Evidence-Based Reviews

5-step plan to treat constipation in psychiatric patients

Current Psychiatry. 2008 May;7(5):29-38

References

1. Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol 1999;94(12):3530-40.

2. Choung RS, Locke GR, 3rd, Schleck CD, et al. Cumulative incidence of chronic constipation: a population-based study 1988-2003. Aliment Pharmacol Ther 2007;26(11-12):1521-8.

3. Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project (HCUPnet). Available at: http://hcupnet.ahrq.gov. Accessed March 19, 2008.

4. Sonnenberg A, Koch TR. Physician visits in the United States for constipation: 1958 to 1986. Dig Dis Sci 1989;34(4):606-11.

5. Sonnenberg A, Koch TR. Epidemiology of constipation in the United States. Dis Colon Rectum 1989;32(1):1-8.

6. Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics 2005;23(5):461-76.

7. Donald IP, Smith RG, Cruikshank JG, et al. A study of constipation in the elderly living at home. Gerontology 1985;31(2):112-8.

8. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006;130(5):1480-91.

9. 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):S1-4.

10. U.S. Preventive Services Task Force. Colorectal cancer screening. Available at: http://www.ahrq.gov/clinic/3rduspstf/colorectal. Accessed March 19, 2008.

11. Chiotakakou-Faliakou E, Kamm MA, Roy AJ, et al. Biofeedback provides long-term benefit for patients with intractable, slow and normal transit constipation. Gut 1998;42(4):517-21.

12. Kawimbe BM, Papachrysostomou M, Binnie NR, et al. Outlet obstruction constipation (anismus) managed by biofeedback. Gut 1991;32(10):1175-9.

13. Richelson E. Receptor pharmacology of neuroleptics: relation to clinical effects. J Clin Psychiatry 1999;(60 suppl 10):5-14.

14. Muller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol 2005;100(1):232-42.

15. Keeling WF, Harris A, Martin BJ. Orocecal transit during mild exercise in women. J Appl Physiol 1990;68(4):1350-3.

16. Tegaserod [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2006.

17. Amitiza [package insert]. Bethesda, MD: Sucampo Pharmaceuticals; 2007.

18. Tack J, Middleton SJ, Horne MC, et al. Pilot study of the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2006;23(11):1655-65.

19. Andresen V, Camilleri M, Busciglio IA, et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. Gastroenterology 2007;133(3):761-8.

In our experience, patients usually have tried bisacodyl before seeking treatment for constipation. Although bisacodyl may be effective for some patients, others may need something stronger. Many gastroenterologists prefer prescribing osmotic or prescription laxatives.

Step 4. Osmotic laxatives generally are liquids, including magnesium hydroxide, polyethylene glycol solution, and the prescription agent lactulose. Magnesium hydroxide is inexpensive and can be taken chronically.

Algorithm

A stepwise approach to managing constipation

Step 1
Recommendation	Comments
Increase activity or daily walking	Not rigorously studied in constipated patients; exercise is associated with decreased orocecal transit time¹⁵
Increase fluid intake	Not rigorously studied in constipated patients⁸
Increase dietary fiber intake	Not rigorously studied in constipated patients⁸
↓
Step 2
Recommendation	Comments
Fiber supplements	Psyllium compounds may be superior to methylcellulose, polycarbophil, and bran¹¹
↓
Step 3
Recommendation	Comments
Over-the-counter laxative pills	Senna compounds are derived from plants
↓
Step 4
Recommendation	Comments
Over-the-counter laxative solutions	Milk of Magnesia is very inexpensive
↓
Step 5
Recommendation	Comments
Prescription laxatives	Lubiprostone causes fetal loss in animals; tegaserod is available only under a treatment investigational new drug protocol

Table 2

Commonly used laxatives: Mechanisms of action

Category	Agents
Bulk-forming	Methylcellulose (Citrucel), polycarbophil (Equalactin, Mitrolan, others), psyllium (Fiberall, Metamucil, others)
Lubricating	Glycerin (Sani-Supp), magnesium hydroxide and mineral oil (Magnolax), mineral oil (Fleet Mineral Oil, Zymenol, others)
Stool softener	Docusate sodium (Colace)
Osmotic	Magnesium hydroxide (Milk of Magnesia), polyethylene glycol (MiraLax), lactulose* (Cholac Syrup, Constulose, others), lubiprostone* (Amitiza)
Stimulant	Bisacodyl (Correctol, Dulcolax, others), castor oil (Alphamul, Emulsoil, others), senna/sennosides (Ex-Lax, Senokot, others), sodium bicarbonate and potassium bitartrate (Ceo-Two evacuant)
* Available by prescription only
Source: Reference 8

Prescription medications

Tegaserod is a partial 5-HT4 agonist and stimulator of GI motility and secretion. It also decreases visceral sensitivity.¹⁶ Tegaserod’s manufacturer voluntarily withdrew the drug from the market because it may increase risk of cardiovascular ischemic events, including angina, heart attack, and stroke. Tegaserod is available only under a treatment investigational new drug (IND) protocol that includes obtaining approval from a local institutional review board. We recommend that psychiatrists should not prescribe tegaserod but refer patients to experienced gastroenterologists or other GI specialists.

Lubiprostone is a selective chloride channel activator that works only in the gut and results in net fluid excretion and increased stool frequency. The molecule is a prostaglandin derivative and is poorly absorbed.¹⁷

Because lubiprostone has been shown to cause fetal loss in animals (at the equivalent of 2 and 6 times the recommended human dose), women of reproductive age should use contraception while taking lubiprostone and carefully consider the risks and benefits of lubiprostone use during pregnancy.

CASE CONTINUED: Finding an effective strategy

The psychiatrist prescribes lubiprostone, 24 mcg bid, but Mr. W once again complains of the expense and says the drug does not work well. He quickly returns to his intermittent use of magnesium hydroxide tablets and occasionally takes bisacodyl tablets.

To address Mr. W’s OCD, the psychiatrist adds risperidone, 0.5 mg bid, to Mr. W’s regimen. He has a modest response in OCD symptoms—30% of his day is now symptom- free— without worsening his constipation.

Probiotics and prebiotics

Emerging therapies for constipation include probiotics and prebiotics, which attempt to alter the gut flora and milieu. The primary bacterial agents are Lactobacillus species and Bifidobacterium species. At least one probiotic Bifidobacterium product—Activia—is being marketed in the United States as a fortified yogurt.

Clinical Point

Because probiotics are active cells, advise patients who try them to purchase supplements containing ‘live and active’ cultures

Because limited clinical data are available on the effect of probiotics and prebiotics on constipation, their routine use is not indicated. However, patients who prefer not to take medication may wish to try them. Because these agents are active cells, advise patients to purchase a supplement with “live and active” cultures. Supplements that are shipped, stored, or sold at room temperature likely contain very few (if any) live cultures.

Investigational medications. Renzapride is a 5HT4 receptor agonist and 5HT3 receptor antagonist that has shown promise in a pilot study¹⁸ and is in phase III trials. Linaclotide is a peptide that activates chloride and bicarbonate secretion in the gut and may reduce visceral hypersensitivity. It too has shown promise in a pilot study.¹⁹

Related resources

Rome Foundation. Functional gastrointestinal disorders. www.romecriteria.org.
Bleser S, Brunton S, Carmichael B, et al. Management of chronic constipation: recommendations from a consensus panel. J Fam Pract 2005;54(8):691-8.

Drug brand name

Amitriptyline • Elavil, Endep
Chlorpromazine • Thorazine
Clomipramine • Anafranil
Clozapine • Clozaril
Duloxetine • Cymbalta
Fluvoxamine • Luvox
Lactulose • Cholac Syrup, Constulose, others
Lubiprostone • Amitiza
Mirtazapine • Remeron
Olanzapine • Zyprexa
Risperidone • Risperdal
Thioridazine • Mellaril
Tegaserod • Zelnorm

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgment

This project was partially supported by grant number 5 T32 HS013852 from the Agency for Healthcare Research and Quality.