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

Abstract

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 component-specific 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.

Figure 1

Study design.

Figure 2

Rate of global symptom relief (A) per-protocol and (B) per intent-to-treat analysis (^aP < 0.05).

Figure 3

Percent mean SF-36 before and after treatment (^aP < 0.05).