Current and emerging treatments for irritable bowel syndrome with constipation and chronic idiopathic constipation: focus on prosecretory agents

Abstract

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are two common functional gastrointestinal disorders that impair quality of life and pose a significant economic burden to the health care system. Current therapeutic options include lifestyle modifications, over-the-counter (OTC) agents, antispasmodics, serotonin agonists, and lubiprostone and linaclotide, two prosecretory prescription drugs approved for the treatment of IBS-C and CIC. This review discusses the efficacy and safety of current treatments and emerging therapies for the treatment of IBS-C and CIC, with a focus on the prosecretory agents. A search of the PubMed database (1966-November 2014) was performed to identify relevant articles; clinical trials on emerging agents were also identified by searching the ClinicalTrials.gov registry. OTC laxatives may relieve constipation but do not treat abdominal pain and discomfort. Antispasmodics may provide short-term relief in patients with IBS-C, but their utility is limited by anticholinergic adverse effects. Tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors have shown benefit in providing global symptom relief and in improving abdominal discomfort, but further research is needed. Phase III clinical trials have demonstrated the efficacy of lubiprostone and linaclotide relative to placebo for the short-term treatment of IBS-C and CIC, with improvements reported in stool frequency, perceived constipation severity, and abdominal pain and discomfort. Relatively small response rates, higher costs, and adverse effects associated with lubiprostone and linaclotide will likely render these agents suitable as second-line therapies in the treatment of IBS-C and CIC. Emerging potential treatment options include prucalopride, plecanatide, elobixibat, and tenapanor. Several of these emerging therapies have novel mechanisms of action and may show promise in patients with IBS-C and CIC who have not responded to other therapies.

Keywords: chronic idiopathic constipation; constipation; irritable bowel syndrome; irritable bowel syndrome with constipation; treatments.