Managing functional constipation: the course doesn’t always run smooth


Chronic functional constipation is symptomatically defined and includes dyssynergic defaecation and normal and slow transit constipation, not secondary to drugs or other conditions. Dietary soluble fibre and laxatives are key treatments, with biofeedback helpful especially in dyssynergic defaecation. Newer pro-secretory and motility-stimulating agents may help those non-responsive to over-the-counter treatments. Although head-to-head and combination therapy trials are lacking, combination therapy in people not responsive to monotherapy is a reasonable approach.

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  1. 1.

    Serra J, Pohl D, Azpiroz F, et al. European society of neurogastroenterology and motility guidelines on functional constipation in adults. J Neurogastroenterol Motil. 2019;32(2):e13762.

    Google Scholar 

  2. 2.

    Forootan M, Bagheri N, Darvishi M. Chronic constipation: a review of literature. Medicine. 2018;97(20):e10631.

    Article  Google Scholar 

  3. 3.

    Pannemans J, Masuy I, Tack J. Functional constipation: individualising assessment and treatment. Drugs. 2020;80(10):947–63.

    Article  Google Scholar 

  4. 4.

    Roerig JL, Steffen KJ, Mitchell JE, et al. Laxative abuse. Drugs. 2010;70(12):1487–503.

    CAS  Article  Google Scholar 

  5. 5.

    Nelson AD, Camilleri M, Chirapongsathorn S, et al. Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis. Gut. 2017;66(9):1611–22.

    CAS  Article  Google Scholar 

  6. 6.

    Corazziari E, Badiali D, Habib FI, et al. Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation. Dig Dis Sci. 1996;41(8):1636–42.

    CAS  Article  Google Scholar 

  7. 7.

    Corazziari E, Badiali D, Bazzocchi G, et al. Long term efficacy, safety, and tolerabilitity of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut. 2000;46(4):522–6.

    CAS  Article  Google Scholar 

  8. 8.

    Dipalma JA, Cleveland MV, McGowan J, et al. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol. 2007;102(7):1436–41.

    CAS  Article  Google Scholar 

  9. 9.

    DiPalma JA, DeRidder PH, Orlando RC, et al. A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative. Am J Gastroenterol. 2000;95(2):446–50.

    CAS  Article  Google Scholar 

  10. 10.

    Attar A, Lémann M, Ferguson A, et al. Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation. Gut. 1999;44(2):226–30.

    CAS  Article  Google Scholar 

  11. 11.

    Cinca R, Chera D, Gruss HJ, et al. Randomised clinical trial: macrogol/PEG 3350 + electrolytes versus prucalopride in the treatment of chronic constipation—a comparison in a controlled environment. Aliment Pharmacol Ther. 2013;37(9):876–86.

    CAS  Article  Google Scholar 

  12. 12.

    Wesselius-De Casparis A, Braadbaart S, Bergh-Bohlken GE, et al. Treatment of chronic constipation with lactulose syrup: results of a double-blind study. Gut. 1968;9(1):84–6.

    CAS  Article  Google Scholar 

  13. 13.

    Herve S, Savoye G, Behbahani A, et al. Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation. Neurogastroenterol Motil. 2004;16(4):397–402.

    CAS  Article  Google Scholar 

  14. 14.

    Manabe N, Cremonini F, Camilleri M, et al. Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers. Aliment Pharmacol Ther. 2009;30(9):930–6.

    CAS  Article  Google Scholar 

  15. 15.

    Schryver AM, Samsom M, Smout AI. Effects of a meal and bisacodyl on colonic motility in healthy volunteers and patients with slow-transit constipation. Dig Dis Sci. 2003;48(7):1206–12.

    Article  Google Scholar 

  16. 16.

    Mueller-Lissner S, Kamm MA, Wald A, et al. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation. Am J Gastroenterol. 2010;105(4):897–903.

    CAS  Article  Google Scholar 

  17. 17.

    Kamm MA, Mueller-Lissner S, Wald A, et al. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol. 2011;9(7):577–83.

    CAS  Article  Google Scholar 

  18. 18.

    Barish CF, Drossman D, Johanson JF, et al. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci. 2010;55(4):1090–7.

    CAS  Article  Google Scholar 

  19. 19.

    Johanson JF, Morton D, Geenen J, et al. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation. Am J Gastroenterol. 2008;103(1):170–7.

    CAS  Article  Google Scholar 

  20. 20.

    Lembo AJ, Johanson JF, Parkman HP, et al. Long-term safety and effectiveness of lubiprostone, a chloride channel (ClC-2) activator, in patients with chronic idiopathic constipation. Dig Dis Sci. 2011;56(9):2639–45.

    CAS  Article  Google Scholar 

  21. 21.

    Tien XY, Brasitus TA, Kaetzel MA, et al. Activation of the cystic fibrosis transmembrane conductance regulator by cGMP in the human colonic cancer cell line, Caco-2. J Biol Chem. 1994;269(1):51–4.

    CAS  Article  Google Scholar 

  22. 22.

    Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011;365(6):527–36.

    CAS  Article  Google Scholar 

  23. 23.

    Schoenfeld P, Lacy BE, Chey WD, et al. Low-dose linaclotide (72 μg) for chronic idiopathic constipation: a 12-week, randomized, double-blind, placebo-controlled trial. Am J Gastroenterol. 2018;113(1):105–14.

    CAS  Article  Google Scholar 

  24. 24.

    Lacy BE, Schey R, Shiff SJ, et al. Linaclotide in chronic idiopathic constipation patients with moderate to severe abdominal bloating: a randomized controlled trial. PLoS ONE. 2015;10(7):e0134349.

    Article  Google Scholar 

  25. 25.

    Miner PB, Koltun WD, Wiener GJ, et al. A randomized phase III clinical trial of plecanatide, a uroguanylin analog, in patients with chronic idiopathic constipation. Am J Gastroenterol. 2017;112(4):613–21.

    CAS  Article  Google Scholar 

  26. 26.

    Shin A, Camilleri M, Kolar G, et al. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther. 2014;39(3):239–53.

    CAS  Article  Google Scholar 

  27. 27.

    Camilleri M, Kerstens R, Rykx A, et al. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358(22):2344–54.

    CAS  Article  Google Scholar 

  28. 28.

    Tack J, Stanghellini V, Dubois D, et al. Effect of prucalopride on symptoms of chronic constipation. Neurogastroenterol Motil. 2014;26(1):21–7.

    CAS  Article  Google Scholar 

  29. 29.

    Piessevaux H, Corazziari E, Rey E, et al. A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of long-term treatment with prucalopride. Neurogastroenterol Motil. 2015;27(6):805–15.

    CAS  Article  Google Scholar 

  30. 30.

    Goldberg M, Li YP, Johanson JF, et al. Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation: a 4-week, randomized, double-blind, placebo-controlled, dose-response study. Aliment Pharmacol Ther. 2010;32(9):1102–12.

    CAS  Article  Google Scholar 

  31. 31.

    Palme M, Milner PG, Ellis DJ, et al. A novel gastrointestinal prokinetic, ATI-7505, increased spontaneous bowel movements (SBMs) in a phase ii, randomized, placebo-controlled study of patients with chronic idiopathic constipation (CIC) [abstract no. 905]. Gastroenterology. 2010;138:S128–9.

    Article  Google Scholar 

  32. 32.

    Chey WD, Camilleri M, Chang L, et al. A randomized placebo-controlled phase IIb trial of a3309, a bile acid transporter inhibitor, for chronic idiopathic constipation. Am J Gastroenterol. 2011;106(10):1803–12.

    CAS  Article  Google Scholar 

  33. 33.

    Oduyebo I, Camilleri M, Nelson AD, et al. Effects of NGM282, an FGF19 variant, on colonic transit and bowel function in functional constipation: a randomized phase 2 trial. Am J Gastroenterol. 2018;113(5):725–34.

    CAS  Article  Google Scholar 

  34. 34.

    Woodward S, Norton C, Chiarelli P. Biofeedback for treatment of chronic idiopathic constipation in adults. Cochrane Database Syst Rev. 2014;2014(3):CD008486.

    Google Scholar 

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Correspondence to Connie Kang.

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C. Fenton and C. Kang are contracted/salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Fenton, C., Kang, C. Managing functional constipation: the course doesn’t always run smooth. Drugs Ther Perspect (2021).

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