# Presentation: 728308

## Chronic Constipation:  An Unresolved Problem forMany Patients

**Charlene Prather, MD**
**Division of Gastroenterology and Hepatology **
**Saint Louis University School of Medicine**

## Presentation Objectives

**Definition of chronic constipation**
**Epidemiology and resource utilization**
**Review of available therapies and limitations**
**Unmet medical need **

**C**

## Definition: Causes of Chronic Constipation

**Secondary**
**Drug induced **
**Metabolic factors**
**Comorbid conditions**
**Primary**
**Impaired colonic transit/motility **
**Altered neuroenteric function and reflexes**
**Failure of muscular apparatus**
**Ineffective defecation (functional outlet obstruction)**
**Pelvic dyssynergia and anismus**
**Normal transit constipation**

**C**

## Constipation Is a Constellation of Symptoms

**Most commonly reported symptoms**
**Hard, lumpy stools**
**Increased straining**
**Infrequent bowel movements**
**Sensation of incomplete evacuation**
**Bloating/fullness**
**Chronic constipation**
**More persistent than intermittent or episodic**
**Several months duration**

**C**

## Constipation Is More Than JustInfrequent Passage of Stool

**Sandler RS, et al. *****Dig Dis Sci.***** 1987;32:841-845.**

**n = 1128**

**Constipation Is More Than Just****Infrequent Passage of Stool**

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**Constipation symptoms reported most often**

## Reduced Stool Frequency Is Not the Most Commonly Reported Symptom in Constipation

**EPOC = Epidemiology of constipation; BM = Bowel movement.**
**1. Stewart WF, et al. *****Am J Gastroenterol*****. 1999;94:3530-3540.**
**2. Paré P, et al. *****Am J Gastroenterol*****. 2001;96:3130-3137.**

**Stewart (EPOC) 1999****1**

**Paré**** 2001****2**

**n = 1476**

**n = 1149**

**Constipation symptoms reported most often**

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## Rome II Defines Functional Constipation Based on Multiple Symptoms

**Rome II diagnostic criteria for functional constipation**
**At least 12 wk, which need not be consecutive, over the past 12 months of 2 or more of **
**Straining***
**Lumpy or hard stools***
**Sensation of incomplete evacuation***
**Sensation of anorectal obstruction/blockage***
**Manual maneuvers to facilitate defecation***
**< 3 defecations/wk**
**Loose stools not present**
**Insufficient criteria for IBS**

*** ****> 1/4 of defecations.**
**Drossman DA, et al. In: *****Rome II: The Functional Gastrointestinal Disorders*****. 2000:382-391.**

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## Prevalence in the General Population

**1. Stewart WF, et al. *****Am J Gastroenterol*****. 1999;94:3530-3540.**
**2. ****Drossman DA, et al. *****Dig Dis Sci.***** 1993;38:1569-1580.**
**3. Harris Interactive Study, Wave 2. Data on file. ****4. Paré P, et al. *****Am J Gastroenterol.***** 2001;96:3130-3137.**

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| Population | n | Criteria | Prevalence, n (%) |
| --- | --- | --- | --- |
| US1 | 10,018 | Rome I |    461 (4.6) |
| US2 | 5430 | Rome I |    195 (3.6) |
| US3 | 15,183 | Rome II | 2429 (16) |
| Canada4 | 1149 | Rome II |      171 (14.9) |

## Approximately 25% of Sufferers Seek Care

**1. Stewart WF, et al. *****Am J Gastroenterol*****. 1999;94:3530-3540.**
**2. ****Drossman DA, et al. *****Dig Dis Sci.***** 1993;38:1569-1580.**
**3. Harris Interactive Study, Wave 2. Data on file. ****4. Paré P, et al. *****Am J Gastroenterol.***** 2001;96:3130-3137.**

**53**

| Population | n | Criteria | Prevalence, n (%) | Sought care,
% |
| --- | --- | --- | --- | --- |
| US1 | 10,018 | Rome I |    461 (4.6) | NA |
| US2 | 5430 | Rome I |    195 (3.6) | 22 |
| US3 | 15,183 | Rome II | 2429 (16) | 24 |
| Canada4 | 1149 | Rome II |      171 (14.9) | 26 |

## Constipation Affects All Age Groups

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**Canadian population.**
**Paré P, et al. *****Am J Gastroenterol*****. 2001;96:3130-3137.**

**N = 1149**

**n = 378**

**n = 367**

**n = 217**

**n = 187**

## Epidemiology

**Chronic constipation is common**
**Slightly more common in women **
**F/M ratio = range 1.3 to 2.5**
**Affects all age groups**

**Stewart WF, et al. *****Am J ******Gastroenterol*****. 1999;94:3530-3540.**
**Paré P, et al. *****Am J Gastroenterol*****. 2001;96:3130-3137.**
**Sandler RS, et al. *****Dig Dis Sci*****. 1987;32:841-845. **

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## Profile of a Typical Chronic Constipation Patient in My Practice

**Generally female**
**Symptomatic for > 10 yr**
**Majority have tried lifestyle changes, fiber, and OTC laxatives prior to seeking care**
**Manages condition with multiple therapies**
**Most often referred by a primary care physician **
**Copes with condition, but is not completely satisfied**

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## Constipation Can Have a Negative Impact on Quality of Life

**In Olmstead County, Minnesota, people with CC reported significant impairment in QoL on SF-36 scale (n = 126)****1**
**In Canada, people with self-reported or Rome II constipation had significantly worse SF-36 scores than the normal population (n = 472)****2**
**In Australia, people with constipation had significantly worse SF-12 scores on both mental and physical scales (n = 227)****3**

**1. O’Keefe EA, et al. *****J Gerontol A Biol Sci Med Sci*****. 1995;50:M184-M189.****2. Irvine EJ, et al. *****Am J Gastroenterol*****. 2002;97:1986-1993. ****3. Koloski NA, et al. *****Am J Gastroenterol*****. 2000;95:67-71. **

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## Constipation Significantly Impacts Healthcare Utilization

**5.7 million constipation-related outpatient visits annually****1,2**
**4.1 million physician office-based visits **
**991,000 emergency room visits**
**587,000 hospital outpatient visits**
**$2752/patient for tertiary care evaluation****3**

**1. National Ambulatory Medical Care Survey, 2001. www.cdc.gov**
**2. National Hospital Ambulatory Care Survey, 2001. www.cdc.gov**
**3. Rantis PC Jr, et al. *****Dis Colon Rectum*****. 1997;40:280-286.**

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## Goal of Therapy in Chronic Constipation

**The goal of therapy is to improve GI function in order to provide relief of key symptoms: **
** ****Straining**
** ****Hard/lumpy stools**
** ****Feeling of incomplete evacuation**
** ****Infrequent bowel movements**
** ****Bloating/fullness**

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## Medications Commonly Used for Constipation

**Fiber **
**Laxatives**
**Osmotic laxatives **
**Stimulant laxatives**
**Enemas or suppositories**
**Miscellaneous**

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**Adapted from Lembo A, et al. *****N Engl J Med*****. 2003;349:1360-1368.**

## Efficacy of Current Treatments for Chronic Constipation 

**Variable treatment responses **
**For the constellation of constipation symptoms, efficacy not evaluated or demonstrated with most agents**
**Most agents indicated for ≤ 2 wk of treatment**

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**Petticrew M, et al. *****Qual Health Care*****. 2001;10:268-273. **
**Jones MP, et al. *****Dig Dis Sci*****. 2002;47:2222-2230. **
**Rao SS. *****Gastroenterol Clin North Am*****. 2003;32:659-683.   **

## Limitations of Current Treatmentsfor Constipation

**Worsening of some constipation symptoms**
**Bloating and gas**
**Cramping, abdominal pain/colic**
**Development of complications **
**Diarrhea, hypovolemia **
**Metabolic disturbances**
**Other adverse effects**
**Interference with concomitant drug absorption**
**Structural changes in gut mucosa**
**Abuse potential (dependency)**
**Diminished therapeutic effect over time **

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**Xing JH, et al. *****Dis Colon Rectum*****. 2001 Aug;44:1201-1209.  Garcia MC, et al. *****Tenn Med*****. 2002 Aug;95:334-336.  Chaussade S, et al. *****Aliment Pharmacol Ther*****. 2003 Jan;17:165-172.  Riley SA, et al. Br J Clin Pharmacol. 1992 Jul;34:40-46.  Gattuso JM, et al. *****Drug Saf*****. 1994 Jan;10:47-65.  Wald A. *****J Clin Gastroenterol*****. 2003;36:386-89. Duncan A, et al. *****Eur J Gastroenterol Hepatol*****. 2001;13:599-601. **

## Physicians Believe Patient Satisfaction With Current Therapies Is Low

**Yes****18%**

**Are your patients ****completely satisfied?**

**No****82%**

** ****Schiller LR, et al. *****Am Coll Gastroenterol.***** 2004, *****abstract***** *****submitted*****.**

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**n = 311**

**60% of physicians agreed that they do not have adequate products**
**90% of physicians wanted better treatment options**
**Physicians cited “frustration with current treatments” one of the top ****3 reasons patients state for seeking care**

| Reasons for dissatisfaction* |  |
| --- | --- |
| Efficacy | 93% |
| Safety/side effects | 57% |
| Other (ie, taste, compliance) | 27% |

***Not mutually exclusive.**

## Many Constipation Patients Are Not Satisfied With Available Treatments

| Reasons for dissatisfaction* 1 |  |
| --- | --- |
| Efficacy | 82% |
| Safety/side effects | 16% |
| Other (ie, taste, compliance) | 17% |

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**1. Schiller LR, et al. *****Am Coll of Gastroenterol.***** 2004, *****abstract***** *****submitted*****.**
**2. Irvine EJ, et al. *****Am J Gastroenterol*****. 2002;97:1986-1993. **
**3. Ferrazzi S, et al. *****Can J Gastroenterol*****. 2002;16:159-164. **

***Not mutually exclusive.**

**Yes****53%**

**Are you completely****satisfied? ****1**

**No****47%**

**n = 557**

## Chronic Constipation:A Condition in Need of a Better Approach

**Characterized by a constellation ****of symptoms**
**High resource utilization and significant negative impact on patients’ lives**
**Current pharmacologic agents have limitations**
**Many patients are not satisfied with available therapies**
**Better treatment options are needed**

**C**