Barbara H. Bradshaw

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.

Regional Brain Activation in Response to Rectal Distension in Patients with Irritable Bowel Syndrome and the Effect of a History of Abuse

Previous studies have demonstrated alterations in brain response to rectal distension in patients with irritable bowel syndrome (IBS) compared to controls. Our aim was to compare regional brain activity in response to rectal balloon distension in patients with IBS and healthy controls. We studied six patients with IBS and six healthy controls. Positron emission tomography scans were obtained during rectal balloon distensions. Statistical parametric mapping and region of interest analysis were performed to identify and compare differences in regional cerebral blood flow (CBF) for each distension pressure within and between the groups of interest. In post-hoc analyses, patients with a history of sexual or physical abuse were compared to patients without abuse. In response to rectal distension, controls exhibit a greater increase in anterior cingulate cortex (ACC) activity compared to the IBS group (Z = 3.2, P = 0.001). Thalamic activity was higher in the IBS patients relative to the control group (Z = 3.3, P < 0.001). Increased ACC activity was observed in IBS patients with no history of abuse (Z = 5.2, P < 0.001) similar to controls, whereas no such increased activity was noticed in the abused group. In conclusion, this study replicates previous findings showing alterations in brain response to rectal distension in patients with IBS. The observations on the effect of abuse suggest a possible modulating role of abuse history on this brain response.

Fundoplication improves disordered esophageal motility

Patients with gastroesophageal reflux disease (GERD) and disordered esophageal motility are at risk for postoperative dysphagia, and are often treated with partial (270-degree) fundoplication as a strategy to minimize postoperative swallowing difficulties. Complete (360-degree) fundoplication, however, may provide more effective and durable reflux protection over time. Recently we reported that postfundoplication dysphagia is uncommon, regardless of preoperative manometric status and type of fundoplication. To determine whether esophageal function improves after fundoplication, we measured postoperative motility in patients in whom disordered esophageal motility had been documented before fundoplication. Forty-eight of 262 patients who underwent laparoscopic fundoplication between 1995 and 2000 satisfied preoperative manometric criteria for disordered esophageal motility (distal esophageal peristaltic amplitude ≤30 mm Hg and/or peristaltic frequency ≤80%). Of these, 19 had preoperative manometric assessment at our facility and consented to repeat study. Fifteen (79%) of these patients had a complete fun-doplication and four (21%) had a partial fundoplication. Each patient underwent repeat four-channel esophageal manometry 29.5 ± 18.4 months (mean ± SD) after fundoplication. Distal esophageal peristaltic amplitude and peristaltic frequency were compared to preoperative data by paired t test. After fun-doplication, mean peristaltic amplitude in the distal esophagus increased by 47% (56.8 ± 30.9 mm Hg to 83.5 ± 36.5 mm Hg; P < 0.001) and peristaltic frequency improved by 33% (66.4 ± 28.7% to 87.6 ± 16.3%; P< 0.01). Normal esophageal motor function was present in 14 patients (74%) after fundoplication, whereas in five patients the esophageal motor function remained abnormal (2 improved, 1 worsened, and 2 remained unchanged). Three patients with preoperative peristaltic frequencies of 0%, 10%, and 20% improved to 84%, 88%, and 50%, respectively, after fundoplication. In most GERD patients with esophageal dysmotility, fundoplication improves the amplitude and frequency of esophageal peristalsis, suggesting refluxate has an etiologic role in motor dysfunction. These data, along with prior data showing that postoperative dysphagia is not common, imply that surgeons should apply complete fun-doplication liberally in patients with disordered preoperative esophageal motility.