Recent advances in the pharmacological management of constipation predominant irritable bowel syndrome

ABSTRACT

Introduction: Irritable bowel syndrome (IBS) is a complex functional gut disorder that typically manifests in early adult years. More than a third of IBS patients are diagnosed with predominant constipation subtype (IBS-C). This syndrome has a distressing impact on the quality of life and is challenging both for patients and physicians.

Areas covered: This review focuses on the pathophysiology of constipation in IBS and presents current management options. It also covers the latest findings that may lead to novel pharmacological options in IBS-C management. The authors intend to highlight the results of published research including abstracts, records from the clinicaltrials.gov database (second and third phases of the study) and information from original FDA documents.

Expert opinion: Current therapeutic options for IBS-C treatment are based on linaclotide, lubiprostone, plecanatide, and the reintroduced tegaserod. Drugs present on the market as well as those in pre-clinical development should increase the lower esophageal sphincter pressure, promote gastric motility, accelerate gastric emptying and improve gastro-duodenal coordination. Most significantly, they shall not induce severe side effects.

KEYWORDS:

• Irritable bowel syndrome
• constipation
• pharmacotherapy
• irritable bowel syndrome with predominant constipation

Article highlights

• IBS-C (with more than 25% of hard and fewer than 25% of loose stools according to Rome IV criteria) is diagnosed in 35.6% of patients with severe IBS.

• IBS-C is followed by complications such as fecal impaction, incontinence, hemorrhoids, anal fissure, bleeding, and bowel perforation.

• There is no single specific biochemical or structural explanation of IBS-C and clinical symptoms are always a result of an interplay between various pathophysiological factors.

• Current IBS-C management includes lifestyle improvements (short low-FODMAP interventions, relaxation, and stress avoidance techniques and improvement of the quality sleep) and non-specific treatment of symptoms.

• Currently available medications relieving IBS-C symptoms present a vast number of adverse effects.

• Considering the results of many clinical trials, novel molecules such as bile acid modulators, NHE3 inhibitors, GLP-1 analogues and serotonergic agents, seem to demonstrate the efficacy and satisfactory safety levels and can be potentially used in IBS-C treatment after completing clinical trial phase.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by a grant from the Medical University of Lodz [503/1-156-04/503-11-001 to J Fichna]