Factors That Predict Magnitude, Timing, and Persistence of Placebo-Like Response in Patients With Irritable Bowel Syndrome.

BACKGROUND AND AIMS: Placebo response impedes the development of novel irritable bowel syndrome (IBS) therapies and the interpretability of randomized clinical trials. This study sought to characterize the magnitude, timing, and durability of IBS symptom relief in patients undergoing a non-drug placebo-like control. METHODS: One hundred forty-five Rome III-diagnosed patients (80% F, M age = 42 years) were assigned to education/nondirective support delivered over a 10-week acute phase. Treatment response was based on the IBS version of the Clinical Global Improvement Scale completed 2 weeks after treatment ended. Candidate predictors were assessed at baseline (eg, emotion regulation, pain catastrophizing, distress, neuroticism, stress, somatization, gastrointestinal-specific anxiety) or clinically relevant points during treatment (patient-provider relationship, treatment expectancy/credibility). RESULTS: Midtreatment response was associated with lower levels of stress and somatization at baseline and greater patient-provider agreement on treatment tasks (P < .001). Treatment response was associated with baseline gastroenterologist-rated IBS severity, anxiety, ability to reappraise emotions to reduce their impact [cognitive reappraisal], and agreement that provider and patient shared goals from provider perspective (P < .001). The day-to-day ability to reappraise emotions at baseline distinguished rapid from delayed placebo responders (P = .011). CONCLUSION: Patient beliefs (eg, perceived stress, cognitive reappraisal) impacted the magnitude, timing, and persistence of placebo response measured at midway point of acute phase and 2 weeks after treatment discontinuation. Baseline beliefs that patients could alter the impact of stressful events by rethinking their unpleasantness distinguished rapid vs delayed placebo responders. Collaborative agreement between doctor and patient around shared tasks/goals from the clinician perspective predicted placebo response.

Cognitive Behavioral Therapy for Chronic Pelvic Pain: What Is It and Does It Work?

PURPOSE: Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome in women and men and chronic prostatitis/chronic pelvic pain syndrome in men, is a common, often disabling urological disorder that is neither well understood nor satisfactorily treated with medical treatments. The past 25 years have seen the development and validation of a number of behavioral pain treatments, of which cognitive behavioral therapy (CBT) is arguably the most effective. CBT combines strategies of behavior therapy, which teaches patients more effective ways of behaving, and cognitive therapy, which focuses on correcting faulty thinking patterns. As a skills-based treatment, CBT emphasizes "unlearning" maladaptive behaviors and thoughts, and replacing them with more adaptive ones that support symptom self-management. MATERIALS AND METHODS: This review describes the rationale, technical procedures, and empirical basis of CBT. RESULTS: While evidence supports CBT for treatment-refractory chronic pain disorders, there is limited understanding of why or how CBT might work, for whom it is most beneficial, or the specific UCPPS symptoms (eg, pain, urinary symptoms) it effectively targets. This is the focus of EPPIC (Easing Pelvic Pain Interventions Clinical Research Program), a landmark NIH trial examining the efficacy of low-intensity, home-based CBT for UCPPS relative to a nonspecific comparator featuring self-care recommendations of AUA guidelines. CONCLUSIONS: Systematic efforts to increase both the efficiency of CBT and the way it is delivered (eg, home-based treatments) are critical to scaling up CBT, optimizing its therapeutic potential, and reducing the public health burden of UCPPS.

Study protocol and methods for Easing Pelvic Pain Interventions Clinical Research Program (EPPIC): a randomized clinical trial of brief, low-intensity, transdiagnostic cognitive behavioral therapy vs education/support for urologic chronic pelvic pain syndrome (UCPPS).

BACKGROUND: Urologic chronic pelvic pain syndrome (UCPPS) encompasses several common, costly, diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome that are poorly understood and inadequately treated with conventional medical therapies. Behavioral strategies, recommended as a first-line treatment for managing symptoms, are largely inaccessible, time and labor intensive, and technically complex. The Easing Pelvic Pain Interventions Clinical Research Program (EPPIC) is a clinical trial examining the efficacy of low-intensity cognitive behavioral therapy (Minimal Contact CBT or MC-CBT) for UCPPS and its durability 3 and 6 months post treatment. Additional aims include characterizing the operative processes (e.g., cognitive distancing, context sensitivity, coping flexibility, repetitive negative thought) that drive MC-CBT-induced symptom relief and pre-treatment patient variables that moderate differential response. METHODS: UCPPS patients (240) ages 18-70 years, any gender, ethnicity, and race, will be randomized to 4-session MC-CBT or a credible, non-specific education comparator (EDU) that controls for the generic effects from simply going to treatment. Efficacy assessments will be administered at pre-treatment, 2 weeks, and 3 and 6 months post treatment-week acute phase. A novel statistical approach applied to micro-analytic mediator assessment schedule will permit the specification of the most effective CBT component(s) that drive symptom relief. DISCUSSION: Empirical validation of a low-intensity self-management therapy transdiagnostic in scope has the potential to improve the health of chronic pelvic pain patients refractory to medical therapies, reduce social and economic costs, conserve health care resources, as well as inform evidence-based practice guidelines. Identification of change mechanisms and moderators of treatment effects can provide proactive patient-treatment matching fundamental to goals of personalized medicine. TRIAL REGISTRATION: Clinicaltrials.gov NCT05127616. Registered on 9/19/21.

Cognitive flexibility improves in cognitive behavioral therapy for irritable bowel syndrome but not nonspecific education/support.

This study tested the novel hypothesis that CBT-treated IBS patients who learn to self-manage painful GI symptoms by targeting rigid cognitive style show improvement in cognitive flexibility, GI symptoms (e.g., abdominal pain), and quality of life. Participants included 130 Rome-III diagnosed IBS patients (M age = 40.3, F = 83%) with moderate-to-severe symptoms randomly assigned to either cognitive behavioral therapy (CBT; N = 86) or a nonspecific education/support (EDU) comparator (N = 44). Participants completed an assessment battery at baseline and post-treatment 2 weeks after 10-week acute treatment phase. Measures included cognitive flexibility, psychological flexibility, emotion regulation strategies, IBS symptom severity, quality of life (QOL), and distress. CBT but not EDU patients showed significant GI sympton improvement from baseline to post-treatment in cognitive flexibility. For CBT patients, changes in cognitive flexibility were significantly associated with changes in IBS symptom severity, abdominal pain, and IBS QOL. Neither condition showed significant changes in psychological flexibility (Acceptance and Action Questionnaire-II) or use of emotion regulation strategies (Emotion Regulation Questionnaire). The ability to self-manage painful IBS symptoms refractory to conventional medical and dietary treatments is related to the ability to respond flexibly across shifting contexts using cognitive change procedures featured in CBT for IBS.

Do I really have to do my homework? The role of homework compliance in cognitive behavioral therapy for irritable bowel syndrome.

Treatment guidelines identify cognitive behavioral therapy (CBT) as a treatment of choice for irritable bowel syndrome (IBS). As a learning-based treatment, homework assignments are regarded as important for optimizing outcomes for CBT-treated patients. However, their actual benefit for IBS is unknown. This study examined whether homework completion corresponds with immediate and sustained treatment response in IBS patients enrolled in CBT treatment. Subjects were 358 IBS patients receiving clinic-based CBT (10 session), home-based CBT (4 session), or a 4 session, non-specific IBS education comparator as part of a large NIH trial. Homework completion was rated by clinician at each session. IBS symptom improvement was measured with the Clinician Global Improvement Scale at treatment week 5, post-treatment (week 12), and at follow-ups (weeks 22, 34, 46, 62). Homework completion rates over the 10-week acute phase corresponded with greater IBS symptom improvement and patient satisfaction at post-treatment. Early treatment homework completion did not predict early treatment response. Contrary to expectations, homework compliance rates were not greater among in-clinic session patients than home-based patients. Data lend empirical support to the clinical value of homework in teaching patients how to self-manage painful GI symptoms refractory to conventional medical and dietary therapies.

Durability and Decay of Treatment Benefit of Cognitive Behavioral Therapy for Irritable Bowel Syndrome: 12-Month Follow-Up.

BACKGROUND: There is a need for safe and effective IBS treatments that provide immediate and sustained improvement of IBS symptoms, particularly among more severe patients. The aim was to assess long-term clinical response of cognitive behavioral therapy (CBT) with reference to IBS education. METHODS: A total of 436 Rome III-diagnosed IBS patients (80% F, M age = 41 years) were randomized to: 4 session home-based CBT (minimal contact (MC-CBT)), 10 session clinic-based CBT (standard (S-CBT)), or 4 session IBS education (EDU). Follow-up occurred at 2 weeks and 3, 6, 9, and 12 months following treatment completion. Treatment response was based a priori on the Clinical Global Improvement Scale (global IBS symptom improvement) and IBS Symptom Severity Scale (IBS-SSS). RESULTS: Post-treatment CGI gains were generally maintained by MC-CBT patients at quarterly intervals through 12-month follow-up with negligible decay. For MC-CBT and S-CBT, 39 and 33% of respondents maintained treatment response at every follow-up assessment. The corresponding percent for EDU was 19%, which was significantly lower (p < 0.05) than for the CBT groups. On the IBS-SSS, therapeutic gains also showed a pattern of maintenance with trends towards increased efficacy over time in all conditions, with the mean unit reductions between baseline and follows-up being approximately -76 at immediate and approximately -94 at 12 months (-50 = clinically significant). CONCLUSIONS: For treatment-refractory IBS patients, home- and clinic-based CBT resulted in substantial and enduring relief of multiple IBS symptoms that generally extended to 12-month post treatment.

Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome.

BACKGROUND & AIMS: There is an urgent need for safe treatments for irritable bowel syndrome (IBS) that relieve treatment-refractory symptoms and their societal and economic burden. Cognitive behavior therapy (CBT) is an effective treatment that has not been broadly adopted into routine clinical practice. We performed a randomized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education. METHODS: We performed a prospective study of 436 patients with IBS, based on Rome III criteria, at 2 tertiary centers from August 23, 2010, through October 21, 2016. Subjects (41.4 ± 14.8 years old; 80% women) were randomly assigned to groups that received the following: standard-CBT (S-CBT, n = 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training), or 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n = 145), in which patients received home-study materials covering the same procedures as S-CBT), or 4 sessions of IBS education (EDU, n = 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise. The primary outcome was global improvement of IBS symptoms, based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation. Efficacy data were collected 2 weeks, 3 months, and 6 months after treatment completion. RESULTS: A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment (61.0% based on ratings by patients and 55.7% based on ratings by gastroenterologists) than those receiving EDU (43.5% based on ratings patients and 40.4% based on ratings by gastroenterologists) (P < .05). Gastrointestinal symptom improvement, rated by gastroenterologists, 6 months after the end of treatment also differed significantly between the MC-CBT (58.4%) and EDU groups (44.8%) (P = .05). Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms. Patients tended to be more satisfied with CBT vs EDU (P < .05) based on immediate posttreatment responses to the Client Satisfaction Questionnaire. Symptom improvement was not significantly related to concomitant use of medications. CONCLUSIONS: In a randomized controlled trial, we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education. Clinicaltrials.gov no.: NCT00738920.

(Can't Get No) Patient Satisfaction: The Predictive Power of Demographic, GI, and Psychological Factors in IBS Patients.

GOALS: The goal of this study is to assess: (1) the relative contribution of patient factors to satisfaction ratings in irritable bowel syndrome (IBS) patients and (2) the relationship between patient satisfaction (PS) and the number of diagnostic tests patients underwent prior to receiving IBS diagnosis. BACKGROUND: Although PS is regarded as an important indicator of quality of care, little is known about its determinants. STUDY: A total of 448 Rome III-diagnosed patients (M age=41 y; 79% F), whose GI symptoms were at least moderate in severity completed patient-reported outcome measures as part of pretreatment evaluation of an NIH-funded clinical trial. PS was measured with the 11-point Hospital Consumer Assessment of Healthcare Providers and Systems global rating scale modified to assess for IBS treatments. A series of multiple regression analyses were conducted for demographic, IBS-specific, general physical health, and psychological predictors before running a final model of significant predictors from each domain. RESULTS: The final regression model was significant, F6,419=6.34, P<0.001, R=0.08, with race, insurance, number of diagnostic tests, and lower neuroticism predicting PS. Medical tests were rendered nonsignificant when history of seeking care from a gastroenterologist was introduced into the equation. CONCLUSIONS: Contrary to hypotheses, neither the IBS symptom severity nor quality of life impairment predicted PS. Patient factors such as a neurotic personality style and sociodemographic profile had a significant but modest impact on PS. Pattern of regression analyses suggests that patients may turn to their gastroenterologist for testing for reassurance, which may in the long-term fuel demand for more testing.

Negative aspects of close relationships are more strongly associated than supportive personal relationships with illness burden of irritable bowel syndrome.

OBJECTIVE: This study assessed the relative magnitude of associations between IBS outcomes and different aspects of social relationships (social support, negative interactions). METHOD: Subjects included 235 Rome III diagnosed IBS patients (M age=41yrs, F=78%) without comorbid GI disease. Subjects completed a testing battery that included the Interpersonal Support Evaluation List (Social Support or SS), Negative Interaction (NI) Scale, IBS Symptom Severity Scale (IBS-SSS), IBS-QOL, BSI Depression, STAI Trait Anxiety, SOMS-7 (somatization), Perceived Stress Scale, and a medical comorbidity checklist. RESULTS: After controlling for demographic variables, both SS and NI were significantly correlated with all of the clinical variables (SS r's=.20 to .36; NI r's=.17 to .53, respectively; ps<.05) save for IBS symptom severity (IBS-SSS). NI, but not SS, was positively correlated with IBS-SSS. After performing r-to-z transformations on the correlation coefficients and then comparing z-scores, the correlation between perceived stress, and NI was significantly stronger than with SS. There was no significant difference between the strength of correlations between NI and SS for depression, somatization, trait anxiety, and IBSQOL. A hierarchical linear regression identified both SS and NI as significant predictors of IBS-QOL. CONCLUSIONS: Different aspects of social relationships - support and negative interactions - are associated with multiple aspects of IBS experience (e.g. stress, QOL impairment). Negative social relationships marked by conflict and adverse exchanges are more consistently and strongly related to IBS outcomes than social support.

Type, rather than number, of mental and physical comorbidities increases the severity of symptoms in patients with irritable bowel syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) has significant mental and physical comorbidities. However, little is known about the day-to-day burden these comorbidities place on quality of life (QOL), physical and mental function, distress, and symptoms of patients. METHODS: We collected cross-sectional data from 175 patients with IBS, which was diagnosed on the basis of Rome III criteria (median age, 41 years; 78% women), who were referred to 2 specialty care clinics. Patients completed psychiatric interviews, a physical comorbidity checklist, the IBS Symptom Severity Scale, the IBS-QOL instrument, the Brief Symptom Inventory, the abdominal pain intensity scale, and the Short Form-12 Health Survey. RESULTS: Patients with IBS reported an average of 5 comorbidities (1 mental, 4 physical). Subjects with more comorbidities reported worse QOL after adjusting for confounding variables. Multiple linear regression analyses indicated that comorbidity type was more consistently and strongly associated with illness burden indicators than disease counts. Of 10,296 possible physical-mental comorbidity pairs, 6 of the 10 most frequent dyads involved specific conditions (generalized anxiety, depression, back pain, agoraphobia, tension headache, and insomnia). These combinations were consistently associated with greater illness and symptom burdens (QOL, mental and physical function, distress, more severe symptoms of IBS, and pain). CONCLUSIONS: Comorbidities are common among patients with IBS. They are associated with distress and reduced QOL. Specific comorbidities are associated with more severe symptoms of IBS.

Rapid response to cognitive behavior therapy predicts treatment outcome in patients with irritable bowel syndrome.

BACKGROUND & AIMS: Cognitive behavior therapy (CBT) is an empirically validated treatment for irritable bowel syndrome (IBS), yet it is unclear for whom and under what circumstances it is most effective. We investigated whether patients who achieved a positive response soon after CBT onset (by week 4), termed rapid responders (RRs), maintain treatment gains compared with non-rapid responders. We also characterized the psychosocial profile of RRs on clinically relevant variables (eg, health status, IBS symptom severity, distress). METHODS: The study included 71 individuals (age, 18-70 y) whose IBS symptoms were consistent with Rome II criteria and were of at least moderate severity. Patients were assigned randomly to undergo a wait list control; 10 weekly 1-hour sessions of CBT; or four 1-hour CBT sessions over 10 weeks. RRs were classified as patients who reported adequate relief of pain, adequate relief of bowel symptoms, and a decrease in total IBS severity scores of 50 or greater by week 4. RESULTS: Of patients undergoing CBT, 30% were RRs; 90% to 95% of the RRs maintained gains at the immediate and 3-month follow-up examinations. Although the RRs reported more severe IBS symptoms at baseline, they achieved more substantial, sustained IBS symptom reduction than non-rapid responders. Both dosages of CBT had comparable rates of RR. CONCLUSIONS: A significant proportion of IBS patients treated with CBT have a positive response within 4 weeks of treatment; these patients are more likely to maintain treatment gains than patients without a rapid response. A rapid response is not contingent on the amount of face-to-face contact with a clinician.

Self-administered cognitive behavior therapy for moderate to severe irritable bowel syndrome: clinical efficacy, tolerability, feasibility.

BACKGROUND & AIMS: Given the limitations of conventional therapies and restrictions imposed on newer pharmacologic agents, there is an urgent need to develop efficacious and efficient treatments that teach patients behavioral self-management skills for relieving irritable bowel syndrome (IBS) symptoms and associated problems. METHODS: Seventy-five Rome II diagnosed IBS patients (86% female) without comorbid gastrointestinal disease were recruited from local physicians and the community and randomized to either 2 versions of cognitive behavior therapy (CBT) (10-session, therapist-administered CBT vs 4-session, patient-administered CBT) or a wait list control (WLC) that controlled for threats to internal validity. Final assessment occurred 2 weeks after the 10-week treatment phase ended. Outcome measures included adequate relief from pain and bowel symptoms, global improvement of IBS symptoms (CGI-Improvement Scale), IBS symptom severity scale (IBS SSS), quality of life (IBSQOL), psychological distress (Brief Symptom Inventory), and patient satisfaction (Client Satisfaction Scale). RESULTS: At week 12, both CBT versions were significantly (P < .05) superior to WLC in the percentage of participants reporting adequate relief (eg, minimal contact CBT, 72%; standard CBT, 60.9%; WLC, 7.4%) and improvement of symptoms. CBT-treated patients reported significantly improved quality of life and IBS symptom severity but not psychological distress relative to WLC patients (P < .0001). CONCLUSIONS: Data from this pilot study lend preliminary empirical support to a brief patient-administered CBT regimen capable of providing short-term relief from IBS symptoms largely unresponsive to conventional therapies.

How does cognitive behavior therapy for irritable bowel syndrome work? A mediational analysis of a randomized clinical trial.

BACKGROUND AND AIMS: Although multiple clinical trials support the efficacy of psychological treatments for reducing irritable bowel syndrome (IBS) symptoms, the mechanisms responsible for symptomatic improvement are unknown. One hypothesis is that psychological treatments work by alleviating comorbid psychological distress implicated in the worsening of bowel symptoms and quality of life. An alternative hypothesis assumes that changes in distress are not strictly a cause but a consequence of IBS that will decrease with symptomatic improvement. METHODS: We evaluated these 2 hypotheses by applying structural equation modeling (SEM) to the data set of a large number (n = 147) of Rome II diagnosed participants randomized to CBT, psychoeducation, or wait list. Per Rome guidelines, the primary end point was global improvement of gastrointestinal (GI) symptoms measured 2 weeks after a 10-week regimen. Secondary end points were distress and quality of life (QOL). RESULTS: SEM analyses lend support to a model in which CBT is associated with improvements in IBS symptoms, but that therapeutic gains do not depend on changes in patients' overall level of psychological distress. Symptom severity, but not clinical status (pain catastrophizing, predominant bowel habits, symptom duration, abuse, diagnosable psychiatric disorder) or relevant sociodemographic variables (eg, gender, age), moderated treatment outcome. CONCLUSION: CBT has a direct effect on global IBS symptom improvement independent of its effects on distress. Improvement in IBS symptoms is associated with improvements in the QOL, which may lower distress. Symptom improvements are not moderated by variables reflecting the mental well-being of IBS patients.

Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety.

This study sought to identify brain regions that underlie symptom changes in severely affected IBS patients undergoing cognitive therapy (CT). Five healthy controls and 6 Rome II diagnosed IBS patients underwent psychological testing followed by rectal balloon distention while brain neural activity was measured with O-15 water positron emission tomography (PET) before and after a brief regimen of CT. Pre-treatment resting state scans, without distention, were compared to post-treatment scans using statistical parametric mapping (SPM). Neural activity in the parahippocampal gyrus and inferior portion of the right cortex cingulate were reduced in the post-treatment scan, compared to pre-treatment (x, y, z coordinates in MNI standard space were -30, -12, -30, P=0.017; 6, 34, -8, P=0.023, respectively). Blood flow values at these two sites in the controls were intermediate between those in the pre- and post-treatment IBS patients. Limbic activity changes were accompanied by significant improvements in GI symptoms (e.g., pain, bowel dysfunction) and psychological functioning (e.g., anxiety, worry). The left pons (-2, -26, -28, P=0.04) showed decreased neural activity which was correlated with post-treatment anxiety scores. Changes in neural activity of cortical-limbic regions that subserve hypervigilance and emotion regulation may represent biologically oriented change mechanisms that mediate symptom improvement of CT for IBS.