Best Practice & Research Clinical Gastroenterology
Volume 25, Issue 1 , Pages 151-158 , February 2011

Current and future therapies for chronic constipation

  • J. Tack, MD, PhD (Professor of medicine)

      Affiliations

    • Corresponding Author InformationTARGID, Department of Pathophysiology, University of Leuven, Herestraat 49, 0&N 1, bus 701, B-3000 Leuven, Belgium. Tel.: +32 16344225; fax: +32 16344419.

References 

  1. Tack J, Müller-Lissner S. Treatment of chronic constipation: current pharmacologic approaches and future directions. Clin Gastroenterol Hepatol. 2009 May;7(5):502–508
  2. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006 Apr;130(5):1480–1491
  3. Motola G, Mazzeo F, Rinaldi B, Capuano A, Rossi S, Russo F, et al. Self-prescribed laxative use: a drug-utilization review. Adv Ther. 2002 Sep-Oct;19(5):203–208
  4. Tack J, Muller-Lissner S, Stanghellini V, Boeckxstaens G, Kamm MA, Simren M, et al. Diagnosis and treatment of chronic constipation – a European perspective. Neurogastroenterology and Motility (in press).
  5. Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol. 2005;100(4):936–971
  6. Tramonte S, Brand M, Mulrow C, Amato M, O’Keefe M, Ramirez G. The treatment of chronic constipation in adults: a systematic review. J Gen Intern Med. 1997;12(1):15–24
  7. Johanson J, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther. 2007;25(5):599–608
  8. Lederle F, Busch D, Mattox K, West MJ, Aske DM. Cost-effective treatment of constipation in the elderly: a randomized double-blind comparison of sorbitol and lactulose. Am J Med. 1990;89(5):597–601
  9. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007570
  10. Di Palma J, DeRidder P, Orlando R, Kolts B, Cleveland M. A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative. Am J Gastroenterol. 2000;95(2):446–450
  11. Di Palma JA, Cleveland MV, McGowan J, Herrera JL. An open-label study of chronic polyethylene glycol laxative use in chronic constipation. Aliment Pharmacol Ther. 2007 Mar 15;25(6):703–708
  12. Migeon-Duballet I, Chabin M, Gautier A, Mistouflet T, Bonnet M, Aubert JM, et al. Long-term efficacy and cost-effectiveness of polyethylene glycol 3350 plus electrolytes in chronic constipation: a retrospective study in a disabled population. Curr Med Res Opin. 2006;22(6):1227–1235
  13. Di Palma J, Cleveland M, McGowan J, Herrera J. A randomized, multicenter comparison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation. Am J Gastroenterol. 2007;102:1964–1971
  14. Szojda MM, Mulder CJ, Felt-Bersma RJ. Differences in taste between two polyethylene glycol preparations. J Gastrointestin Liver Dis. 2007;16(4):379–381
  15. Di Palma J, Smith J, Cleveland M. Overnight efficacy of polyethylene glycol laxative. Am J Gastroenterol. 2002;97(7):1776–1779
  16. Golzarian J, Scott H, Richards W. Hypermagnesemia-induced paralytic ileus. Dig Dis Sci. 1994;39(5):1138–1142
  17. Loening-Baucke V, Pashankar D. A randomized, prospective, comparison study of Polyethylene Glycol 3350 without electrolytes and Milk of Magnesia for children with constipation and fecal incontinence. Pediatrics. 2006;118:528–535
  18. Gondouin A, Manzoni P, Ranfaing E, Brun J, Cadranel J, Sadoun D, et al. Exogenous lipid pneumonia: a retrospective multicentre study of 44 cases in France. Eur Respir J. 1996 Jul;9(7):1463–1469
  19. Geboes K, Nijs G, Mengs U, Geboes KP, Van Damme A, de Witte P. Effects of ‘contact laxatives’ on intestinal and colonic epithelial cell proliferation. Pharmacology. 1993 Oct;47(Suppl. 1):187–195
  20. Mueller-Lissner S, Kamm MA, Wald A, Hinkel U, Koehler U, Richter E, et al. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation. Am J Gastroenterol. 2010 Apr;105(4):897–903
  21. Kienzle-Horn S, Vix JM, Schuijt C, Peil H, Jordan CC, Kamm MA. Comparison of bisacodyl and sodium picosulphate in the treatment of chronic constipation. Curr Med Res Opin. 2007;23(4):691–699
  22. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007 Jan;132(1):397–414
  23. Tack J, Camilleri M, Chang L, Chey W, Galligan JJ, Lacy BE, et al. Systematic review of cardiovascular safety profile of 5-HT4 agonists developed for GI disorders. [Submitted for publication].
  24. Tonini M, de Ponti F, di Nucci A, Crema F. Review article: cardiac adverse effects of gastrointestinal prokinetics. Aliment Pharmacol Ther. 1999;13:1585–1591
  25. Al-Judaibi B, Chande N, Gregor J. Safety and efficacy of tegaserod therapy in patients with irritable bowel syndrome or chronic constipation. Can J Clin Pharmacol. 2010 Winter;17(1):e194–e200
  26. De Maeyer JH, Lefebvre RA, Schuurkes JA. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil. 2008 Feb;20(2):99–112
  27. Bouras EP, Camilleri M, Burton DD, McKinzie S. Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans. Gut. 1999;44(5):682–686
  28. Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR. Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology. 2001;120(2):354–360
  29. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358:2344–2354
  30. Quigley EM, Vandeplassche L, Kerstens R, Ausma J. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation–a 12-week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2009;29:315–328
  31. Tack J, van Outryve M, Beyens G, Kerstens R, Vandeplassche L. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut. 2009;58:357–365
  32. Camilleri M, Beyens G, Kerstens R, Robinson P, Vandeplassche L. Safety assessment of prucalopride in elderly patients with constipation: a double-blind, placebo-controlled study. Neurogastroenterol Motil. 2009 Dec;21(12):p. 1256–e117
  33. Müller-Lissner S, Rykx A, Kerstens R, Vandeplassche L. A double-blind, placebo-controlled study of prucalopride in elderly patients with chronic constipation. Neurogastroenterol Motil. 2010 Sep;22(9):991–998e255
  34. Manini ML, Camilleri M, Goldberg M, Sweetser S, McKinzie S, Burton D, et al. Effects of velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation. Neurogastroenterol Motil. 2010 Jan;22(1):42–49e7–e8
  35. Goldberg M, Li YP, Johanson JF, Mangel AW, Kitt M, Beattie DT, 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 Nov;32(9):1102–1112
  36. Camilleri M, Vazquez-Roque MI, Burton D, Ford T, McKinzie S, Zinsmeister AR, et al. Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans. Neurogastroenterol Motil. 2007 Jan;19(1):30–38
  37. Lacy BE, Levy LC. Lubiprostone: a chloride channel activator. J Clin Gastroenterol. 2007 Apr;41(4):345–351
  38. Camilleri M, Bharucha AE, Ueno R, Burton D, Thomforde GM, Baxter K, et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G942–G947
  39. Johanson JF, Morton D, Geenen J, Ueno R. 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 Jan;103(1):170–177
  40. Barish CF, Drossman D, Johanson JF, Ueno R. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci. 2010 Apr;55(4):1090–1097
  41. Drossman DA, Chey WD, Johanson JF, Fass R, Scott C, Panas R, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome – results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009 Feb 1;29(3):329–341
  42. Bharucha AE, Waldman SA. Taking a lesson from microbial diarrheagenesis in the management of chronic constipation. Gastroenterology. 2010 Mar;138(3):813–817
  43. Andresen V, Camilleri M, Busciglio IA, Grudell A, Burton D, McKinzie S, et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. Gastroenterology. 2007 Sep;133(3):761–768
  44. Lembo AJ, Kurtz CB, Macdougall JE, Lavins BJ, Currie MG, Fitch DA, et al. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology. 2010 Mar;138(3):886–895.e1
  45. Lembo A, Schneier H, Lavins BJ, Shiff SJ, MacDougall JE, Jia XD, et al. Efficacy and safety of once daily linaclotide administered orally for 12-Weeks in patients with chronic constipation: results from 2 randomized, double-blind, placebo-controlled phase 3 trials. Gastroenterology. 2010;139:S53–S54[abstract]
  46. McNicol E, Boyce DB, Schumann R, Carr D. Efficacy and safety of mu-opioid antagonists in the treatment of opioid-induced bowel dysfunction: systematic review and meta-analysis of randomized controlled trials. Pain Med. 2008 Sep;9(6):634–659
  47. Portenoy RK, Thomas J, Moehl Boatwright ML, Tran D, Galasso FL, Stambler N, et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage. 2008 May;35(5):458–468
  48. Thomas J, Karver S, Cooney GA, Chamberlain BH, Watt CK, Slatkin NE, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008 May 29;358(22):2332–2343
  49. Mackey AC, Green L, Greene P, Avigan M. Methylnaltrexone and gastrointestinal perforation. J Pain Symptom Manage. 2010 Jul;40(1):e1–e3
  50. Webster L, Jansen JP, Peppin J, Lasko B, Irving G, Morlion B, et al. Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. Pain. 2008 Jul 15;137(2):428–440
  51. Paulson DM, Kennedy DT, Donovick RA, Carpenter RL, Cherubini M, Techner L, et al. Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction – a 21-day treatment-randomized clinical trial. J Pain. 2005 Mar;6(3):184–192
  52. Gonenne J, Camilleri M, Ferber I, Burton D, Baxter K, Keyashian K, et al. Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study. Clin Gastroenterol Hepatol. 2005;3(8):784–791
  53. Wong BS, Rao AS, Camilleri M, Manabe N, McKinzie S, Busciglio I, et al. The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health. Aliment Pharmacol Ther. 2010 Oct;32(7):884–893
  54. Coulie B, Szarka LA, Camilleri M, Burton DD, McKinzie S, Stambler N, et al. Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans. Gastroenterology. 2000 Jul;119(1):41–50
  55. Parkman HP, Rao SS, Reynolds JC, Schiller LR, Wald A, Miner PB, et al. Functional Constipation Study Investigators Neurotrophin-3 improves functional constipation. Am J Gastroenterol. 2003 Jun;98(6):1338–1347
  56. Taghavi SA, Shabani S, Mehramiri A, Eshraghian A, Kazemi SM, Moeini M, et al. Colchicine is effective for short-term treatment of slow transit constipation: a double-blind placebo-controlled clinical trial. Int J Colorectal Dis. 2010 Mar;25(3):389–394

PII: S1521-6918(11)00006-0

doi: 10.1016/j.bpg.2011.01.005

Best Practice & Research Clinical Gastroenterology
Volume 25, Issue 1 , Pages 151-158 , February 2011