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Update on the Management of Chronic Idiopathic Constipation
Brian E. Lacy, MD, PhD, FACG
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Update on the Management of Chronic Idiopathic Constipation

Brian E. Lacy, MD, PhD, FACG
Chronic idiopathic constipation is a functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation, affecting 35 million adult Americans, resulting in more than millions of physician visits annually. Symptoms of constipation vary from patient to patient and impact all age groups and patient populations in the United States. The definition of constipation was previously not well specified, beyond stool frequency, and has been revised to incorporate the patient perspective and experience in addition to specific criteria created by the Rome Foundation. In the absence of red-flag (alarm) symptoms, and with a normal physical (including rectal) examination, patients can initially be empirically treated for their symptoms of chronic constipation assuming adequate follow-up is arranged. Unfortunately, both patients and healthcare providers have documented unmet needs with currently available therapeutic options, thus prompting research for new agents with novel mechanisms of action that are both efficacious and safe.
 
Am J Manag Care. 2019;25:-S0
Introduction
Chronic idiopathic constipation (CIC), previously labeled as functional constipation, is a highly prevalent disorder reported to healthcare providers.1 Symptoms of constipation can vary by patient but are observed in all age groups and patient populations across the United States, with millions of physician visits occurring annually.2,3 CIC is a functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. Patients with CIC should not have an underlying anatomic or structural abnormality as the cause of their symptoms.1,4 It is recommended that patients with CIC be differentiated from patients with irritable bowel syndrome (IBS),4 although there is significant overlap in the physiology and treatment of IBS-constipation (IBS-C) and CIC.5-7 

An exact measure of CIC incidence and prevalence is difficult to obtain, as many published studies rely on patient self-reports, although clinical studies have assessed the epidemiology of CIC using a wide variety of questionnaires.8 With these caveats in mind, it is estimated that approximately 35 million adult Americans have CIC, and 16 of 100 adults have symptoms of constipation.2,9 A 2011 systematic review of studies measuring the prevalence of constipation in countries throughout the world reported a pooled prevalence of 14% for patients with the primary definition of CIC in each study.1 CIC has a significant impact on the healthcare system, accounting for 3.92% of all ambulatory care visits in the United States in 2014.3 Furthermore, although CIC has been found to affect all individuals in the general population, it disproportionately affects women (odds ratio [OR], 2.2 female to male ratio), the elderly (OR, 1.4), and individuals of lower socioeconomic status (OR, 1.3).1,8,10,11 Other common risk factors of constipation include reduced caloric intake, sedentary lifestyle, decreased fiber intake, and usage of anti-inflammatory agents.12,13

Guidelines for the treatment of CIC are available from the American College of Gastroenterology and the Rome Foundation.4 The management of CIC is multifaceted and focuses on empiric therapy for many patients and ruling out secondary causes of constipation in others, with the overall goal of developing an individualized treatment plan that provides multisymptom relief. The purpose of this document is to review underlying mechanisms in the development of CIC and to provide an update on currently available therapeutic agents.

Normal Physiologic Function of the Colon
To fully understand the pathophysiology of CIC and its treatment, it is important to briefly review the normal physiology of the colon. A healthy colon utilizes peristalsis and mass movements (propulsive activity) to move contents through the colon, which then leads to defecation.14 These mass movements occur primarily as a result of high amplitude propagating contractions (HAPCs) due to the contraction of colonic smooth muscle and neuronal signaling via the myenteric nerve plexus.15,16 A healthy individual generally experiences 6 HAPCs per day on average,17 usually after awakening and after meals. This is in contrast to those with CIC who may have fewer, shorter, or lower amplitude HAPCs.18,19 HAPCs are considered a driving event in the normal physiology of the colon and defecation; some therapeutic agents have been shown to increase the frequency and amplitude of HAPCs, which may account for their therapeutic effects.20,21

Serotonin, also known as 5-hydroxytryptamine (5-HT), plays a major role in normal colon function with respect to gastrointestinal (GI) motility and sensation.11 5-HT is the most common neurotransmitter synthesized and released by the GI tract, primarily by enterochromaffin cells, which produce the majority of serotonin found in the body (approximately 95%).15,16,22 Although the role of 5-HT in normal colonic activity is controversial, 5-HT does mediate peristalsis by binding to 5-HT receptors.15 When neurotransmitters, such as acetylcholine, are released, smooth muscle contraction occurs in the GI tract on the orad side of the luminal contents and moves forward with the end goal of defecation.23 In addition to peristalsis, the colon also is responsible for the management of intestinal fluid and electrolyte content via reabsorption (approximately 1-2 L of fluid/day). Increasing fluid content in the GI tract through the use of secretagogues is a newer therapeutic area of interest.16

Clinical Presentation and Diagnosis
The term constipation is used liberally, referring to multiple symptoms including hard stool, excessive straining, infrequent bowel movements, bloating, and the feeling of difficult or incomplete evacuation.11 Due to the lack of a proper meaning of the term, there is often confusion and mischaracterization of constipation by both patients and physicians.24 The definition of constipation has been revised in recent years to focus less on stool frequency, thereby not only addressing the patient’s perspective, but to also acknowledge constipation as more of a syndrome with overlapping features.25 For example, expert consensus from the current Rome IV criteria (Table 14) addresses functional bowel disorders as a spectrum of GI disorders, as opposed to isolated entities.25

Furthermore, experts recognize that although there are specific diagnostic criteria for each functional GI disorder (eg, dyspepsia, IBS, CIC), symptoms are nonspecific and frequently overlap, making it difficult to accurately distinguish between each disorder.25 The Rome IV criteria indicate that it is common for patients to transition between one bowel disorder, or predominant symptom, to another (eg, CIC to IBS), which may occur normally as part of the disorder, due to treatment, or a combination of the two.25

A survey by Johanson et al found the most frequent symptoms reported by patients with CIC to be straining (79%), hard stool (71%), abdominal discomfort (62%), bloating (57%), feelings of incomplete bowel evacuation after a bowel movement (54%), and infrequent bowel movements (57%).26 As discussed, it is common for patients with bowel disorders to have overlapping symptoms, and CIC is commonly confused with IBS-C.8 For example, patients with CIC may report symptoms of abdominal pain and bloating, but those symptoms typically are milder and do not predominate, as opposed to those in patients with IBS-C.4

The diagnosis of CIC begins with a comprehensive review of a patient’s history (dietary, medical, surgical, and psychological) and a careful physical examination. This should include a digital rectal exam, which may identify pelvic floor dyssynergia in younger patients or an occult malignancy in older patients. Although CIC and IBS-C are some of the most common disorders associated with chronic constipation (CC), there are a number of secondary causes of CC (eg, medications, mechanical obstruction, metabolic disorders) (Table 2).8,11,27 If a patient presents with any red-flag symptoms, such as sudden weight loss or rectal bleeding, further evaluation is necessary to rule out potentially more serious etiologies (eg, malignancy). When appropriate, practitioners can order diagnostic tests (preferably when the patient is laxative free) that assess stool frequency, daily stool weight, colonic transit, and anorectal function, to exclude other etiologies, such as slow transit constipation and pelvic floor dyssynergia.4 In practice, it can be challenging to distinguish between IBS-C and CC or even the different types of CC based on symptoms alone; thus, additional testing may be necessary. For example, significant straining is indicative of defecatory disorders (DD) but not diagnostic. Tests such as an anorectal manometry and a balloon expulsion test may be useful to confirm a diagnosis of DD, although these tests are not always readily available.8 In addition, the Bristol stool form scale28 (Figure4) can be used to monitor changes in intestinal function and at the extremes of the scale,29 it can be used as a surrogate for colonic transit.8 Once secondary etiologies have been ruled out, the Rome IV criteria can be used to diagnose a patient with CIC.4 The Rome IV criteria are shown in Table 1; the diagnosis requires the onset of symptoms at least 6 months before presentation, with symptoms present for the previous 3 months.4

There are 3 main subtypes of CC: normal-transit constipation (NTC), slow-transit constipation (STC) or “colonic inertia,” and DD, such as pelvic floor dyssynergia.8 Identifying the subtype is important, as it helps facilitate management decisions, such as medications for NTC and STC or pelvic floor therapy (physical therapy with biofeedback) for DD. In a tertiary referral practice involving approximately 1400 patients with constipation symptoms, about 5% were diagnosed with STC, 65% with NTC, and 30% with DD.30

Several limitations should be highlighted concerning the 3 subtypes of CC, as there is a growing body of evidence suggesting that these subtypes are an oversimplification of the categorization of CIC.18,24,31-33 For example, symptoms of STC and DD differentiate these 2 conditions poorly24 and they frequently overlap.33,34 Additionally, delayed colonic transit and DD are commonly seen among individuals with IBS.31,32 Therefore, treatment for CIC should be individualized, taking into account prior treatments and the real possibility that CIC may be multifactorial in origin. Selection of a therapeutic agent to treat symptoms of constipation should be a joint decision between the patient and provider that takes cost, tolerability, safety, patient preference, lifestyle considerations, and other pertinent clinical information into consideration.

Management of Chronic Idiopathic Constipation
Initial treatment of CIC begins with patient education, medication review (discontinuing any agents that could slow colonic transit), and lifestyle modifications (eg, increased dietary fiber to 20-30 g/day, physical activity, and adequate hydration). In addition, it is also helpful to create a routine schedule for using the lavatory. Using a toilet that is closer to the floor or adding a device to elevate the feet can also help ease straining.4



 
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