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.; Indications:144 patients with functional bowel disorders (Rome diagnosis: 115 irritable bowel syndrome, 13 functional constipation, 10 chronic functional abdominal pain, 6 unspecified functional bowel disorders; Physician diagnosis: 131 irritable bowel syndrome, 2 functional constipation, 5 chronic functional abdominal pain, 5 unspecified functional bowel disorders). Coexisting disease: depression (number of patients not stated).; Patients:431 patients, all women, mean age 38.6 years, were randomized. CBT group: 144 patients, mean age 37.9 years. Education group: 71 patients, mean age 36.1 years. Pertofran group: 144 patients, mean age 39.7 years. 23 dropouts due to side effects. Placebo group: 72 patients, mean age 40.1 years. 402 patients were evaluated (intention to treat population). CBT group: 135 patients. Education group: 66 patients. Pertofran group: 135 patients. Placebo group: 66 patients. 321 patients completed 8 to 12 weeks of therapy (per protocol population). CBT group: 118 patients. Education group: 50 patients. Pertofran group: 97 patients. Placebo group: 56 patients.; TypeofStudy:The efficacy of cognitive behavioral therapy (CBT), education, Pertofran or placebo was studied in women with moderate to several functional bowel disorders. Randomized, double-blind, placebo-controlled, comparative, multicenter study.; DosageDuration:Dosage: 50 mg daily as tablets for 1 week, 100 mg daily for 1 week, 150 mg daily from week 3 to week 12. Duration: 12 weeks.; ComparativeDrug:Cognitive behavioural therapy (n=144), patient education (n=71); Results:Patient compliance was 80.5% in the Pertofran group and 89.5% in the placebo group. In the intention to treat (ITT) population, CBT was superior to education (p=0.0001) in terms of the composite score but Pertofran showed a non-significant benefit over placebo (p=0.16). Differences between Pertofran and CBT and between placebo and education were not significant. Treatment benefit was explained mainly by the treatment satisfaction scale (Pertofran vs. placebo, p=0.011; CBT vs. education, p=0.0004). In the per protocol (PP) population, Pertofran was superior to placebo (p=0.03) and CBT was superior to education (p=0.001). Response rates were 73% for CBT vs. 41.3% for education (p=0.0002, number needed to treat (NNT) 3.2) and 68.5% for Pertofran vs. 49.1% for placebo (p=0.021, NNT 5.2). When 12 patients with non-detectable blood Pertofran levels were excluded from the analysis, response rates were 72.5% for Pertofran vs. 49.1% for placebo (p=0.006, NNT 4.3). This strongly suggests that Pertofran therapy is effective, provided that it is properly taken. Subgroup analysis showed that Pertofran was superior to placebo in patients with moderate symptoms, in those with a history of abuse, in those with no history of depression and in patients with diarrhea predominant symptoms. CBT was superior to education for all subgroups except patients with a history of depression.; AdverseEffects:Patients experienced mean 3.5 side effects each, including dry mouth 65, sleep disturbance 43, dizziness/light headedness 5, constipation 35, flushing/hot flashes 31, tiredness/drowsiness 27, nervous/jittery feeling 20, heartburn 18, nausea 18, headache 15, decreased appetite 14, fast irregular heartbeat 12, flu/cold 12, muscle/bone symptoms 8, rash 8.; AuthorsConclusions:DES [desipramine] is effective only for those able to stay on medication. These treatments most benefit participants with moderate more than severe symptoms and without comorbid depression. Whether other psychological treatments or other classes of antidepressants are effective needs to be determined. With growing evidence that these treatments have synergistic effects, future studies should evaluate the benefit of combined treatment with DES and CBT [cognitive behavioral therapy] for the patients not responsive to monotherapy, particularly those with more severe depression.; FreeText:Tests: Composite score, calculated from scores for treatment satisfaction, global well-being, pain rating on McGill Pain Questionnaire and quality of life on condition-specific measure (IBS-QOL); response rate; blood levels of Pertofran; patient compliance. A responder was defined as a subject who scored 28 or more on the satisfaction with treatment questionnaire.
