Consensus Report: Clinical Trial Guidelines for Pharmacological Treatment of Irritable Bowel Syndrome

E. Corazziari, P. Bytzer, M. Delvaux, G. Holtmann, J. R. Malagelada, J. Morris**, S. Muller-Lissner, R. C. Spiller, J. Tack, P. J. Whorwell

Disclosures

Aliment Pharmacol Ther. 2003;18(6) 

In This Article

Therapeutic Options

An effective physician-patient relationship, patient education, reassurance and judicious dietary instructions are prerequisites for any treatment of irritable bowel syndrome. Many treatments, both pharmacological and non-pharmacological, have been proposed for irritable bowel syndrome. However, the efficacy of current therapeutic options is not satisfactory for the following reasons: (i) benefit has been poorly documented for the majority of proposed treatments; (ii) when documented, the benefit is often limited to specific irritable bowel syndrome symptoms, such as diarrhoea, constipation or pain; and (iii) benefit occurs in a limited number of patients, usually not exceeding 10-20%.

Non-pharmacological options include changes in the fibre content of the diet, both increases and decreases, biofeedback and psychological treatment.

Increasing fibre in the diet and the use of bulking agents have been shown to improve bowel movements in functional constipation without any beneficial effect on abdominal symptoms;[40] their efficacy in irritable bowel syndrome patients has not been clearly established.[41] In addition, a high-fibre diet does not apply in diarrhoea-predominant irritable bowel syndrome and is poorly tolerated by the majority of irritable bowel syndrome patients. In fact, dietary fibre supplements may worsen abdominal discomfort,[42] and some patients benefit from exclusion diets which reduce the fibre content substantially.[43]

Psychological treatment involving psychotherapy, hypnotherapy and relaxation techniques, including biofeedback procedures aimed at managing stress, have been reported to improve some of the symptoms of irritable bowel syndrome.[44,45,46] However, they have no effect on the symptoms of constipation and constant abdominal pain. The favourable effects of psychological treatment are more evident in patients with overt psychiatric disorders and those with stress-exacerbated symptoms.[47] In addition, psychological treatments have mainly been studied in selected tertiary care patients who have not responded to standard management. Two systematic reviews of the literature have concluded that the efficacy of psychological treatments has not been established[41,48] and, in any case, they should best be regarded as treatment options in the case of pharmacotherapy failure or as an adjunct to pharmacotherapy.

Pharmacological options aim to control irritable bowel syndrome symptoms, bowel alterations and abdominal pain with drugs mainly targeted to the gastrointestinal tract or the central nervous system.

The majority of the available drugs have been tested and are used in the management of individual symptoms, and not to control the whole range of symptoms inherent in the complex irritable bowel syndrome. Loperamide has been shown to be effective in the control of functional diarrhoea, and osmotic and contact laxatives and polyethylene solution in the control of functional constipation. These agents, however, have no effect on, or may even aggravate, other symptoms, such as pain and bloating.[49,50] In addition, their use is indicated only as a symptomatic, on-demand treatment in selected patients, as their effect may be unpredictable or even undesirable in the majority of irritable bowel syndrome patients who present with an alternating bowel pattern.

The smooth muscle relaxants, cimetropium bromide, pinaverium bromide, octilonium bromide, trimebutine and mebeverine, have been shown to be more effective than placebo in three meta-analyses.[41,51,52] On average, the global symptom improvement with myorelaxants exceeded that of placebo by 22%. However, the benefit was due essentially to their effect on abdominal pain and abdominal distension (18% and 14% over placebo, respectively) with no effect on bowel alterations.[52]

Besides being of limited value, the therapeutic benefit of myorelaxants was demonstrated in clinical trials that were hampered by methodological problems. The trials were performed in non-homogeneous groups of patients who presented with different types of functional bowel alterations and were not selected on the basis of standardized irritable bowel syndrome symptom-based criteria.

Psychotropic drugs, mainly low-dosage tricyclic antidepressants, have been used in non-constipated irritable bowel syndrome patients with abdominal pain as the chief complaint. A meta-analysis based on a few uncontrolled trials indicated that they were useful in about one-third of patients.[53] However, their efficacy has not been assessed in randomized, double-blind, placebo-controlled trials.*

*After submission of this article, a randomised, double-blind, placebo-controlled trial has been published showing that the tricyclic antidepressant desipramine may be effective in clinical subgroups of patients with functional bowel disorders (Drossman DA, Toner BB, Whitehead WE, et al. Gastroenterology 2003; 125: 19-31.

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