Carolyn B. Morris

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.

International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit.

Background Although clinicians generally make treatment decisions in irritable bowel syndrome (IBS) related to the type of symptoms, other factors such as the perceived severity and the risks patients are willing to tolerate for effective treatment are also important to consider. These factors are not fully understood. Objective To describe among patients with IBS their symptoms and severity, quality of life and health status, medications taken, and the risk that they would take to continue medications for optimal relief. Methods Adult patients diagnosed with IBS who accessed the websites of the International Foundation for Functional GI Disorders or the University of North Carolina Center for Functional GI Disorders filled out questionnaires to address the study aims. Results The 1966 respondents (83% female, 91% white, 78% US/Canada) reported impaired health status: restricting on average 73 days of activity in a year, having poor health-related quality of life particularly with dietary restrictions, mood disturbance, and interference with daily activity, and 35% reported their symptoms as severe defined primarily as pain, bowel difficulties, bloating, and eating/dietary restrictions). These symptoms were reported in some combination by over 90%, and 35.1% endorsed all 4 items. To receive a treatment that would make them symptom free, patients would give up 25% of their remaining life (average 15 y) and 14% would risk a 1/1000 chance of death. Most of the medications being taken were for pain relief and 18% were taking narcotics. Complementary and alternative treatments were used by 37%. Conclusions Patients accessing IBS informational websites report moderate-to-severe impairments in health status, and would take considerable risk to obtain symptom benefit. There is an unmet need to find effective treatments for patients with IBS and regulatory agencies might consider raising risk-benefit ratios when approving new medications for IBS.

What patients know about irritable bowel syndrome (IBS) and what they would like to know. National Survey on Patient Educational Needs in IBS and development and validation of the Patient Educational Needs Questionnaire (PEQ).

Patient education improves clinical outcomes in patients with chronic illness, but little is known about the education needs of patients with IBS.OBJECTIVES: The objective of this study was to identify: (1) patients perceptions about IBS; (2) the content areas where patients feel insufficiently informed, i.e., “knowledge gaps” about diagnosis, treatment options, etiology, triggers, prognosis, and role of stress; and (3) whether there are differences related to items 1 and 2 among clinically significant subgroups.METHODS: The IBS-Patient Education Questionnaire (IBS-PEQ) was developed using patient focus groups and cognitive item reduction of items. The IBS-PEQ was administered to a national sample of IBS patients via mail and online.ANALYSIS: Frequencies of item endorsements were obtained. Clinically relevant groups, (a) health care seekers or nonhealth care seekers and (b) users or nonusers of the Web, were identified and grouped as MD/Web, MD/non-Web, and non-MD/Web.RESULTS: 1,242 patients completed the survey (371 via mail and 871 online), mean age was 39.3 ± 12.5 yr, educational attainment 15 ± 2.6 yr, 85% female, IBS duration 6.9 ± 4.2 yr, 79% have seen an MD for IBS in the last 6 months, and 92.6% have used the Web for health information. The most prevalent IBS misconceptions included (% of subjects agreeing with the statement): IBS is caused by lack of digestive enzymes (52%), is a form of colitis (42.8%), will worsen with age (47.9%), and can develop into colitis (43%) or malnutrition (37.7%) or cancer (21.4%). IBS patients were interested in learning about (% of subjects choosing an item): (1) foods to avoid (63.3%), (2) causes of IBS (62%), (3) coping strategies (59.4%), (4) medications (55.2%), (5) will they have to live with IBS for life (51.6%), and (6) research studies (48.6%). Patients using the Web were better informed about IBS.CONCLUSION: (1) Many patients hold misconceptions about IBS being caused by dietary habits, developing into cancer, colitis, causing malnutrition, or worsening with age; (2) patients most often seek information about dietary changes; and (3) educational needs may be different for persons using the internet for medical information.

A Very Low-Carbohydrate Diet Improves Symptoms and Quality of Life in Diarrhea-Predominant Irritable Bowel Syndrome

BACKGROUND & AIMS Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This study prospectively evaluated a VLCD in IBS-D. METHODS Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 g carbohydrates/d). A responder was defined as having adequate relief of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life also were measured. RESULTS Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting adequate relief for all 4 VLCD weeks. Stool frequency decreased (2.6 +/- 0.8/d to 1.4 +/- 0.6/d; P < .001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score, 5.3 +/- 0.7 to 3.8 +/- 1.2; P < .001). Pain scores and quality-of-life measures significantly improved. Outcomes were independent of weight loss. CONCLUSIONS A VLCD provides adequate relief, and improves abdominal pain, stool habits, and quality of life in IBS-D.

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.

The development and validation of a new coeliac disease quality of life survey (CD-QOL).

Aliment Pharmacol Ther 31, 666–675

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%; κ 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.

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:Detectible 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.

Development of Abdominal Pain and IBS Following Gynecological Surgery: A Prospective, Controlled Study

BACKGROUND & AIMS Irritable bowel syndrome (IBS) develops after bacterial enteritis that causes injury to the bowel mucosa. Its unclear whether abdominal pain or IBS results from gynecological surgery that could injure abdominopelvic nerves. The aim of this prospective, controlled study was to assess the incidence of pain or IBS in women undergoing elective gynecological surgery compared to non-surgical controls and to identify factors associated with their development. METHODS One hundred thirty-two women without GI symptoms undergoing elective gynecological surgery for non-painful conditions were compared with 123 non-surgery controls without GI symptoms. Socio-demographic, psychosocial, and surgery-related variables were potential predictor variables of pain at 3 and/or 12 months. RESULTS Three surgical patients (2.7%), but no controls, developed IBS at 12 months. Significantly more surgical patients had abdominal pain at 3 or 12 months (15.3% vs 3.6%, P=.003). No socio-demographic or surgery-related variables predicted pain development, but it was predicted by psychosocial factors including anticipation of difficult recovery from surgery (P=.01), perception of severity/constancy of illness (P=.04), and reduced sense of coherence (P=.01). CONCLUSIONS Among women undergoing gynecological for non-pain indications the development of IBS was not significantly greater than controls. However, abdominal pain did develop in 17% of women in the surgical group, suggesting that surgery facilitated its development. Notably, only psychosocial variables predicted pain development, implying that pain development associated with central registration and amplification of the afferent signal (via cognitive and emotional input) must be considered along with the peripheral injury itself. These findings contribute to understanding the pathophysiology of functional GI pain.

Psychosocial Factors Are More Important Than Disease Activity in Determining Gastrointestinal Symptoms and Health Status in Adults at a Celiac Disease Referral Center

BackgroundThe relative effects of clinical and psychosocial variables on outcome in celiac disease (CD) has not previously been reported. In adult patients with (CD), we studied the relationships among demographics, psychosocial factors, and disease activity with health-related quality of life (HRQOL), health care utilization, and symptoms.MethodsAmong 101 adults newly referred to a tertiary care center with biopsy-proven CD we assessed: (a) demographic factors and diet status; (b) disease measures (Marsh score, tissue transglutaminase antibody (tTG) level, weight change and additional blood studies); and (c) Psychosocial status (psychological distress, life stress, abuse history, and coping). Multivariate analyses were performed to predict HRQOL, daily function, self-reported health, number of physician visits, and GI symptoms (pain and diarrhea).ResultsImpaired HRQOL and daily function was associated with psychological distress and poorer coping. Self-report of poorer health was associated with poorer coping, longer symptom duration, lower education, and greater weight loss. More physician visits were associated with poorer coping, abnormal tTG levels, and milder Marsh classification. Greater pain scores were seen in those with higher psychological distress and greater weight loss. Finally, diarrhea was associated with greater psychological distress and poorer coping.ConclusionsIn patients presenting to a CD referral center, psychosocial factors more strongly affect health status and GI symptoms than disease measures.