Constipation - Emerging treatments | BMJ Best Practice US

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.[106]

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.[107] Three subsequent randomized controlled trials on sacral nerve stimulation for slow-transit constipation found that SNS did not improve the frequency of complete bowel movements.[108][109][110] 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.[111][112] 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.[113][114] In one systematic review of drugs for chronic constipation, velusetrag was associated with the most diarrhea or drop-out due to adverse events.[67]

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.[115]

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][116]

Habit training

Habit training (pelvic floor retraining), which involves dietary advice, basic anatomy education, and simple pelvic floor exercises led by nonphysicians, has been developed for patients with resistant chronic constipation.[117] One retrospective study of 347 mostly (82%) female patients showed an improvement in symptoms and quality of life score.[118] 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 standardized or evidence-based.[18] More large-scale RCTs are needed to recommend this method to patients with refractory constipation.