Treatments for Constipation From Selective Serotonin 5-HT4 Receptor Agonists to Acupuncture

There is no one size fits all approach for relieving chronic constipation because the medical and environmental conditions associated with the condition are vast and complex.

Achieving optimal blood sugar levels can relieve mild cases of constipation in some patients with diabetes, but for secondary constipation, which is drug-induced, the patient’s medications should be adjusted if necessary.


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Other considerations should be made as well. In diabetes patients, anorectal disorders are prevalent and the patient should be screened for pelvic floor muscle dysfunction, according to Marc S. Piper, MD, and Richard J. Saad, MD, writing in the December 2017 issue of Current Treatment Options in Gastroenterology. They recommend colonic transit testing for patients who fail to respond to laxative therapies.

Kovesdy et al write that the fundamental key to properly managing the condition is to identify and address the etiologic, pathophysiologic, and symptomatic factors associated with the condition in each patient.

Non-pharmacological modifications, such as changes in diet, exercise, and the use of fiber supplements, are more effective for patients with primary constipation. But for secondary constipation, which is drug-induced, pharmacological interventions will most likely be required.

Pharmacological treatment options include laxative compounds such as bulk-forming and osmotic laxatives, stimulants, stool softeners, and lubricants. There are also newer agents of different mechanisms of action, such as chloride channel activators, guanylate cyclase C receptor agonists, selective serotonin 5-HT4 receptor agonists, and ileal bile acid transporter inhibitors.

The American College of Gastroenterology Evidence-Based Monograph and a practice guideline from the American Gastroenterological Association recommend bulk-forming and osmotic agents (such as psyllium and polyethylene glycol) supplemented by stimulant laxatives before using one of the newer agents.

“When there is failure of these agents to either individually, or as combination therapy, [relieve constipation], a variety of pro-secretory agents can be considered,” according to Marc S. Piper, MD, and Richard J. Saad, MD, writing in the December 2017 issue of Current Treatment Options in Gastroenterology.9 “All of these agents require a prescription. This includes the peripheral acting guanylate cyclase-C agonists, linaclotide, and plecanatide. Both agents have been shown to stimulate intestinal fluid secretion and transit.”

Lubiprostone, a peripheral-acting derivative from prostaglandin E1 that activates CIC-2 chloride channels stimulating intraluminal fluid secretion, was studied in a group of 76 patients with diabetes. In study results published in 2017 in the American Journal of Gastroenterology, researchers reported that after 4 weeks of treatment, patients who received lubiprostone had a 20.3 ± 7.3 h difference in colonic transit time than placebo.(9)

Observational studies have shown that nontraditional treatments, such as cannabidiol, can be effective in relieving constipation. And, small studies have shown that acupuncture can offer relief from constipation.

Guangju Zhou, PhD, of the Affiliated Hospital of North Sichuan Medical College, Sichuan, China, is currently conducting a review(1) of existing studies that show acupuncture is effective in relieving constipation. Small studies have shown that acupuncture with electrical stimulation of nerves in the stomach several times each week is also effective in treating chronic constipation.

An Overlooked Area of Study

Despite the increased presence of colonic conditions in diabetes patients, few clinical trials have been conducted, and there is limited evidence-based treatment for diabetes-related constipation, Piper et al wrote.

“Despite this increased risk for these oftentimes chronic colonic conditions, there are few clinical trials in diabetics. In most cases, treatment is extrapolated from studies in the general population or those with functional bowel disorders. It is important for the clinician to be aware of these associated conditions with diabetes mellitus as prevention, early detection, and treatment will improve outcomes. This also underscores the need for more clinical trials, especially treatment trials in the setting of constipation and diarrhea in diabetics,” the study authors wrote.

References

1. Sumida K, Molnar MZ, Potukuchi PK, et al. Constipation and incident CKD. J Am Soc Nephrol. 2017;28(4):1248-1258. doi:10.1681/ASN.2016060656

2. Kubota Y, Iso H, Tamakoshi A; JACC Study Group. Bowel movement frequency, laxative use, and mortality from coronary heart disease and stroke among japanese men and women: the Japan Collaborative Cohort (JACC) Study. J Epidemiol. 2016;26(5):242-248. doi:10.2188/jea.JE20150123 

3. Honkura K, Tomata Y, Sugiyama K, et al. Defecation frequency and cardiovascular disease mortality in Japan: the Ohsaki cohort study. Atherosclerosis. 2016;246:251-256. doi:10.1016/j.atherosclerosis.2016.01.007

4. Sumida K, Molnar MZ, Potukuchi PK. Constipation and risk of death and cardiovascular events. Atherosclerosis. 2019;281:114-120. doi:10.1016/j.atherosclerosis.2018.12.021

5. Salmoirago-Blotcher E, Crawford S, Jackson E, Ockene J, Ockene I. Constipation and risk of cardiovascular disease among postmenopausal women. Am J Med. 2011;124:714-723. doi:10.1016/j.amjmed.2011.03.026 

6. Honkura K, Tomata Y, Sugiyama K., et al. Defecation frequency and cardiovascular disease mortality in Japan: the Ohsaki cohort study. Atherosclerosis. 2016;246:251-256. doi:10.1016/j.atherosclerosis.2016.01.007

7. Sumida K, Yamagata K, Kovesdy C. Constipation in CKD. Kidney International Reports. 2020;5(2):121-134. doi:10.1016/j.ekir.2019.11.002

8. Piper M, Saad R. Diabetes mellitus and the colon. Curr Treat Options Gastroenterol.. 2017.15(4):460-474. doi:10.1007/s11938-017-0151-1 

9. Christie J, Shroff S, Shahnavaz N, et al. A randomized, double-blind, placebo-controlled trial to examine the effectiveness of lubiprostone on constipation symptoms and colon transit time in diabetic patients. Am J Gastroenterol. 2017;112(2):356-364. doi:10.1038/ajg.2016.531

10. Cui S, Yang Q, Xie S, Liu Q, Zhou G. Acupuncture for chronic constipation in patients with diabetes mellitus: a protocol for systematic review. Medicine. 2021;100(9):e24886. doi:10.1097/MD.0000000000024886