Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Abstract

Irritable bowel syndrome (IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS (IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.

Keywords: Constipation; Irritable bowel syndrome; Drug therapy; Serotonergic agents; Prokinetics; 5-hydroxytryptamine type 4 agonists; Secretagogues; Prosecretory agents; Bile acid modulators

Core tip: Constipation-predominant irritable bowel syndrome (IBS-C) is one of the most common disorders seen by gastroenterologists worldwide, and is associated with a substantial burden on health care resources. Pharmacologic treatments for IBS-C have largely been unsatisfactory, mainly due to the multifaceted and poorly understood pathophysiology of this disorder. Recently approved drugs and novel investigational compounds are expected to streamline the management of IBS-C. This narrative review covers the mechanisms, clinical trial efficacies, and safety profiles of these pharmacologic agents, in order to help practicing physicians keep up with the rapidly developing field of IBS-C therapy.