Effects of desipramine on irritable bowel syndrome compared with atropine and placebo

Greenbaum, David S.; Mayle, James E.; Vanegeren, Lawrence E.; Jerome, John; Mayor, Joan; Greenbaum, Ruth B.; Matson, Robert W.; Stein, Gary E.; Dean, Howard A.; Halvorsen, Nancy A.; Rosen, Lionel W.

doi:10.1007/bf01297051

Cited by 169 publications

(85 citation statements)

References 36 publications

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“…Their mechanism in IBS is not completely understood, but has been postulated to relate to an ability to modulate central and peripheral pain perception [110,111] , improve underlying psychiatric conditions, and possibly improve gut motility through modification of neurotransmitter activity [112,113] . Unfortunately, randomized-controlled trials to date have largely been hindered by poor study design and methodological flaws, making it difficult to judge the therapeutic value of these agents [114][115][116] . Most studies provide little evidence that antidepressants are superior to placebo in improving specific IBS-related symptoms, but some do suggest that overall global well-being may be improved.…”

Section: Antidepressantsmentioning

confidence: 99%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

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Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated to affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

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Section: Antidepressantsmentioning

confidence: 99%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

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“…Moreover, trials should include baseline assessment of symptoms, account for patient disposition (discontinuations, withdrawals, etc), provide sample size calculation and enroll an adequate number of patients, with the primary outcome being improvement of global IBS symptoms based on patient assessment and/or use of a validated scale to assess IBS symptoms [3] . To date, 10 randomized, controlled trials and two crossover studies have evaluated the effectiveness of TCAs in the treatment of IBS [10][11][12][13][14][15][16][17][18] . The largest and best study to date on TCAs was done by Drossman et al [19] , investigating the role of desipramine in patients with functional disorders.…”

Section: Discussionmentioning

confidence: 99%

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

Abdul‐Baki¹,

Hajj²,

El-Zahabi³

et al. 2009

WJG

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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.

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“…A metaanalysis of randomized controlled trials concluded that the tricyclic antidepressants were superior to placebo in IBS with an number needed to treat (NNT) of 3 [51], although the individual trial results and the quality of the trials has been variable [52][53][54][55][56]. Greenbaum et al for example in a study of desipramine 150 mg daily separated diarrhoea from constipation-predominant IBS, and reported that diarrhoea, abdominal pain and depression but not constipation improved with active drug therapy, compared with atropine or placebo [52]. Ritchie & Truelove also reported that abdominal pain and diarrhoea but not constipation or bloating improved with a combination of nortryptiline 30 mg and fluphenazine 1.5 mg [53].…”

Section: Antidepressants and Anxiolyticsmentioning

confidence: 99%

Evaluation of drug treatment in irritable bowel syndrome

Talley

2003

Brit J Clinical Pharma

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The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents relieve the symptoms of IBS; constipation probably improves. Anticholinergic and antispasmodic agents are of questionable benefit in IBS despite positive meta-analyses of poor quality trials. A meta-analysis concluded that the tricyclic antidepressants were superior to placebo in IBS, although the individual trial results were variable. Selective serotonin reuptake inhibitors are of uncertain benefit. Laxatives are used for constipation but probably poorly control the IBS symptom complex. Loperamide is superior to placebo in improvement of diarrhoea but not abdominal pain in IBS. Tegaserod is a well-tolerated aminoguanidine indole derivative of serotonin that is a partial 5HT 4 -receptor agonist with prokinetic properties; a therapeutic gain over placebo of 5% to 15% has been observed in constipation-predominant IBS in females. Alosetron is a 5HT 3 -receptor antagonist that is efficacious in females with diarrhoea-predominant IBS, with a 12% to 17% therapeutic gain; the risk of ischaemic colitis is 1 in 350, with very severe constipation occurring in about 1 in 1000. Optimizing study design remains a challenge in IBS. New visceral analgesic and motility modifying agents, as well as anti-inflammatory agents are in trials, and hopefully additional efficacious therapeutic options for patients with IBS will soon emerge.

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Effects of desipramine on irritable bowel syndrome compared with atropine and placebo

Cited by 169 publications

References 36 publications

Updates on treatment of irritable bowel syndrome

Updates on treatment of irritable bowel syndrome

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

Evaluation of drug treatment in irritable bowel syndrome

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