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From American Journal of Health-System Pharmacy

Rationale for Using Serotonergic Agents to Treat Irritable Bowel Syndrome

Danial E. Baker

Abstract and Introduction
Abstract
Purpose: The role of serotonin in gastrointestinal (GI)-tract functioning, the pharmacologic rationale for using serotonergic agents in the treatment of irritable bowel syndrome (IBS), and clinical experience with novel serotonergic agents are described.
Summary: IBS is a common multisymptom disorder that is associated with a high socioeconomic burden. The goal of treatment is to provide rapid and sustained global relief of the multiple symptoms of IBS with a single, effective, well-tolerated agent. Traditional treatment options target single symptoms, and many patients are dissatisfied with the level of relief achieved and adverse effects. Research has revealed that serotonin is involved in three major actions in the gut: (1) mediating intestinal motility, (2) mediating intestinal secretion in the GI tract, and (3) modulating perception in the bowels. Serotonin is also a vital link in the brain-gut axis. Alterations in key elements of serotonin signaling have been demonstrated in patients with IBS. Tegaserod, a selective serotonin type 4 (5-HT4)-receptor partial agonist, is indicated for use in women with IBS whose primary bowel symptom is constipation. Alosetron, a 5-HT3-receptor antagonist, is indicated for use in women with severe diarrhea-predominant IBS in whom traditional therapies have failed. The clinical usefulness of several other serotonergic agents for IBS is being investigated.
Conclusion: The use of serotonergic agents in patients with IBS is based on the critical role that serotonin plays in the maintenance of normal gut function and brain-gut communication. Pharmacologic therapies targeting specific serotonin receptors represent an important step in the management of IBS.

Introduction
Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by abdominal pain or discomfort and altered bowel habits.[1] Traditional treatment options for patients with IBS target single symptoms, are often ineffective, and can cause bothersome adverse effects in some patients.[2] During the past two decades, important research strides have enhanced our understanding of the underlying pathophysiology of IBS. The understanding of the critical role that serotonin plays in maintaining normal GI-tract function (e.g., motility, secretion, and sensation) and of the vital link between serotonin and the enteric nervous system (ENS), the autonomic nervous system (ANS), and the central nervous system (CNS)[3] has resulted in the development of several serotonergic agents as potential therapies for IBS.[1,4]

Two serotonergic agents currently have FDA-approved labeling for use in the treatment of IBS: tegaserod maleate, a selective serotonin type 4 (5-HT4)-receptor partial agonist indicated for women with IBS whose primary bowel symptom is constipation (IBS-C),[5] and alosetron hydrochloride, a 5-HT type 3 (5-HT3)-receptor antagonist indicated for women with severe IBS with diarrhea (IBS-D) in whom traditional therapies have failed to provide adequate relief.[6] Other serotonergic agents are currently in development.

This article discusses the role of serotonin in GI-tract functioning, the pharmacologic rationale for using serotonergic agents in the treatment of IBS, and clinical experience with novel serotonergic agents.

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Danial E. Baker, Pharm.D., FASCP, FASHP, is Associate Dean, Clinical Programs; Director, Drug Information Center; and Professor of Pharmacotherapy, Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, WA

Am J Health-Syst Pharm. 2005; 62 (7): 700-711. �2005 American Society of Health-System Pharmacists

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