US Pharm. 2010;35(12):74-85.

Constipation accounts for approximately 2.7 million physician office visits, is responsible for an annual cost of about $8 billion per patient, and occurs in 12% to 19% of the U.S. population.1,2 Constipation is more prevalent in children, the elderly, women, and Blacks, as well as in people of lower socioeconomic standing and those who live in rural or northern areas of the U.S.3


Chronic constipation (CC) may have a primary or a secondary cause. Primary (i.e., no underlying cause) constipation is classified into three main types: normal-transit (or functional) constipation (NTC), slow-transit constipation (STC), and dyssynergic defecation (DD).4 In NTC, stool passes through the colon at a normal pace; patients commonly experience formation of hard stools or difficulty evacuating.5 STC, which predominantly occurs in young women, is usually characterized by delayed emptying from the proximal colon to the distal colon and rectum.4 DD is commonly caused by failure of the pelvic floor or external anal sphincter to relax when defecation is attempted.6

Potential secondary causes of CC are metabolic abnormalities, neurologic disorders, psychological disorders, lifestyle factors, and medications (TABLE 1).7


Classification of constipation by the Rome III Criteria8 requires a patient to have experienced at least two of the following symptoms over the past 3 months: fewer than three bowel movements per week, straining, lumpy/hard stools, sensation of anorectal obstruction, sensation of incomplete defecation, or manual maneuvering required to defecate. Irritable bowel syndrome (IBS) must be ruled out before this diagnostic tool is used.


See TABLE 2 for a summary of management guidelines.

Lifestyle Modifications

Hydration: Hydration is often recommended because it is believed that hard, small stools will soften and overall stool output will increase; however, studies have yielded variable results. In a study of 15 healthy volunteers, increased consumption of isotonic or hypotonic solutions did not increase stool output.9 However, in a study of 80 healthy males, low fluid intake decreased stool weight (P = .048).10 Decreased fluid intake was among the factors associated with constipation in a study of nursing home patients.11 A randomized, controlled trial (RCT) of 11 healthy volunteers ingesting 15 g of wheat bran twice daily (± 600 mL fluid supplementation) found no difference in transit time, stool weight, or frequency.12 In an RCT of 170 NTC patients, consumption of a high-fiber diet (25 g/day) plus fluid supplementation (1.5-2 L/day) resulted in an increased stool frequency (P <.0001) and decreased laxative use (P <.001).13 Patients at risk for dehydration (i.e., elderly, fluid consumption <600 mL/day) may be more prone to NTC. Targeted efforts to provide proper hydration become paramount in the management of patients with NTC if there is evidence of dehydration or low fluid intake.

Physical Activity: Colonic motor function is affected by physical activity. Eighty percent of low-amplitude propagated contractions occur during the day, with a significant increase upon waking in the morning and after meals.14 Several studies showed that moderate physical activity improved mild constipation, especially in the elderly. A cross-sectional study of more than 39,000 women found a 24% lower incidence of constipation in those who engaged in low-to-moderate activity compared with sedentary women.15 In a cross-sectional survey of the bowel habits of 200 elderly subjects living at home, poor mobility and depression had the highest association with constipation.16 A study examining risk factors related to constipation in elderly patients suggested an increased risk of constipation in those who walked less than 0.5 km daily (relative risk [RR] 1.7), walked with help (RR 3.4), or were chairbound (RR 6.9) or bedridden (RR 15.9), comparatively.17 However, in a study of eight subjects aged 19 to 64 years with CC who engaged in regular exercise (5 hours/week), increased physical activity did not improve constipation indices.18 Regular physical activity has a notable effect on constipation in elderly patients, but a comprehensive approach to managing symptoms should be taken.

Pharmacologic Interventions

TABLE 3 gives recommended maximum doses of specific products.

Bulk-Forming Laxatives: Bulk-forming laxatives are natural or synthetic polysaccharides or cellulose derivatives that work by absorbing water and increasing fecal mass, thereby increasing the frequency and softening the consistency of stool.4 Bulk-forming laxatives include bran, psyllium, methylcellulose, calcium polycarbophil, and wheat dextrin. Psyllium undergoes bacterial fermentation in the colon, which produces gas and bloating, and generally is poorly tolerated. Powder formulations of psyllium often feel gritty when mixed with liquids. Wheat dextrin is a tasteless, colorless, soluble fiber that can be dissolved in most foods or beverages and does not cause bloating.19

Increased fiber intake generally is not beneficial in patients with STC or DD. Several small studies examining the effects of fiber (14-20 g/day) on constipation failed to show a difference in STC or DD patients.20-23 A meta-analysis found that bran consumption increased stool weight and decreased transit time, but had little effect on constipation.14 Fiber consumption is only somewhat effective in constipated patients with known fiber deficiency.14 Psyllium is the most studied bulk-forming laxative; limited data exist for calcium polycarbophil, methylcellulose, and wheat dextrin.24 Two RCTs showed that psyllium use resulted in greater stool frequency and consistency.25,26 The American College of Gastroenterology (ACG)-CC Task Force limits its recommendation to the use of psyllium for increasing stool frequency in patients with CC.27

Osmotic Laxatives: Osmotic laxatives include saline agents, poorly absorbed sugars, and polyethylene glycol (PEG). These agents work by creating an osmotic gradient within the intestinal lumen, thereby retaining water in the intestinal lumen. Saline laxatives, which work within 0.5 to 3 hours, are salts of magnesium hydroxide or poorly absorbed ions. The main complications of these treatments are electrolyte imbalances, especially in renal failure. Lactulose and PEG are approved for the treatment of constipation and are the most-studied agents of this class. Currently, the ACG-CC Task Force supports the use of lactulose and PEG for the treatment of CC.27 In a parallel study of 24 patients, lactulose 40 g/day increased stool frequency (P <.05) and improved stool consistency (P = .01).28 In a second parallel study of 47 patients, the use of lactulose 20 g/day increased stool frequency (P = .05).29 Lactulose 10 to 20 g/day has a higher success rate of relieving constipation symptoms (P <.05).30

In several placebo-controlled RCTs, PEG doses up to 35 g per day resulted in increased stool frequency (P <.05; specific trial) and improved stool consistency.31-35 In a crossover study comparing PEG with placebo or lactulose in 57 patients, nonhard stools were more frequent in lactulose- or PEG-treated patients (P <.05).36 In a parallel study of PEG (26 g/day) versus lactulose (20 g/day) in 99 subjects, stool frequency was higher with PEG, as were straining and overall effectiveness (P <.05).37

Stool Softeners: Stool softeners are surface-acting agents that allow water to more easily enter the stool. A crossover study of 15 subjects that compared docusate calcium 240 mg twice daily versus placebo found no difference in stool frequency.38 When docusate sodium (stool softener) 100 mg twice daily was compared with psyllium 5.1 g twice daily in 170 patients, docusate had few side effects but was less effective than psyllium in improving stool frequency (P <.05).39 Two studies showed that stool softeners were effective at improving stool frequency and subjective global assessment of effectiveness.40,41 There is little evidence to support the use of stool softeners, and these products are generally considered to be less effective than psyllium for the management of CC.27

Stimulant Laxatives: Stimulant laxatives alter electrolyte transport, increase water uptake into intestinal mucosa, and increase motor activity. Stimulant laxatives have caused abdominal discomfort, electrolyte imbalance, and hepatotoxicity.42 Senna-containing compounds have been associated with melanosis coli, a condition in which damage leads to apoptosis of cells in the large intestine. Traditionally, melanosis coli has been linked to an increased risk of colorectal cancers.42,43 However, there is recent evidence that chronic use of stimulant laxatives does not increase the risk of colorectal tumors.14 In a crossover study of 164 patients that compared stimulant laxatives with lactulose 20 g/day, the percentage of patients passing normal stools by day 7 was greater with lactulose (58% vs. 42%, P <.05).44 Stimulant laxatives may be more effective if used in combination with a bulk-forming laxative.45 Stimulant laxatives should not be considered first-line agents for CC owing to limited data supporting their use and their poor safety profile. The ACG-CC Task Force found insufficient data to make a determination about the effectiveness of these laxatives.27

Lubricants, Enemas, and Suppositories: Mineral oil, a lubricant, softens fecal content by coating it and preventing colonic absorption of fecal water. Tap-water and normal-saline enemas create bulk through an osmotic volume effect. Vegetable-oil enemas act as a lubricant, while soap enemas create an irritant effect. Soap enemas are generally not recommended because of the increased risk of proctitis or colitis. Suppositories stimulate peristaltic movement of the colon, which is facilitated by the local irritation of the rectum. Bisacodyl-containing suppositories are often used when the distal colon requires cleaning. Glycerin suppositories are useful for initiating the defecation reflex in children and for promoting rectal emptying in adults.24 In children, mineral oil was shown to be superior to senna-based laxatives for stool frequency and stool consistency, and inferior to osmotic laxatives.46,47 Given the lack of RCTs in adults, the ACG-CC Task Force concluded that these data were inadequate to allow a recommendation.27

Tegaserod: Tegaserod is a 5-HT4 receptor agonist in the enteric nervous system that causes stimulation of peristaltic reflex, colonic motility, colonic lumen secretion, and decreased visceral hypersensitivity.48 It was approved in 2004 for constipation-predominant IBS in women aged under 55 years and for primary constipation.48 A meta-analysis of safety data from 29 clinical trials involving more than 18,000 patients found a higher risk of cardiovascular events; this led to suspension of the drug's marketing and sales in 2007 and to the restricted use of tegaserod under a treatment investigational new drug (IND).49 In 2008, the manufacturer (Novartis) voluntarily made tegaserod available as an emergency IND, which means that physicians may prescribe it for cases that are life-threatening or require hospitalization. Information about the emergency IND process may be obtained from the FDA's Division for Drug Information by e-mailing

Lubiprostone: Lubiprostone is a selective chloride channel activator. It acts in the apical membrane of the gastrointestinal epithelium to enhance chloride-rich intestinal fluid secretion by intraluminal fluid collection in the gut.50 The agent was approved in 2006 for the treatment of primary constipation in adults. In a 3-week, placebo-controlled, phase III RCT of 129 adults, lubiprostone (24, 48, or 72 mcg/day) increased spontaneous bowel movement frequency (P <.05).51 In a large, multicenter, double-blind, placebo-controlled RCT of 242 adults, lubiprostone 24 mcg twice daily caused a greater number of spontaneous bowel movements at week 4 (P <.001).52 The most common adverse events were nausea (29%), diarrhea, headache, and abdominal distention.51,52

Alternative Therapy

Biofeedback: Biofeedback involves measuring a subject's quantifiable bodily functions (i.e., blood pressure, heart rate, temperature, sweat gland activity, and muscle tension) and conveying the information to the patient in real time to increase the patient's conscious control of his or her unconscious physiologic activities. Biofeedback can correct inappropriate contraction of the pelvic-floor muscles and the external anal sphincter during defecation in patients with DD.4 In RCTs, biofeedback was found to be more effective than continuous PEG for DD.53


The goal of managing CC is to improve the patient's quality of life while reducing the complications of CC. The pharmacist should review the patient's medications and herbal supplements to rule out secondary causes of CC. The pharmacist also plays an integral role in choosing appropriate therapies for primary constipation and monitoring the efficacy and toxicity of these agents. Lifestyle modifications including increased fiber intake, hydration, and increased physical activity should be recommended when appropriate, and patient education should be implemented.


1. Martin BC, Barghout V, Cerulli A. Direct medical costs of constipation in the United States. Manag Care Interface. 2006;19:43-49.
2. Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99:750-759.
3. Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics. 2005;23:461-476.
4. Cash BD, Chang L, Sabesin SM, Vitat P. Update on the management of adults with chronic idiopathic constipation. J Fam Pract. 2007;56(suppl 6):S13-S19.
5. Ashraf W, Park F, Lof J, Quigley EM. An examination of the reliability of reported stool frequency in the diagnosis of idiopathic constipation. Am J Gastroenterol. 1996;91:26-32.
6. Rao SS. Constipation: evaluation and treatment. Gastroenterol Clin North Am. 2003;32:659-683.
7. Koch A, Voderholzer WA, Klauser AG, Müller-Lissner S. Symptoms in chronic constipation. Dis Colon Rectum. 1997;40:902-906.
8. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130:1480-1491.
9. Young RJ, Beerman LE, Vanderhoof JA. Increasing oral fluids in chronic constipation in children. Gastroenterol Nurs. 1998;21:156-161.
10. Klauser AG, Beck A, Schindlbeck NE, Müller-Lissner SA. Low fluid intake lowers stool output in healthy male volunteers. Z Gastroenterol. 1990;28:606-609.
11. Robson KM, Kiely DK, Lembo T. Development of constipation in nursing home residents. Dis Colon Rectum. 2000;43:940-943.
12. Ziegenhagen DJ, Tewinkel G, Kruis W, Herrmann F. Adding more fluid to wheat bran has no significant effects on intestinal function in healthy subjects. J Clin Gastroenterol. 1991;13:525-530.
13. Anti M, Pignataro G, Armuzzi A, et al. Water supplementation enhances the effect of high-fiber diet on stool frequency and laxative consumption in adult patients with functional constipation. Hepatogastroenterology. 1998;45:727-732.
14. Müller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol. 2005;100:232-242.
15. Sullivan SN, Wong C, Heidenheim P. Does running cause gastrointestinal symptoms? A survey of 93 randomly selected runners compared with controls. N Z Med J. 1994;107:328-331.
16. Donald IP, Smith RG, Cruikshank JG, et al. A study of constipation in the elderly living at home. Gerontology. 1985;31:112-118.
17. Kinnunen O. Study of constipation in a geriatric hospital, day hospital, old people's home and at home. Aging (Milano). 1991;3:161-170.
18. Meshkinpour H, Selod S, Movahedi H, et al. Effects of regular exercise in management of chronic idiopathic constipation. Dig Dis Sci. 1998;43:2379-2383.
19. Benefiber (wheat dextrin) product information. Parsippany, NJ: Novartis Consumer Health, Inc; 2009.
20. Preston DM, Lennard-Jones JE. Severe chronic constipation of young women: 'idiopathic slow transit constipation'. Gut. 1986;27:41-48.
21. Anderson AS. Dietary factors in the aetiology and treatment of constipation during pregnancy. Br J Obstet Gynaecol. 1986;93:245-249.
22. Klauser AG, Peyerl C, Schindlbeck NE, Müller-Lissner SA. Nutrition and physical activity in chronic constipation. Eur J Gastroenterol Hepatol. 1992;4:227-233.
23. Towers AL, Burgio KL, Locher JL, et al. Constipation in the elderly: influence of dietary, psychological, and physiological factors. J Am Geriatr Soc. 1994;42:701-706.
24. Brandt LJ, Prather CM, Quigley EM, et al. Systematic review on the management of chronic constipation in North America. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
25. Fenn GC, Wilkinson PD, Lee CE, Akbar FA. A general practice study of the efficacy of Regulan in functional constipation. Br J Clin Pract. 1986;40:192-197.
26. Ashraf W, Park F, Lof J, Quigley EM. Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation. Aliment Pharmacol Ther. 1995;9:639-647.
27. American College of Gastroenterology Chronic Constipation Task Force. An evidence-based approach to the management of chronic constipation in North America. Am J Gastroenterol. 2005;100(suppl 1):S1-S4.
28. Bass P, Dennis S. The laxative effects of lactulose in normal and constipated subjects. J Clin Gastroenterol. 1981;3:23-28.
29. Sanders JF. Lactulose syrup assessed in a double-blind study of elderly constipated patients. J Am Geriatr Soc. 1978;26:236-239.
30. Wesselius-De Casparis A, Braadbaarrt S, Bergh-Bohlken GE, Mimica M. Treatment of chronic constipation with lactulose syrup: results of a double-blind study. Gut. 1968;9:84-86.
31. Chen H, Li X, Ge Z. Comparative study on two colonic bowel preparations for patients with chronic constipation. Scand J Gastroenterol. 2009;44:375-379.
32. Di Palma JA, Cleveland MB, McGowan J, Herrera JL. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol. 2007;102:1436-1441.
33. Di Palma JA, Cleveland MB, McGowan J, Herrera JL. An open-label study of chronic polyethylene glycol laxative use in chronic constipation. Aliment Pharmacol Ther. 2007;25:703-708.
34. Chaussade S, Minic M. Comparison of efficacy and safety of two doses of two different polyethylene glycol-based laxatives in the treatment of constipation. Aliment Pharmacol Ther. 2003;17:165-172.
35. Corazziari E, Badiali D, Bazzocchi G, et al. Long term efficacy, safety, and tolerability of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut. 2000;46:522-526.
36. Freedman MD, Schwartz HJ, Roby R, Fleisher S. Tolerance and efficacy of polyethylene glycol 3350/electrolyte solution versus lactulose in relieving opiate induced constipation: a double-blinded placebo-controlled trial. J Clin Pharmacol. 1997;37:904-907.
37. 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;44:226-230.
38. Castle SC, Cantrell M, Israel DS, Samuelson MJ. Constipation prevention: empiric use of stool softeners questioned. Geriatrics. 1991;46:84-86.
39. McRorie JW, Daggy BP, Morel JG, et al. Psyllium is superior to docusate sodium for treatment of chronic constipation. Aliment Pharmacol Ther. 1998;12:491-497.
40. Hyland CM, Foran JD. Dioctyl sodium sulphosuccinate as a laxative in the elderly. Practitioner. 1968;200:698-699.
41. Fain AM, Susat R, Herring M, Dorton K. Treatment of constipation in geriatric and chronically ill patients: a comparison. South Med J. 1978;71:677-680.
42. Xing JH, Soffer E. Adverse effects of laxatives. Dis Colon Rectum. 2001;44:1201-1209.
43. Connolly P, Hughes IW, Ryan G. Comparison of “Duphalac” and “irritant” laxatives during and after treatment of chronic constipation: a preliminary study. Curr Med Res Opin. 1974-1975;2:620-625.
44. Passmore AP, Davies KW, Flanagan PG, et al. A comparison of Agiolax and lactulose in elderly patients with chronic constipation. Pharmacology. 1993;47(suppl 1):249-252.
45. Kinnunen O, Winblad I, Koistinen P, Salokannel J. Safety and efficacy of a bulk laxative containing senna versus lactulose in the treatment of chronic constipation in geriatric patients. Pharmacology. 1993;47(suppl 1):253-255.
46. Tolia V, Lin CH, Elitsur Y. A prospective randomized study with mineral oil and oral lavage solution for treatment of faecal impaction in children. Aliment Pharmacol Ther. 1993;7:523-529.
47. Sondheimer JM, Gervaise EP. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. J Pediatr Gastroenterol Nurs. 1982;1:223-226.
48. Zelnorm (tegaserod maleate) product information. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2005.
49. Food and Drug Administration. Public Health Advisory: tegaserod maleate (marketed Zelnorm).
PostmarketDrugSafetyInformatio nforPatientsandProviders/ DrugSafetyInformationforHeathc areProfessionals/ PublicHealthAdvisories/ ucm051284.htm. Accessed October 29, 2010.
50. Amitiza (lubiprostone) product information. Bethesda, MD: Sucampo Pharmaceuticals Inc; April 2008.
51. Johanson JF, Gargano MA, Holland PC, et al. Phase III efficacy and safety of RU-0211, a novel chloride channel activator, for the treatment of constipation [abstract]. Gastroenterology. 2003;124:A104.
52. Johanson JF, Gargano MA, Holland PC, et al. Phase III study of lubiprostone, a chloride channel-2 (CIC-2) activator for the treatment of constipation: safety and primary efficacy [abstract]. Am J Gastroenterol. 2005;100(suppl 9):S328-S329.
53. Chiarioni G, Whitehead WE, Pezza V, et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology. 2006;130:657-664.

To comment on this article, contact