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 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.

Targeted therapies for diarrhea-predominant irritable bowel syndrome

“…28–33 Amitriptyline,28,29 desipramine,30,31 and imipramine32,33 have each been evaluated in two randomized controlled trials in patients with IBS. Four of these trials were small, including 51 or fewer patients,28–30,33 one included 107 patients,32 and the largest TCA trial to date included 431 patients, who were divided into two treatment groups: pharmacotherapy and psychoeducation 31.…”

Irritable Bowel Syndrome

“…Subgroup analysis [37] Systematic review NNT 4 95% CI 3 to 8 153/256 (60%) with placebo Statistically significant heterogeneity (defined as I 2 value >25%; P <0.10) between studies (I 2 = 26.9%; P = 0.21 [38] Systematic review [38] Systematic review 66/116 (57%) with SSRIs 30/111 (27%) with placebo Not significant P = 0.06 Proportion of people with global symptom relief , 12 weeks 107 people with IBS (Rome II criteria) [39] RCT 25/53 (47%) with imipramine 12/48 (25%) with placebo Not significant P = 0.59 Proportion of treatment responders , 8 weeks 54 people with IBS (Rome II criteria) [40] RCT 12/27 (44%) with citalopram 15/27 (56%) with placebo…”

“…Response defined as adequate relief of IBS symptoms for at least 3 of the past 6 weeks Not significant P = 0.24 Mean IBS symptom score , 8 weeks 54 people with IBS (Rome II criteria) [40] 107 people with IBS (Rome II criteria) [39] RCT 11.8% with imipramine…”

“…Reported as not significant P value not reported In review [38] [41] In review [38] [ 41] RCT 6/36 (17%) with placebo placebo P = 0.01 Any individual adverse effects 38/59 (64%) with imipramine 107 people with IBS (Rome II criteria) [39] RCT 19/48 (40%) with placebo -No data from the following reference on this outcome. [40] [38] ---Further information on studies [37] [38] The authors of the second review included an RCT conducted in adolescents with IBS, [38] whereas the authors of the first review restricted eligibility to trials recruiting adults.…”

“…[65] However, all but one RCT in these two reviews are >10 years old, and do not meet basic methodological quality standard criteria [39] [40] deducted for the inclusion of different types of antidepressant and assessment tool used Quality points deducted for short follow-up and heterogeneity of trials. Consistency point deducted for different results with different drugs in the same class Very low 0 0 -1 -2 4 Antispasmodic drugs versus placebo Symptom improvement 22 (at least 1828) [38] [42] [43] [44] Quality points deducted for short follow-up and methodological flaws in the RCTs included in the review Low 0 0 0 -2 4 Peppermint oil versus placebo Symptom improvement 5 (at least 482) [38] [42] [45] Quality point deducted for sparse data Moderate 0 0 0 -1 4 Peppermint oil versus placebo Quality of life 1 (90) [45] Quality points deducted for short follow-up, heterogeneity of studies, and other methodological flaws in the RCTs included in the reviews Very low 0 0 0 -3 4 Soluble fibre versus placebo Symptom improvement 5 (at least 596) [38] [42] [46] High 0 0 0 0 4 Soluble fibre versus placebo Quality of life 1 (275) [46] Quality points deducted for short follow-up and other methodological flaws in the RCTs included in the review Low 0 0 0 -2 4 Insoluble fibre versus placebo Symptom improvement 6 (at least 519) [42] [38] [46] High 0 0 0 0 4 Insoluble fibre versus placebo Quality of life 1 (275) [46] Quality points deducted for short follow-up and heterogeneity of studies.…”