Constipation - Emerging treatments

Tenapanor

Tenapanor is a first-in-class inhibitor of the gastrointestinal sodium-proton exchanger NHE3, which reduces dietary sodium absorption leaving more fluid in the gut to loosen stool and alleviate constipation. One phase 3 trial of tenapanor for irritable bowel syndrome with constipation reported significantly improved symptoms compared with placebo.[104]

Sacral nerve stimulation (SNS)

SNS may ease symptoms of slow-transit constipation or evacuation disorder by stimulating afferent and efferent nerves, contributing to better awareness.[18] One systematic review (based mostly on retrospective studies) reported a pooled treatment success rate 57% to 87% for patients with chronic constipation who received permanent implants.[105] Three subsequent randomised controlled trials on sacral nerve stimulation for slow-transit constipation found that SNS did not improve the frequency of complete bowel movements.[106][107][108] Despite this, the European Society of Neurogastroenterology and Motility guidelines suggest that SNS may be a reasonable option to consider before more invasive surgery.[18]

5-HT(4) agonists

Velusetrag and naronapride are highly selective 5-HT(4) agonists that have demonstrated the ability to improve all components of regional gastrointestinal transit, including gastric emptying, small bowel transit, and colonic transit times.[109][110] Both of these agents have also shown to improve a number of spontaneous bowel movements in chronic idiopathic constipation in phase 2 clinical trials; however, they are not commercially available yet.[111][112] In one systematic review of drugs for chronic constipation, velusetrag was associated with the most diarrhoea or drop-out due to adverse events.[64]

Elobixibat

Elobixibat is an ileal bile acid transport blocker that allows more bile into the colon causing laxation. In one phase 3 trial, elobixibat was more effective than placebo, but 40% of patients in the 52-week open-label trial experienced mild gastrointestinal adverse effects.[113]

Lactitol

Lactitol is an osmotic laxative available as a powder for oral solution. The Food and Drug Administration (FDA) has approved lactitol for treatment of chronic constipation in adults based on one phase 3 trial, but more high-quality studies are needed.[18][114]

Habit training

Habit training (pelvic floor retraining), which involves dietary advice, basic anatomy education, and simple pelvic floor exercises led by non-physicians, has been developed for patients with resistant chronic constipation.[115] One retrospective study of 347 mostly (82%) female patients showed an improvement in symptoms and quality of life score.[116] The 2020 European Society of Neurogastroenterology and Motility guideline recommends habit training is effective when expertise is available, but highlights that the approach is not standardised or evidence-based.[18] More large-scale RCTs are needed to recommend this method to patients with refractory constipation.