A randomized controlled trial of imipramine in patients with irritable bowel syndrome

AIM： To study the efficacy of low-dose imipramine in relieving symptoms associated with the irritable bowel syndrome （IBS）. METHODS： A randomized, double-blind trial of 25 mg imipramine vs matched placebo for 12 wk was performed. Doubling the dose was allowed once at week 2 in case of an unsatisfactory early response. Primary efficacy variables were subjective global symptom relief and quality of life （QoL） using SF-36 at week 12. RESULTS： One hundred and seven patients were enrolled by advertisement or referral by general practitioners and 56 （31 imipramine： 25 placebo） completed the 16-wk study. Baseline characteristics were comparable. A high overall dropout rate was noted in the imipramine and placebo arms （47.5% vs 47.9%, P 〉 0.05）, a mean of 25.0 and 37.4 d from enrollment, respectively （P 〈 0.05）. At the end of 12 wk, there was a significant difference in global symptom relief with imipramine over placebo （per-protocol： 80.6% vs 48.0%, P = 0.01） and a trend on intent-to-treat （ITT） analysis （42.4% vs 25.0%, P = 0.06）. This improvement was evident early and persisted to week 16 （P = 0.024 and 0.053 by per-protocol and ITT analyses, respectively）. Mean cumulative and componentspecific SF-36 scores improved in the imipramine group only （per-protocol, P 〈 0.01）. Drug-related adverse events leading to patient dropout were more common in the imipramine group （25.4% vs 12.5%, P 〉 0.05）. CONCLUSION： Imipramine may be effective in the treatment of IBS patients and is associated with improved QoL. Careful patient selection, initiation of a low dose with gradual escalation and monitoring for side effects may result in an improved therapeutic response.