Cognitive factors affect treatment response to medical and psychological treatments in functional bowel disorders.

OBJECTIVES: For clinical trials in functional bowel disorders (FBD), the definition of a responder, one who meets the predefined criteria for a clinical response, is needed. Factors that determine clinical response aside from treatment itself are unknown. The aim of this study was to determine what baseline and post-treatment factors affect treatment response. METHODS: Females (n=397) with FBD entering a 12-week, four-arm, randomized NIH treatment trial (desipramine (DES), CBT, pill placebo, and education) were studied at baseline and after treatment. Demographic, clinical, psychosocial, and physiological variables were considered in the analysis. A responder was defined as a patient obtaining a score>3.5 on an averaged eight-item, five-point satisfaction-with-treatment questionnaire. Baseline and post-treatment logistic regressions were performed for each treatment condition to predict the responder outcome variable. RESULTS: Similar cognitive features predisposed participants to treatment response across the treatment conditions: sense of control over the condition, positive relationship with therapist or study coordinator, confidence in treatment, improvement in maladaptive cognitions, and quality of life during treatment. Demographic and clinical variables studied were not predictive. Some treatment-specific effects predicting responder status were noted, including a reduction in stool frequency with DES treatment and lack of abuse history in the placebo group. CONCLUSIONS: For medication, psychological, and placebo treatment in FBD, satisfaction with treatment depends on cognitive factors of confidence in treatments, perceived control over illness and symptoms, and reduction in negative cognitions related to symptom experience. Addressing these issues among patients with FBD may enhance treatment response to a variety of treatments.

Irritable bowel syndrome subtypes defined by Rome II and Rome III criteria are similar.

BACKGROUND: The implications of the Rome III recommendations to change the irritable bowel syndrome (IBS) subtype criteria for stool pattern are unknown. AIM: (1) Determine the level of agreement between Rome II and Rome III subtypes and (2) compare the behaviors of Rome II and Rome III subtypes over time. METHODS: Female patients (n=148) with Rome II defined IBS were prospectively tracked over 5 consecutive 3-month periods. At baseline, bowel habit reports on questionnaires were used to subclassify patients into Rome II and Rome III subtypes. Over the subsequent 15 months, bowel habit reports on diary cards were used to subclassify patients based on previously derived surrogate criteria into Rome II and Rome III IBS subtypes. RESULTS: The level of agreement between Rome II and Rome III subtype assignments was quite high (86.5%; kappa 0.79). The behavior of Rome II and Rome III subtypes over time was also similar in terms of subtype prevalence, subtype stability, and the proportion of subjects who met criteria for alternating irritable bowel syndrome. CONCLUSIONS: Rome II and Rome III IBS subtypes are in high agreement and behave similarly over time. Therefore, studies that used Rome II subtype criteria and studies that will use Rome III criteria will define comparable populations.

Not all side effects associated with tricyclic antidepressant therapy are true side effects.

BACKGROUND & AIMS: Patients with functional gastrointestinal disorders treated with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it is unclear whether these are drug side effects or reflect a behavioral tendency to report symptoms. We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms. METHODS: Female patients in a multicenter National Institutes of Health trial for functional bowel disorders completed a 15-item symptom questionnaire at baseline (before randomization), 2 weeks after they were given desipramine (n = 81) or placebo (n = 40), and at study completion (12 weeks). Patients were asked about the severity and frequency of 15 symptoms. Results were analyzed from 57 patients given desipramine who completed the questionnaires. RESULTS: Symptoms reported as side effects to have occurred more frequently and also worsened at week 2 in the group given desipramine included dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and flushing. Symptoms that did not change in severity or showed improvement at week 2 in the group given desipramine included morning tiredness, nausea, blurred vision, headaches, appetite reduction, and trouble sleeping. Psychologic distress but not desipramine blood level correlated with symptom reporting. CONCLUSIONS: Most symptoms often attributed to side effects of desipramine were present before treatment; only a few, related to anticholinergic effects, worsened 2 weeks after treatment, suggesting that most so-called side effects were not associated specifically with desipramine use. Such symptoms might instead be associated with psychologic distress.

Characterization of health related quality of life (HRQOL) for patients with functional bowel disorder (FBD) and its response to treatment.

BACKGROUND AND AIMS: Assessing health related quality of life (HRQOL) is becoming more important in research and clinical care. However, little information is available on the performance of HRQOL questionnaires for the functional bowel disorders (FBD). The aims of this study were to (a) understand the performance of the Sickness Impact Profile (SIP) and IBS-QOL for the functional bowel disorders at baseline and after treatment, (b) determine which HRQOL subscales best improve with treatment, (c) determine clinically meaningful improvement, and (d) determine the predictors of HRQOL at baseline and in response to treatment. METHODS: Women with moderate to severe FBD were evaluated using both medical (desipramine vs placebo) and psychological (cognitive-behavioral therapy vs education) treatments. Clinical and psychosocial questionnaires along with the SIP and IBS-QOL were given at baseline and after 12-wk treatment. RESULTS: (a) Patients with FBD experience functional limitations in social interactions, home management, and recreational activities, respond emotionally to the pain, feel helpless, out of control, depressed, and irritable, and perceive restrictions in lifestyle relating to toilet accessibility, and eating; (b) HRQOL is not different among the FBD diagnoses or IBS subgroups; (c) the IBS-QOL is more responsive to treatment than the SIP; (d) meaningful clinical improvement is 2.8 points for SIP and 14 for IBS-QOL; and (e) improvement is demonstrated primarily in psychosocial rather than physical domains. In addition, we found that expectation of benefit is greater for taking a pill over a psychological intervention, and the predictive effects of abuse history and pain on outcome is mediated by psychosocial factors. CONCLUSIONS: The data support the value of the IBS-QOL over the SIP, and provide new information on the profile of impairment in FBD, and the ways in which medical and psychological treatments produce improvement in HRQOL.

Impact of life events and difficulties on the mental health of Chinese immigrant women.

This study examined the life events and difficulties inherent to the immigration process and the sources of social support that influenced mental health. A six-month longitudinal study, utilizing a detailed semi-structured interview protocol and standardized questionnaires, was conducted with a group of Chinese women who had migrated to Canada with their spouses in the last decade. All of the women and all of their spouses experienced major downward mobility. Correspondingly, the most frequent negative life event was employment-related and the most frequent difficulty was the financial strain of living below the poverty line, factors which significantly predicted the women's mental health. Social support had neither a main effect on mental health nor a buffer effect on the relationship between life events and difficulties and mental health. Implications for immigration and settlement policy are discussed.

Gender, age, society, culture, and the patient's perspective in the functional gastrointestinal disorders.

Patients with functional gastrointestinal disorders (FGID) often experience emotional distress, a perceived lack of validation, and an unsatisfactory experience with health care providers. A health care provider can provide the patient with a framework in which to understand and legitimize their symptoms, remove self-doubt or blame, and identify factors that contribute to symptoms that the patient can influence or control. This framework can be strengthened with the consideration of various important factors that impact FGID but are often overlooked. These include gender, age, society, culture, and the patient's perspective. There is evidence for sex- and gender-related differences in FGID, particularly irritable bowel syndrome (IBS). Whereas the majority of FGID, including IBS, bloating, constipation, chronic functional abdominal pain, and pelvic floor dysfunction, are more prevalent in women than men, functional esophageal and gastroduodenal disorders do not appear to vary by gender. Limited studies suggest that sex differences in visceral perception, cardioautonomic responses, gastrointestinal motility, and brain activation patterns to visceral stimuli exist in IBS. Gender differences in social factors, psychological symptoms, and response to psychological treatments have not been adequately studied. However, there appears to be a greater clinical response to serotonergic agents developed for IBS in women compared to men. The impact of social and cultural factors on the meaning, expression, and course of FGID are important. The prevalence of IBS appears to be lower in non-Western than Western countries. Although further studies are needed, the existing literature suggests that they are important to consider from both research and clinical perspectives.

Cognitive-behavioral treatment of irritable bowel syndrome.

There is increasing evidence that supports the view that irritable bowel disorder (IBS) is a disorder of brain-gut function. Cognitive-behavioral therapy (CBT) has received increased attention in light of this recent shift in the conceptualization of IBS. This review has two main aims. The first is to provide a critical review of controlled trials on CBT for IBS. The second is to discuss ways of further developing CBT interventions that are more clinically relevant and meaningful to health care providers and individuals with a diagnosis of IBS. A theme from a CBT intervention will be presented to illustrate how CBT interventions can be incorporated within a larger social context. A review of CBT for IBS lends some limited support for improvement in some IBS symptoms and associated psychosocial distress. This conclusion needs to be expressed with some caution, however, in light of many methodological shortcomings including small sample sizes, inadequate control conditions and failure to identify primary versus secondary outcome measures. In addition, future studies will need to further develop more relevant CBT protocols that more fully integrate the patient's perspective and challenge social cognitions about this stigmatized disorder.

A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is subtyped as IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C) based on Rome II guidelines. The remaining group is considered as having mixed IBS (IBS-M). There is no standard definition of an alternator (IBS-A), in which bowel habit changes over time. Our aim was to use Rome II criteria to prospectively assess change in bowel habit for more than 1 year to understand IBS-A. METHODS: Female patients (n=317) with IBS entering a National Institutes of Health treatment trial were studied at baseline with questionnaires and 2-week daily diary cards of pain and stool frequency and consistency. Studies were repeated at the end of treatment (3 months) and at four 3-month intervals for one more year. Algorithms to classify subjects into IBS-D, IBS-C, and IBS-M groups used diary card information and modified Rome II definitions. Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures. RESULTS: At baseline, 36% had IBS-D, 31% IBS-M, and 34% IBS-C. Except for stool frequency, there were no differences between groups. While the proportion of subjects in each subgroup remained the same over the year, most individuals (more than 75%) changed to either of the other 2 subtypes at least once. IBS-M was the least stable (50% changed out by 12 weeks). Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably, only 29% switched between the IBS-D and IBS-C subtypes over the year. CONCLUSIONS: While the proportion of subjects in each of the IBS subtypes stays the same, individuals commonly transition between subtypes, particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period.

Clinical response to tricyclic antidepressants in functional bowel disorders is not related to dosage.

BACKGROUND: As shown in the per protocol analysis of a recent randomized, controlled trial, when tolerated, Desipramine (DES) is effective over placebo (PLA) in treating moderate-to-severe functional bowel disorders (FBD). Clinical experience suggests that the benefit from tricyclic antidepressants (TCA) in FBD can be achieved at doses lower than those used to treat major depression. Within psychiatry, when using higher dosage of TCAs, plasma levels can be used to adjust daily dosage to optimize a treatment response. However, in FBD, it is not known whether plasma levels at the lower dosage are similarly related to a clinical response. AIM: To determine in treating FBD, whether DES blood levels or dose taken can predict a clinical response. METHODS: As part of a study of 12 wk of antidepressant and psychological treatment in 431 patients with FBD at UNC and U of Toronto, we studied those participants who completed treatment (per protocol analysis) taking DES (N = 97, dose 50-150 mg/day) or pill placebo (PLA) (N = 55 1-3 pills/day). The primary outcome measure was defined as a composite score (Satisfaction with Treatment, McGill Pain Questionnaire, Global Well-being, and IBS-QOL). The composite score was correlated with: (i) DES plasma levels at week 6, and (ii) number of pills taken over the duration of the 12-wk treatment period. In addition, we also compared DES dose with DES plasma levels. RESULTS: There was a modest correlation between mean DES dose at weeks 5 and 6 and DES blood level at week 6 (R = 0.2 p < 0.07). However, there were no significant correlations between the composite score either with DES dose or with DES blood levels. CONCLUSIONS: Detectable blood levels of DES are associated with a clinical response in FBD. However, with dosages up to 150 mg, there is no relationship between total dose or plasma level and the clinical response.

Cognitive change in patients undergoing hypnotherapy for irritable bowel syndrome.

OBJECTIVE: Impaired quality of life and psychological distress are common in irritable bowel syndrome (IBS) and may be associated with unhelpful cognitions. Hypnotherapy (HT) is effective in improving both symptoms and quality of life in patients with IBS, and this study was designed to determine whether this improvement is reflected in cognitive change using a validated scale recently developed for use in such patients. METHOD: A total of 78 IBS patients completed a validated symptom-scoring questionnaire, the Hospital Anxiety and Depression (HAD) Scale and the Cognitive Scale for Functional Bowel Disorders (FBDs), before and after 12 sessions of gut-focused HT. RESULTS: HT resulted in improvement of symptoms, quality of life and scores for anxiety and depression (all P's<.001). IBS-related cognitions also improved, with reduction in the total cognitive score (TCS; P<.001) and all component themes related to bowel function (all P<.001). Cognitions were related to symptom severity because the most abnormal cognitive scores were observed in patients with the highest symptom scores (P<.001). Furthermore, a reduction in symptom score following treatment correlated with an improvement in the cognitive score (P<.001). Regression analysis confirmed that the cognitive score had independence from the other scores and did not serve solely as a proxy for symptom improvement. CONCLUSION: This study shows that symptom improvement in IBS with HT is associated with cognitive change. It also represents an initial step in unravelling the many possible mechanisms by which treatments such as HT might bring about improvement.

Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders.

BACKGROUND & AIMS: Studies of antidepressants and psychological treatments in functional bowel disorders (FBD) are methodologically limited. The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy (CBT) against education (EDU) and desipramine (DES) against placebo (PLA) in female patients with moderate to severe FBD (irritable bowel syndrome, functional abdominal pain, painful constipation, and unspecified FBD). We also evaluated the amenability of clinically meaningful subgroups to these treatments. METHODS: This randomized, comparator-controlled, multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD. Participants received psychological (CBT vs. EDU) or antidepressant (DES vs. PLA) treatment for 12 weeks. Clinical, physiologic, and psychosocial assessments were performed before and at the end of treatment. RESULTS: The intention-to-treat analysis showed CBT as significantly more effective than EDU (P = 0.0001; responder rate, 70% CBT vs. 37% EDU; number needed to treat [NNT ], 3.1). DES did not show significant benefit over PLA in the intention-to-treat analysis (P = 0.16; responder rate, 60% DES vs. 47% PLA; NNT, 8.1) but did show a statistically significant benefit in the per-protocol analysis (P = 0.01; responder rate, 73% DES vs. 49% PLA; NNT, 5.2), especially when participants with nondetectable blood levels of DES were excluded (P = 0.002). Improvement was best gauged by satisfaction with treatment. Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms, abuse history, no depression, and diarrhea-predominant symptoms; CBT was beneficial over EDU for all subgroups except for depression. CONCLUSIONS: For female patients with moderate to severe FBD, CBT is effective and DES may be effective when taken adequately. Certain clinical subgroups are more or less amenable to these treatments.