Doxepin is More Effective than Nortriptyline and Placebo for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Triple-Blind Placebo-Controlled Trial

Background: The current treatment of IBS is often unsatisfactory and frustrating. Several controlled trials have demonstrated benefits of tricyclic antidepressants for irritable bowel syndrome, especially when pain is a prominent symptom but the efficacy of antidepressants in irritable bowel syndrome is controversial. The aim of this study was to compare the effect of doxepin and nortriptyline on diarrhea-predominant irritable bowel syndrome.Methods: Seventy-five patients with IBS according to Rome III criteria were treated for two months. The patients were randomly assigned to one of three groups treated with doxepin, nortriptyline or placebo. Subjects were assessed clinically one month and two months after treatment. The symptoms and adverse effects of the drugs were recorded in the questionnaire. The total score was considered as the number of the symptoms for each patient, which ranged between zero and six.Results: Improvements in abdominal pain and bloating in the doxepin group were significantly higher than the nortriptyline or the placebo groups (P=0.001 and P=0.012, respectively). However, improvement in diarrhea in patients on nortriptyline was significantly higher than the other groups (P=0.018). The average improvement of symptoms in the patients after two months of treatment in doxepin, nortriptyline and placebo groups, respectively were 2.56, 2 and 0.6 (P<0.05).Conclusion: Both doxepin and nortriptyline are effective for the treatment of diarrhea-predominant irritable bowel syndrome in a period of two months but doxepin seems to be more efficacious than nortriptyline in this regard. However, larger comparative trials are suggested