A Randomized Double-Blind Placebo-Controlled Trial of Imipramine in Patients with Irritable Bowel Syndrome

Purpose: To study the efficacy of low-dose Imipramine in relieving symptoms associated with the irritable bowel syndrome (IBS). Methods: Randomized double-blind trial of 25 mg imipramine vs. matched placebo for 12 weeks. Doubling the dose was allowed once at week 2 if necessary. Primary efficacy variables were subjective global symptom relief at week 12 and general quality of life questionnaire (SF-36) compared to baseline. Results: 107 patients were enrolled by advertisement or upon referral by general practitioners and 56 (31 imipramine: 25 placebo) completed the 16-week study. Baseline characteristics were comparable. A high overall drop-out rate was noted in the imipramine and placebo arms (47.5% vs. 47.9%, p= NS) a mean of 25.0 and 37.4 days from enrollment respectively (p= 0.026). Adherence to treatment was less common amongst self-referred patients. At the end of 12 weeks, there was a significant difference in global symptom relief with imipramine over placebo (per-protocol: 80.6% vs. 48.0%; p= 0.01, and intent-to-treat: 42.4% vs. 25.0%, p= 0.06). This improvement was evident early and persisted by week 16 (p= 0.02 and 0.053 for PP and ITT analyses respectively). Mean cumulative and component-specific SF36 scores improved significantly only in the imipramine group (p < 0.01). Drug-related adverse events leading to patient drop-out were more common in the imipramine group (25.4% vs. 12.5%; p= NS). Conclusions: This study suggests that imipramine is effective in the treatment of IBS patients and is associated with improved quality of life. Careful patient selection, gradual dose escalation and monitoring are likely to result in improved therapeutic response.