Christine B. Dalton

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.

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.

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.

Atypical Antipsychotic Quetiapine in the Management of Severe Refractory Functional Gastrointestinal Disorders

Management of severe refractory functional gastrointestinal disorders (FGIDs) is difficult. Quetiapine, an atypical antipsychotic, may benefit patients by mitigating associated anxiety and sleep disturbances, augmenting the effect of antidepressants, and providing an independent analgesic effect. Outpatient records from a university-based FGID clinic were reviewed, and 21 patients with refractory symptoms who received quetiapine were identified and interviewed. Outcomes included global relief of symptoms, treatment efficacy questionnaire, and change in gastrointestinal (GI) and psychological symptoms. Eleven of 21 patients continued therapy at the time of interview. Six of 11 demonstrated global relief of symptoms, and 9 were satisfied with treatment. The remaining 10 of 21 discontinued therapy because of somnolence and lack of GI benefits. Quetiapine in low doses appeared beneficial in more than half of the adults with severe FGIDs who stayed on treatment. This response in otherwise refractory patients suggests quetiapine might augment the effectiveness of antidepressants in severe FGIDs.

Is clinical response to tricyclic antidepressants in functional bowel disorders related to dosage

Background: Desipramine (DES) is effective in treating moderate to severe Functional Bowel Disorder (FBD) over Placebo(PLA) as shown in the per protocol analysis of a Randomized, Controlled trial (Drossman at al, Gastroenterology 2003). Clinical experience suggests that benefit from antidepressants in FBD can be achieved at doses lower than those used to treat major depression. However, it is not known if monitoring the DES plasma levels in respect to dose adjustments or predicting clinical outcome in patients with FBD is clinically useful. Aim: To determine whether clinical response to DES is related to DES blood levels or number of pills taken. We report the correlation between DES dose and plasma level, DES dose and chnical outcome and DES plasma level and clinical outcome. Methods: As part of a study of antidepressant and psychological treatments in 431 patients with FBD at UNC or U of Ioronto, we studied those participants in the per protocol analysis taking DES (N = 95, dose 50-150 rag/day) or pill placebo (PLA) (N=55 1-3 pilLs/day). A composite outcome score (Satisfaction with treatment and McGill pain Questionnaires, global Well-being, and IBS-QOL) of clinical response was correlated with: 1)DES plasma levels at week 6 of a 12 week study, and 2) number of pills taken over sequential weekly periods (weeks 0-12,212,4-12,6-12,8-12,10-12) for participants taking DES and PLA. In addition, a correlation was obtained comparing number of DES pills taken with DES plasma levels. Results: 1) There is a correlation between DES blood levels at week 6 and DES dose during weeks 5&6 (R= 0.28, p<0.05); 2) There is no association between DES dose for any sequence of weeks or for DES blood levels at week 6 and the composite score at week 12; 3) These findings held for the DES group after those with non detectable blood levels were excluded; 4) There was no correlation between number of placebo pills taken with the composite score or blood levels (non detectable). Conclusions: For patients with moderate to severe FBD treated with DES, there is a modest correlation between DES dose and plasma level. However, the clinical response is not determined by the DES dose or plasma level. This supports the cresting wisdom that patients with FBD may respond even to low doses (e.g., 50 mg or less) of DES. Monitoring the DES plasma levels in patients with FBD appears not clinically useful unless toxicity is suspected Supported by N1H Grant R01DK49334.