistic regression analyses. RESULTS: The 525 gastroenterologists who were surveyed used neuromodulators for a median range of 21%-30% of their patients with IBS. Neuromodulators were described as extremely/very important in managing IBS by 55% of clinicians. Significant predictors of high-prescribing behaviour were academic versus clinical practice setting (odds ratio [OR] 2.60 [95% CI 1.61-4.20]), disorders of brain-gut interaction focused practice (OR 4.80 [2.60-8.84]), and greater perceived effectiveness of neuromodulators (OR 2.75 [1.30-5.84]). Compared to gastroenterologists, experts prescribed neuromodulators to a higher percentage of their patients with IBS (41%-50% vs 21%-30%; P = 0.019) and more frequently found neuromodulators effective (70% vs 27%; P = 0.003). However, concern about side effects was the most common barrier to neuromodulator use (59%). CONCLUSIONS: The majority of US gastroenterologists believe central neuromodulators are important in treating IBS, and 27% believe they are effective in most patients. High prescribers are in academic practice, focus in IBS and perceive central neuromodulators as effective. Education is needed to improve gastroenterologists' prescribing behaviour.

Deconstructing stigma as a barrier to treating DGBI: Lessons for clinicians.

Stigma, defined as social devaluation based on negative stereotypes toward a particular population, is prevalent within health care and is a common phenomenon in disorders of gut-brain interaction (DGBI). Characteristically, DGBI including functional dyspepsia (FD) lack a structural etiology to explain symptoms, have high psychiatric co-morbidity, and respond to neuromodulators traditionally used to treat psychopathology. As a result, these disorders are frequently and wrongly presumed to be psychiatric and carry a great deal of stigma. Stigma has profound adverse consequences for patients, including emotional distress, medication non-adherence, barriers to accessing care, and increased symptoms. The basis for stigma dates back to the 17th Century concept of mind-body dualism. Patients and health care providers need to understand the factors that promote stigma and methods to ameliorate it. In this minireview, we address the data presented in Yan et al.'s (Neurogastroenterol Motil, 2020, e13956). We offer concrete solutions for clinicians to mitigate the impact of stigma to optimize treatment adherence and clinical outcomes for patients with DGBI.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Preliminary development and validation of the Patient-Physician Relationship Scale for physicians for disorders of gut-brain interaction.

BACKGROUND: An effective patient-physician relationship (PPR) is essential to the care of patients with irritable bowel syndrome (IBS). After developing a PPR questionnaire for patients, we sought to develop and validate an IBS-specific instrument to measure physician expectations of the PPR. METHODS: We conducted focus groups about PPRs among 15 clinicians who treat patients with IBS from community and academic centers. Qualitative analysis was used to generate the Patient-Physician Relationship Scale -Physician RESULTS: The PPRS-Physician contained 35 questions pertaining to interpersonal and psychosocial features considered desirable or undesirable in a relationship with IBS patients. 1113 physicians (22%) completed the survey. Physicians were predominantly middle-aged (mean = 55.1 years), male (85.0%), white (74.5%), and practiced primarily within group settings (61.6%), with an average of 25.7% of their patients having IBS. Factor analysis revealed three relevant factors: interfering attributes, positive attributes, and personal connection. The scale ranged from possible 0 to 100 (mean = 83.8; SD = 8.38). Cronbach's alpha reliability measure of the scale was 0.938, indicating high internal consistency. There was a significant moderate, positive correlation between JSPE and the PPRS (P < 0.001, r = 0.488), establishing concurrent validity. CONCLUSIONS: We describe the development and validation of the first questionnaire to measure physician expectations of the PPR. This instrument can be used clinically, and for future studies on physician communication.

Functional gastrointestinal disorders: advances in understanding and management.

Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut-brain interaction (via the gut-brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut-brain interaction. Psychological comorbidity is common; however, whether or not this predates, or is driven by, symptoms is not clear. Patients with functional gastrointestinal disorders can feel stigmatised, and often this diagnosis is not communicated effectively by physicians, nor is education provided. Prompt identification and treatment of these conditions is crucial as they have a considerable impact on health-care systems and society as a whole because of repeated consultations, unnecessary investigations and surgeries, prescriptions and over-the-counter medicine use, and impaired health-related quality of life and ability to work. Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.

Antidepressants in inflammatory bowel disease.

Gut-brain dysregulation has been recognized by the scientific community as being crucial to the understanding of chronic gastrointestinal conditions, and this has translated into the practice of a newly established discipline, psychogastroenterology. Along with psychotherapy, antidepressants (a subtype of central neuromodulators) have been proposed as treatments for gut-brain disorders that might benefit both psychological and gastrointestinal health. Antidepressants have been found to be effective for the treatment of comorbid anxiety and depression, pain and impaired sleep. Although the efficacy of antidepressants is well established in disorders of gut-brain interaction (DGBI), evidence is only now emerging in IBD. This Perspective discusses the use of antidepressants in DGBI and IBD, focusing on how what we have learnt about the role of antidepressants in DGBI could be applied to help optimize the management of IBD.

Improving Patient-Provider Relationships to Improve Health Care.

Changes in our health care system have posed challenges for the patient-provider relationship (PPR) and may have negative consequences. For the clinician, due to lower reimbursements from third party payers, and increased administrative tasks such as the electronic medical record (EMR) and certification requirements, clinic visit time is now one-fifth that of decades ago. Clinicians may order diagnostic studies and imaging as a substitute for face to face time as it is seen to save time and increase relative value units (RVUs). As a result, the medical interview is very abbreviated, and the physical examination is disappearing. This occurs at the expense of the physician-patient relationship. Now there is limited time to gather relevant information, to understand the context of the illness, and address patient needs. For the clinician there is reduced satisfaction, loss of the meaningfulness of caring for patients, and possibly increased risk for burnout, and malpractice. This may lead to negative attitudes and behaviors toward patients, particularly for those with nonstructural diagnoses (eg, disorders of gut-brain interaction) which are given lower priority than those with acute or structural illness. In turn, patients experience a diminution in their role in the relationship and respond to adverse clinician behaviors with a lack of connection, frustration, and at times self-blame and stigmatization. To reverse this downward trend and re-establish an effective PPR changes are needed: 1) improving educational methods to provide skills to enhance patient-centered care, 2) incentivizing educators who teach and clinicians who practice patient-centered care, and 3) research support to demonstrate successful outcomes in satisfaction, adherence and clinical outcomes.