The guideline development was based upon the adaptation method because research evidence was limited in Korea; an organized multidisciplinary group involving the Korean Society of Coloproctology and the Korean Society of Radiology carried out systematic review and series of evidence-based evaluations. In contrast with the 2011 constipation treatment guidelines, the diagnosis of chronic constipation and new medicines were added. Following the findings of recent studies, we properly adjusted the grades of recommendation. An expert methodologist (E.S.S.) from the Korean Academy of Medical Science was involved in revising the guidelines to ensure the process in a scientific and standardized manner.

To determine the clinical questions that should be included in the treatment guidelines, we designed an investigation table in accordance with the “PICO” principles: P (population) was defined as constipation patients or clinical characteristics of constipation, I (intervention) was defined as diagnostic or therapeutic intervention, C (comparison) was defined as the control group, and O (outcome) was defined as the effectiveness of the diagnosis or treatment. We tried to include these four principles into clinical questions. After collecting investigation tables that contained clinical questions, we prioritized them through structural debates.

In July 2013, we used the following electronic databases to search for relevant information and preexisting guidelines: MEDLINE, MEDLINE Systematic Review, MEDLINE Clinical Study, OVID MEDLINE, EMBASE, the Web of Science, SCOPUS, the Cochrane Library, the National Guideline Clear-inghouse, Guidelines International Network, Google Scholar, KoreaMed, MEDRIC, KISS, and Korea National Assembly Electronic Library.

The search words were constipation-related index words (“constipation” OR “dyschezia” OR “anismus” OR “dyssynergic defecation” OR “obstructive defecation”) and guideline-related index words (“guideline” OR “guidelines as topic” OR “guideline adherences” OR “practice guideline” OR “practice guidelines as topic” OR “clinical guideline” OR “clinical practice guideline” OR “consensus” OR “recommendation” OR “workshop” OR their combination) (Appendix).

The criteria for selecting preexisting guidelines were as follows: (1) evidence-based, (2) written in Korean or English, (3) published between 2002 and 2013, (4) targeted at adults aged 19 or older, (5) latest revised versions, and (6) agreed upon by experts and external review.

Exclusion criteria were as follows: (1) guidelines not made in an evidence-based manner, (2) only targeted at inpatients, (3) outdated, and (4) addressed over-the-counter drugs (Fig. 1).

The first literature selection was performed by a medical librarian (E.A.J.), who is an expert in systematic literature reviews. She performed the search process as mentioned above, organized the findings with Endnote (Endnote X7; Thomson Reuters, New York, NY, USA) and Excel (Excel 2010; Microsoft, Redmond, WA, USA), and removed duplicate documents.

A second review was performed by reviewing the titles and abstracts from the first review to select articles that satisfied both the inclusion and exclusion criteria. Then, 2 independent reviewers read selected full articles for content validity. When there was agreement between them and the article was suitable for this adaptation, the article was selected. If the 2 reviewers could not reach an agreement, a chairperson was engaged to reach consensus. Ultimately, six preexisting guidelines were selected as seed guidelines (Fig. 1).

We used AGREE II, which is an internationally recognized method for developing guidelines, to evaluate the quality of the seed guidelines for adaptation. Each seed guideline was evaluated by 2 reviewers; we provided lectures and workshops to minimize the variation in scores across reviewers and to enhance their understandings of AGREE II. For this process, we followed the Korean-AGREE II method, developed by the Steering Committee for Clinical Practice Guidelines of the Korean Academy of Medical Sciences. The Korean-AGREE II was tested for validity through official consensus, and was shown to be valid.¹⁵ In the workshops, we selected one guideline, and all reviewers evaluated it using AGREE II, compared our findings with those of an experienced member for the Steering Committee for Clinical Practice Guidelines of the Korean Academy of Medical Sciences, and adjusted our findings based on the member’s feedback. Two reviewers assessed each guideline, and reevaluated any guidelines for which the difference in scores was 3 points or higher on any 5 items or more. We standardized scores for each domain, created a distribution chart, and then selected 6 seed guidelines by comparing the scores in each domain (Fig. 2). We prioritized rigor of development in the selection criteria, and only selected guidelines with a rigor score of at least 50 points.

After selecting seed guidelines, we prepared a recommendation matrix for data extraction to extract recommendations for each subtitle based on the clinical question (PICO; Table 1). We extracted recommendations with references that best fitted the clinical questions from the selected guidelines, created a matrix based on commonly shared contents and referred articles, and developed a single set of proposed recommendations.

To develop a rating system reflecting the level of evidence for each recommendation, we conducted a comprehensive quality evaluation that included the planning method, quality, and consistency of the study based on Grading of Recommendations Assessments, Development, and Evaluation criteria for high overall quality of evidence across outcomes; this consisted of three levels (Table 2).^16,17

Recommendations were graded as either strong or weak. A strong recommendation was defined as a recommendation where positive effects are much greater than negative effects, expected effects were likely when users followed recommended instructions, and the research results were predicted not to change in the future. A weak recommendation was defined as a recommendation with inconsistent results that might not be reproducible in future studies.

For the adoption of recommendations, we structured a panel of experts that represented a group of users and specialists and used the Delphi method in the same way as for the development of updated gastroesophageal reflux disease guidelines.¹⁸

In total, 28 persons participated in the first round of Delphi consensus: 26 gastroenterologists, one surgeon from the Korean Society of Coloproctology and one expert from the Steering Committee for Clinical Practice Guidelines of the Korean Academy of Medical Sciences. The first draft included 41 recommendations: 4 concerning the definition and risk factors of chronic constipation, 8 regarding diagnoses, and 29 regarding treatments. Of the 41 draft recommendations, 37 were selected, whereas 4 were rejected. After the second Delphi round by e-mail voting, a final total of 37 recommendations were adopted.

The editorial supervision committee consisted of 4 members. Three (H.K.J., J.E.S., and T.H.L.) edited and proofread the first draft of the guidelines. One external expert (S.J.M.) engaged in independent peer review for verification purposes, and to enhance the balance and completeness of the guidelines.

Developing treatment guidelines in an objective and scientific manner is challenging because evidence-based research is insufficient in Korea. However, it is not realistic to simply accept guidelines developed in other countries because these may have different medical systems and epidemiological, clinical, and ethical settings. Considering these limitations, we used adaptation methods. These evidence based guidelines were developed to help clinicians enhance the quality of medical services and to allow patients to receive standardized and consistent clinical management. Therefore, this guideline may be different with the criteria for quality evaluation related to medical insurance.

These revised guidelines will be accessible through the website of the Korean Society of Neurogastroenterology and Motility (http://www.jnmjournal.org). We plan to promote the guidelines using the information center for clinical treatment guidelines established by the Korean Academy of Medical Science and will continue to promulgate them at relevant academic conferences, seminars, and workshops. These guidelines will be revised every 3–5 years to reflect new data pertaining to the development of diagnostic and therapeutic methods and the accumulation of additional research findings.

As confirmed by a written pledge by participants, the development of these guidelines was made without external financial support and there were no conflict of interest for the participants involved in this research process, and it was verified by written consents.

Stool form according to the Bristol Stool Form Scale (BSFS) is a useful visual aid (Fig. 3).³⁷ It uses simple visual illustration that is easily understood by patients, enabling them to recognize stool form and consistency. The BSFS is a reliable indicator of CTT³⁸ and particularly useful in patients reporting some discrepancy between the frequency of bowel movements and stool hardness.²⁶ Some patients complain of having constipation with a normal frequency of bowel movement and hard or lumpy stool, but in some cases, patients consider constipation to be having rare bowel movements with normal stool consistency. No correlation has been observed between stool frequency and measured transit in constipated or healthy adults.³⁸ In constipated adults, stool form correlated well with colon transit, but this correlation was not detected in healthy controls. Thus, history taking pertaining to stool form is a simple and useful way to estimate CTT in constipated patients.

Basically, testing to rule out organic disease should be left to the judgment of the treating physician, based on the constipation symptoms, the impact on the patient’s quality of life, and the presence of risk factors or alarm features obtained from the history and physical examination.¹⁹ Routine extensive diagnostic testing is not recommended for chronic constipation. A systematic review noted that no reported study has assessed routine blood tests or abdominal X-rays in patients with constipation.³⁹ A complete blood cell count can be performed.²² Although fasting serum glucose, thyroid-stimulating hormone, and calcium levels are often measured, the diagnostic utility and cost-effectiveness of these tests have not been rigorously evaluated and are probably very low.⁴⁰ However, colonoscopy should be performed in all patients with alarm symptoms.²² In subjects with no alarm symptoms, the rate of adenoma or colon cancer by colonoscopy has been found to be similar between groups reporting simple constipation and asymptomatic populations undergoing screening.³⁹

Economic analysis have suggested that screening tests for colon cancer is cost-effective,⁴¹ but no formal economic analysis of the evaluation of constipation has been reported. Because patients with constipation are at similar or higher risk (newly-onset constipation or older age) for colon cancer, a colonoscopy is likely to also be cost-effective in patients with constipation.⁴²

Testing for colon cancer with colonoscopy should be considered for patients aged 50 years or older who have not undergone an age-appropriate colon cancer screening procedure since the onset of constipation.^19,22,26,43 However, routine colonoscopy is not warranted for most patients with chronic constipation, because the prevalence of colonic neoplasms at colonoscopy is comparable to that in patients without chronic constipation.⁴⁴

Digital rectal examination (DRE) is an important physical examination for the diagnosis of constipation. DRE can detect stool in the rectal vault, rectoanal masses, hemorrhoids, anal fissures, rectal prolapse, and rectoceles that cause secondary constipation.⁴² It is also useful for identifying defecatory disorders. DRE proceeds sequentially and precisely as shown in Table 3.⁴⁵ In short, if there is inappropriate perineal descent, absence of anal sphincter relaxation or paradoxical muscle contraction, it suggests the presence of defecatory disorders. For the diagnosis of dyssynergia, a carefully performed DRE has shown 75% sensitivity and 87% specificity when conventional anorectal manometry (ARM) was adopted as the reference.⁴⁶ DRE has also shown 93.2% sensitivity and 91.0% positive predictive value in detecting dyssynergia compared with high-resolution anorectal manometry (HRAM).⁴⁷ DRE can be used as a bedside screening test for the diagnosis of dyssynergia and is an effective diagnostic method that enhances decisions regarding additional anorectal function tests and treatment modalities in patients with constipation. However, a normal DRE does not exclude defecatory disorders.²²

Anorectal physiologic tests are not routinely recommended for diagnosis of chronic constipation.²² ARM is performed in patients with constipation who fail to respond to laxatives for the diagnosis of defecatory disorders. However, it may be considered earlier in cases of strongly suspected defecatory disorders.^22,48 ARM includes resting anal sphincter pressure, squeezing anal sphincter pressure, rectoanal inhibitory reflex, rectal and anal pressure during attempted defecation, rectal sensation, and rectal compliance. The main finding of a defecatory disorder is absent or inadequate relaxation or paradoxical contraction of the anal sphincter during straining, sometimes associated with absent or inadequate increase of rectal pressure. ARM results should be interpreted carefully because the methods of ARM have not yet been standardized, and the results may differ according to measuring methods and equipment in each center. HRAM is generally correlated with traditional ARM.⁴⁹ ARM is useful for diagnosing defecatory disorders in patients with constipation, but there is no gold standard for the diagnosis, and abnormal results may occur in the asymptomatic general population. Thus, a comprehensive evaluation with other anorectal physiological tests, including balloon expulsion test (BET), imaging techniques, and perhaps electromyography, is necessary for diagnosing defecatory disorders.²

The BET evaluates defecatory function during a simulated defecation and can identify patients with abnormal defecation. It is a simple and inexpensive test. However, it is not supported by placebo-controlled trials and has not yet been standardized. In recent studies, a “normal” result is defined as balloon expulsion within 1 minute after attempted defecation.⁴⁸ If the balloon is not expelled, it suggests the possibility of defecatory disorders. In one study, BET was 87.5% sensitive and 89% specific with positive and negative predictive values of 64% and 97% for the diagnosis of defecatory disorders, respectively.⁵⁰ It was concluded that a negative test was useful for identifying patients who do not have dyssynergia. However, Rao et al^39,51 found that many patients with dyssynergia could expel the balloon, and they expressed the view that a normal test could not exclude the possibility of a defecatory disorder. BET can be helpful in predicting defecatory disorders, but other rectoanal function tests should be performed to confirm a diagnosis.⁴³

Defecography is a type of radiological imaging in which the mechanism of a patient’s defecation is visualized in real time using a fluoroscope. The anatomy and function of the anorectum and pelvic floor are studied dynamically at various stages during defecation. Thus, defecography is considered after inconclusive results of ARM and rectal balloon expulsion in chronic constipation with an inadequate response of therapeutic trials.⁴² Defecography is particularly useful for identifying anatomical abnormalities, such as paradoxical contraction of the puborectalis muscle, a rectocele, rectoanal intussusception, and complete external rectal prolapse that may be amenable to surgical intervention.^23,52–56

Barium defecography is commonly used, although the test or technique is incompletely standardized and it has limited reproducibility in terms of anorectal angle measurements.⁵⁴ Internal consistency of defecographic parameters has been reported to be good (α = 0.78), but agreements between each defecographic parameter and each test of ARM and electromyography have all been shown to be poor.⁵⁷ Magnetic resonance (MR) defecography avoids radiation exposure and is better for visualizing the bony landmarks that are necessary for measuring pelvic floor motion than barium defecography. Its measurements are reproducible among observers.^58,59 However, MR defecography is an expensive test and is not commonly available at hospitals.

Endovaginal or endoanal sonography can be used to evaluate pelvic floor anatomy in patients with evacuation dysfunction.⁶⁰ Endovaginal sonography is recommended as an alternative to defecography or MR imaging.⁶¹ Endoanal 3-D reconstructed sonography can provide detailed abnormalities, such as anal sphincter defects, fistulous tracts, and submucosal invasion in early anorectal cancers.⁶⁰

Colonic transit is most commonly and inexpensively measured using radiopaque markers. Kolomark (M.I.Tech, Pyeongtaek, Korea)⁶² and Sitzmarks (a capsule containing 24 markers; Konsyl Pharmaceuticals, Texas, USA)⁶³ are commonly available markers in Korea. Several methods have been suggested and the multiple capsules technique is one of the most popular methods to measure the CTT. This technique requires the ingestion of 1 capsule a day for 3 days, followed by abdominal X-rays on day 4 and 7; a normative value for total CTT in healthy Korean adults is 22.3 ± 16.1 hours in males and 30.1 ± 21.4 hours in females.⁶⁴ There are differences in CTTs by age, gender, race, and methodology. Western people and women have a longer transit time.^62–64 Segmental CTT is believed to differentiate between STC and pelvic floor outlet obstruction.⁴³ CTT can be readily performed at an early stage in the diagnostic process of chronic constipation, because CTT is easily measured in many institutions, in contrast with other tests such as ARM, defecography, or electromyography.

However, lack of standardization in the procedure makes it difficult to compare results among hospitals,^63,65 and the test is less reproducible in defecatory disorders and colonic inertia.⁶⁶ As more than 50% of patients with defecatory disorders show slow CTT, measurement of colon transit alone cannot exclude a defecatory disorder. Even if a defecatory disorder coexists with slow colonic transit, this finding does not alter a treatment modality such as biofeedback as the main approach for the patient. Some consider that colon transit should be performed when ARM, BET, or defecography show normal findings.⁴² Thus, the clinician should consider which tests are to be performed in patients with chronic constipation according to the main symptoms and the tests available at each institution.

Radiographic and scintigraphic methods correlate well, and scintigraphy requires scanning for 24 or 48 hours versus 5–7 days for completing a radiopaque marker study.⁶⁷ In patients with constipation, the correlation between colonic transit by using radiopaque markers and the wireless motility-pH capsule is reasonable (correlation coefficient = 0.7).⁶⁸

Data regarding the effectiveness of physcial activity in alleviating constipation have been variable. In a large survey conducted with 39,532 women, the odds ratio for constipation among women who reported lower to moderate physical activity was significantly lower than that among sedentary women in all three aged cohorts (young, middle aged, and older). Compared with sedentary young, middle aged, and older women, those with moderate physical activity showed significant odds ratios (0.70, 0.75, and 0.82, respectively).⁶⁹ Another survey showed that constipation in elderly patients was most clearly associated with poor mobility.⁷⁰ Elderly patients were thought to have an increased risk of constipation depending on their level of activity.³⁵ More frequent bowel movements may be caused by running.⁷¹ These findings suggest that low-to-moderate levels of exercise are associated with benefits for constipated patients. A study of colonic motility using a solid state manometric probe showed that colon phasic activity was decreased during exercise and propagated activity was enhanced after exercise.⁷² A Korean study showed that moderate or high levels of physical activity shortened CTT in females, but not in males.⁷³

However, the average of total physical activities was not significantly different in normally active subjects with and without constipation.⁷⁴ The effect of moderate physical exercise on bowel transit time has been questioned in healthy subjects.^75–78 In a small group of chronically constipated patients who did an extra hour of exercise 5 days per week for 4 weeks, there was no improvement in the number or consistency of their bowel movements or the degree of straining required for defecation.⁷⁹ Increased physical activity might offer symptomatic improvement, especially in elderly constipated patients with low levels of physical activity. It is not clear that exercise helps younger constipated patients with normal activity. Recently, moderate-to-vigorous intensity physical activity (20–60 minutes, 3–5 days per week) has been shown to improve symptoms and quality of life in IBS.⁸⁰ Taken together, increased physical activity should still be recommended to patients because it improves quality of life and has other health benefits unrelated to chronic constipation.

Dietary fiber undergoes parital or total fermentation in the distal small bowel and colon, leading to the production of short-chain fatty acids and gas, thereby affecting gastrointestinal function and sensation.⁸¹ A prospective cohort study showed that higher daily fiber intake significantly reduced the likelihood of self-reported constipation.⁸² A recent meta-analysis concluded that dietary fiber intake can clearly increase stool frequency in patients with constipation.⁸³ Naturally occurring fiber types include soluble highly fermentable oligosaccharides (eg, fructo-oligosaccharides and galacto-oligosaccharides), soluble highly fermentable fiber (eg, resistant starch, pectin, guar gum), intermediate soluble fermentable fiber (eg, psyllium and oats), insoluble slowly fermentable fiber (eg, wheat bran, fruit, and vegetables), and insoluble non-fermentable fiber (eg, cellulose and sterculia).⁸¹ Good laxative effects were observed in intermediate soluble fermentable fibers, insoluble slowly fermentable fibers, and insoluble non-fermentable fibers.⁸¹ A recent study showed that treatment with dried plums resulted in a significant increase in the number of complete spontaneous bowel movements (CSBMs) and stool consistency, compared with treatment with psyllium.⁸⁴ However, it is not clear that dietary fiber improves stool consistency, treatment success, laxative use, or painful defecation.⁸³

Dietary fiber appears to be effective in relieving mild to moderate, but not severe constipation.⁸⁵ Two Korean studies reported that dietary fiber is effective in the management of constipation without adverse events.^86,87 Increased dietary fiber intakes for adults with chronic constipation is associated with considerable cost savings, potentially exceeding $12 billion in the US population.⁸⁸ There is a lack of evidence supporting the notion that dietary fiber is effective for individual constipation subtypes (obstructive, metabolic, neurological, diet-related, myogenic, drug-related, and pelvic floor dysfunction).⁸¹ Occasionally, patients will experience marked worsening of their constipation-related symptoms with fibers. When this occurs, severe STC or defecatory disorders should be strongly considered.⁸⁹ It is reasonable to prescribe osmotic laxatives to avoid cramping abdominal pain before initiating an increase in dietary fiber, especially in patients with significant fecal stasis.⁸¹

Bulking agents are fiber supplements including psyllium (ispaghula husks), calcium polycarbophil, methylcelluolose, and bran. Among them, psyllium has the highest level of evidence with regard to the treatment of chronic constipation. Compared with placebo, bulking agents (especially psyllium) resulted in improvements in global symptoms, straining, pain on defecation, and stool consistency, an increase in the mean number of stools per week, and a reduction in the number of days between stools.⁹⁰ A randomized crossover study of 4 weeks treatment with psyllium showed that stool frequency, weight, consistency, and pain on defecation improved significantly on psyllium; however no effect was observed with respect to colon transit or ARM parameters.⁹¹ A single-blind, randomized, crossover study of 4 weeks treatment with psyllium improved gut transit time significantly in constipated patients with pelvic floor dysynergia, compared with a placebo group.⁹² However, there was no significant differences in stool frequency, consistency, or weight between the groups. In a randomized, double-blind, parallel study of 170 constipated patients, treatment with psyllium for 2 weeks significantly improved stool weight and freqeuncy (in treatment week 2), compared with docusate.⁹³ Evidence from nine studies^91–99 of psyllium showed that it apparently improved stool frequency, but there were conflicting results regarding stool consistency and transit time. No signficant difference in advese events was observed between the psyllium group and the comparison group. However, the duration of treatment with psyllium in these studies was less than 8 weeks, although the therapeutic effect would be expected to be maintained for a long time.

Potential adverse effects of bulking agents include gas, bloating, esophageal obstruction, colonic obstruction, and calcium and iron malabsorption. There is a relative lack of data available for making a recommendation for calcium polycarbophil. Some patients tend to prefer calcium polycarbophil to psyllium with respect to bloating.¹⁰⁰ Studies of methylcellulose and bran were lacking appropriate controls and were of low methodological quality.¹⁰⁰

Inadequate intake of dietary fiber is believed to contribute to constipation, and many guidelines recommend that increasing dietary fiber intake should be the first-line step in the management of constipation.^9,22 Despite the limited evidence for the benefits of this approach in constipated patients with inadequate fiber intake, a bulking agent can be effective in their symptomatic improvement. However, psyllium is not effective in severe STC or defecatory disorders. The use of osmotic laxatives may be favored before initiating treatment of bulking agents to avoid abdominal discomfort, bloating, and pain in a subset of constipated patients.⁸¹

Contraindications for bulking agents include hypersensitivity to any included components, fecal impaction, and bowel obstruction. When bulking agents are used, inadequate fluid intake can result in abdominal gas or bloating, which may then paradoxically predispose the patient to bowel obstruction.¹⁰¹ The elderly in particular may have insufficient fluid intake, which may predispose them to fecal impaction and bowel obstruction. Fluid intake alone has not been reported to be effective as a treatment for constipation,¹⁰² but it may benefit patients who are dehydrated.

Magnesium salts have been widely used in mild-to-moderate constipation because of their low price and ready availability. Only one study of 64 institutionalized older patients (≥ 65 years) with chronic constipation showed that magnesium hydroxide resulted in significant improvements in bowel movements, stool consistency, and decreased use of additional laxatives, compared with a bulking agent (plantain rind) plus sorbitol.¹⁰³ Polyethylene glycol (PEG) solution plus magnesium hydroxide induced more significantly effective colonic preparation in constipated patients, compared with PEG solution alone.¹⁰⁴ In conclusion, few studies have examined the effect of magnesium hydroxide, but many clinicians believe that it improves stool frequency and consistency in patients with normal renal function.

There are no contraindications but precautions are needed with disease-related concerns such as renal impairment or neuromuscular disease.¹⁰⁵ Hypermagnesemia is characterized by progressive loss of neuromuscular, respiratory, and cardiovascular function. Increased magensium decreases impulse transmission across the neuromuscular junction, producing a curare-like effect.¹⁰⁶ Cardiovascular side effects of hypermagensemia include hypotension, conduction defects, bradyarrhythmia, and even cardiac arrest.^106,107 Because of the risk of hypermagnesemia, magnesium salts should not be used in patients with renal impairment.

Nonabsorbable carbohydrates, such as sorbitol and lactulose, which are classified as hyperosmolar laxatives, pass unchanged into the colon to be metabolized by colonic bacteria into lactic, acetic, and formic acids, with the liberation of carbon dioxide. These low-molecular-weight organic acids increase intraluminal fluid osmotically. Lactulose is composed of galactose and fructose, which can be produced by the isomerization of lactose, and is a prebiotic carbohydrate that stimulates the growth of health-promoting bacteria in the human gastrointestinal tract.¹⁰⁸ The time of onset of lactulose’s effect is between 24 and 72 hours.

Early studies that were methodologically limited showed the efficacy of lactulose in improving bowel frequency and stool consistency in patients with chronic constipation.^109,110 In a very early randomized trial, the success rate for lactulose was 80% and for the placebo, 33%, showing a significantly different success rate.¹¹⁰ A 12-week, double-blind study of elderly constipated patients also revealed that reduction in the severity of symptoms, such as cramping, griping, flatulence, tenesmus, and bloating was greater with lactulose.¹⁰⁹ Additionally, results in comparison with other laxatives, such as psyllium, sorbitol, and psyllium plus senna have been reported.^96,111 In a 4-week trial, the efficacy of lactulose and ispaghula was demonstrated, and effects were similar between the two groups. Differences were demonstrated with regard to acceptability in favor of lactulose.⁹⁶ When the efficacy of 4-week lactulose and 70% sorbitol were compared in a cross-over trial, there was no significant difference with regard to the percent of normal bowel movements, frequency or severity of symptoms such as bloating, cramping, and excessive flatulence, or overall health status.¹¹¹

An uncontrolled trial evaluating colon transit in Korean patients suffering with functional constipation demonstrated that patients with STC showed improvements in symptoms associated with acceleration of the proximal colonic transit via lactulose.¹¹²

Because lactulose is not absorbed systemically, it is not expected to be associated with an increased risk of malformations in pregnant women.¹¹³ In particular, this strength can lead to the safe application of lactulose in other patients groups, including those with encephalopathy or diabetes.

Nonabsorbable carbohydrates often cause gastrointestinal symptoms, including flatulence, intestinal cramps, nausea, and diarrhea. Although gastrointestinal side effects occur most often with lactulose due to its metabolism by colonic bacteria, these events are usually temporary.¹¹⁴ Considering that no potential serious side effects were found in patients treated with lactulose for more than 4 weeks, long-term treatment with this agent is generally regarded as safe and well tolerated.¹¹⁵

Randomized controlled trials (RCTs) including elderly populations support the efficacy of lactulose for stool frequency and consistency, but many studies of the use of these nonabsorbable carbohydrates in the elderly are limited because of small sample sizes and problems with their methodologies.^111,116,117

PEG is a nonabsorbable and nonmetabolized polymer that draws fluid into the intestinal lumen. There is reliable evidence for the use of PEG, with several well-designed placebo-controlled randomized trials demonstrating significant benefits of PEG in improving bowel frequency and stool consistency. Numerous trials have shown both electrolyte-enriched PEG and electrolyte-free PEG to be effective in patients with chronic constipation.^{115,118–127} A meta-analysis concluded that PEG treatment resulted in a highly significant increase in defecations per week over placebo.¹²⁸ In particular, a meta-analysis involving 10 RCTs found that PEG was better than lactulose with respect to the outcomes of stool frequency per week, form of stool, relief of abdominal pain, and the need for additional products.¹²⁹ PEG is poorly absorbed systemically, and does not appear to be associated with an increased risk of malformations in pregnant women.¹³⁰

Long-term administration (for more than 6 months) of daily PEG was effective, and appeared to be safe, well tolerated, and devoid of significant adverse events.¹¹⁹ While osmotic laxatives can generally cause electrolyte disturbances, volume overload, or dehydration, and these medications should be used with caution in patients prone to renal insufficiency or cardiac abnormalities,¹³¹ PEG is considered relatively safe in these respects. Although there have been reports about common adverse events including diarrhea, abdominal pain, nausea, and vomiting, no serious adverse events have been reported with long-term PEG treatment.¹²⁹

The majority of clinical guidelines, including Korean guidelines, have indicated the efficacy of PEG in patients with chronic constipation with high evidence and recommendations.^{9,19,42,132–134}

An open-label study evaluating the safety and efficacy of PEG given in patients who were ≥ 65 years old supported the use of PEG in elderly patients.¹³⁵ In addition, a subgroup analysis of RCTs including geriatric patient groups demonstrated better efficacy of PEG than other laxatives in normalizing stool frequency and consistency.¹¹⁵ Although PEG can frequently cause nausea, flatulence, and diarrhea, no serious side effects were reported, and PEG was well tolerated in the elderly group.

Stimulant laxatives represent a diverse class of agents derived primarily from anthraquinones (senna) and diphenylmethanes (bi-sacodyl and sodium picosulfate), and acting through direct contact with the submucosal plexus and the deeper myenteric plexus, resulting in predominantly motor but also secretory effects on the bowel. Medications including senna, cascara, bisacodyl, and sodium picosulfate are commonly used as stimulants.^136,137 The onset of action of bisacodyl is 6–12 hours after oral administration and the onset of action of senna is usually 1–3 hours.

In randomized, placebo-controlled trials of sodium picosulfate and oral bisacodyl, it was reported that these agents increased the number of CSBMs per week, improved the stool consistency, and decreased the constipation-related symptoms.^132,138,139 A senna-fiber combination was more effective than lactulose in treating constipation in geriatric long-stay patients.^116,140 A meta-analysis found that stimulant laxatives provided superior efficacy for chronic idiopathic constipation (relative risk, 0.54; 95% confidence interval [CI], 0.42–0.69). The number needed to treat with stimulant laxatives was 3 (95% CI, 2.0–3.5).¹⁴¹ These agents are traditionally advocated for short-term use only, due to safety concerns with long-term use.

It has been reported that stimulant laxatives are associated with significant adverse events, including malabsorption, electrolyte disturbance, dose-dependent cramping, diarrhea, abuse, and development of melanosis coli.^33,142–144 Cathartic colon is seen in some chronic users of stimulant laxatives, but it is unclear whether this is related to their prolonged use.^145,146 Thus, stimulant laxatives may be used when patients fail to respond adequately to bulk or osmotic laxatives.^131,144

Docusate, a stool softener, acts as a surfactant, allowing water to penetrate the stool mass, and increases intestinal intraluminal water and sodium secretion. Although controversy has emerged regarding its effectiveness, docusate has been used to treat and prevent constipation in geriatric and institutionalized chronically ill patients.^147,148

Probiotics are defined as live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.¹⁴⁹ Previous studies have found that the intestinal microbiota in chronic constipation patients differed from that in healthy controls.^150,151 A systematic review of RCTs to evaluate the efficacy and safety of probiotic supplementation for the treatment of constipation suggested a favorable effect of treatment with Bifidobacterium lactis DN-173 010, Lactobacillus casei Shirota, and Escherichia coli Nissle 1917 on defecation frequency and stool consistency.¹⁵² However, to achieve the same health benefits seen in clinical trials, probiotics should be administered with specific strains, at a specific doses, in specific populations of people. Although the use of probiotics for the treatment of constipation may be beneficial, RCTs of probiotics in chronic constipation have potential limitations. Probiotics can be considered for use in conjunction with other drugs in the treatment of chronic constipation.¹³²

Prucalopride is a novel gastrointestinal prokinetic agent and acts as a high-affinity, highly selective 5-hydroxytryptamine type 4 agonist.¹³² Prucalopride accelerated gastrointestinal and colonic transit in constipation patients.¹⁵³ Prucalopride, 2 mg once-daily treatment over 12 weeks, was more efficacious than a placebo in improving stool frequency and stool consistency, decreasing the need for rescue medications, reducing the symptoms of constipation in Asian and non-Asian women, and was found to be safe and well-tolerated.^154–158 In addition, in elderly patients, prucalopride has beneficial effects on bowel movements and constipation-associated symptoms.¹⁵⁹ Satisfaction with bowel function was maintained for up to 18 months of treatment with prucalopride.¹⁶⁰ Recently, prucalopride was more efficacious than placebo in improving stool frequency and life quality in men with chronic constipation, and was found to be safe and well-tolerated.¹⁶¹

Prucalopride is recommended at 2 mg once daily, however the dose for the elderly (> 65 years) and patients with severe renal impairment (glomerular filtration rate < 30 mL/min/m²) and severe hepatic impairment (Child-Pugh class C) should start at 1 mg once daily. Headache, nausea, abdominal pain, and diarrhea lead to discontinuation of prucalopride treatment in ~5% of patients. Prucalopride is contraindicated in patients with hypersensitivity, renal impairment requiring dialysis, intestinal perforation or obstruction, and severe inflammatory conditions of the intestinal tract.¹³² Previous nonselective 5-hydroxytryptamine type 4 agonists (cisapride and tegaserod) have been associated with significant interactions with other receptors, leading to adverse cardiovascular events and resulting in the withdrawal of these drugs from the market.⁴² However, serious cardiac toxicity has not been reported in patients taking prucalopride. Thus, when bowel symptoms are refractory to simple laxatives, prucalopride should be considered in patients with chronic constipation. If treatment with prucalopride is not effective after 4 weeks, patients should be re-examined and the benefits of continuing treatment should be reconsidered.

Behavioral therapy – biofeedback therapy

Sugical treatment

There are no controlled trials of surgery for patients with chronic constipation. However, surgical treatment for chronic constipation may improve constipation in patients who fail to achieve satisfaction through medical therapy. The overall rate of success documented in 39 studies involving 1423 patients was 86% (39–100%).¹⁸⁹ Total colectomy and ileorectal anastomosis are the most common surgical procedures for refractory constipation, and sigmoid colectomy, subtotal colectomy with ceco-rectal anastomosis, and left hemicolectomy have been used.¹⁸⁹ Recently, laparoscopic colectomy has showed similar success rates to open surgery.¹⁹⁰

A medical history, physical and laboratory examinations, colonoscopy, and barium enema are needed to rule out secondary causes of constipation, such as endocrine and metabolic disorders, neurologic disorders, myogenic disorders, and medications. Barium defecography and ARM studies are also required to evaluate evacuation disorders. CTT is necessary to diagnose STC for the decision of surgical treatment in constipation patients. Surgical interventions are less effective in patients who have constipation with upper gastrointestinal dysmotility, and studies including gastric emptying scan and small bowel transit time may be required.¹⁹¹ Surgical treatment, such as colectomy, has a limited role as a treatment option for a highly selected group of patients with STC and without defecatory disorder who have failed all non-surgical interventions, and in whom symptoms are sufficiently severe to contemplate major surgery due to serious complications and poor functional outcomes.¹⁹²

Obstructed defecation syndrome is associated with abnormalities of the pelvic organs including rectocele, rectal prolapse, and rectoanal intussusception. Surgical treatment can be an option for patients who have failed to achieve satisfaction through medical therapy, including biofeedback therapy.

Repair of the rectocele, transanal or transvaginal region, may improve obstructive defecation symptoms.⁵² Although surgery seems to correct anatomical defects, many side effects may occur (in approximately 50% of cases), such as constipation, fecal incontinence, incomplete bowel emptying, and sexual dysfunction.¹⁹³ Surgical treatment for internal rectal prolapse is controversial and is only considered when conservative treatments fail to alleviate the patient’s symptoms.¹⁹⁴ Abdominal operations include techniques involving suspension of the prolapsed rectum with or without foreign materials, and sigmoid resection with or without rectopexy. A perineal approach and transabdominal repair (rectopexy and resection) can be used to treat rectal prolapse.¹⁹⁵ Perineal operations include rectosigmoidectomy, Delorme’s operation, mucosal plication (Gant-Miwa procedure), and anal encirclement (Thiersch’s operation).¹⁹⁶

The role of surgical treatment for rectal intussusception is controversial, and should be restricted to selected cases in which medical therapy has failed. Delorme’s transrectal excision is an alternative procedure, and (laparoscopic) resection rectopexy is a new procedure that shows better results according to some researchers.

Local treatment – enema and suppositories

An enema is a popular method of treatment for constipation and has been used for hundreds of years in a variety of forms, including water, soapsuds, phosphate, and sugar solutions. Despite this long history, there is only anecdotal evidence of its value in the management of chronic constipation. Routine use is typically discouraged but may be necessary. Whereas tap water enemas seem safe for more regular use, electrolyte imbalances are more common with phosphate enemas.

However, even in the absence of strong evidence for the efficacy of an enema, many clinicians and patients find them useful and effective, both for the treatment of acute and chronic constipation, and as a means of preparing or cleansing the distal colon for endoscopic or surgical procedures. By distending the rectum, all enemas stimulate the colon to contract and eliminate the stool. Enemas may be effective in a subset of patients with obstructed defecation, and in preventing fecal impaction when chronic constipation is not intractable to medical treatment, including biofeedback therapy.¹⁹⁷

Enemas can be effective, but their routine use is typically discouraged due to serious adverse events, such as metabolic derangement or perforation. Hypertonic sodium phosphate enemas may cause severe phosphate nephropathy, especially in the elderly with chronic renal failure. Phosphate enemas should be used with caution in patients with impaired renal function, pre-existing electrolyte imbalances, risk of electrolyte disturbance (hypocalcemia, hyperphosphatemia, or hypernatremia), and chronic inflammatory bowel disease.¹⁹⁸ The cause of perforation in patients who underwent enemas has been reported to be the device tip, related to localized weakness of the rectal wall and obstruction.¹⁹⁹ Because of their adverse irritating effects, resulting in rectal mucosa damage, soap enemas should be avoided.

Suppositories can help to initiate or facilitate rectal evacuation and have been used for many decades for chronic constipation in many forms, including the presumably inert but lubricating glycerin, and as stimulants, such as bisacodyl. Despite their inclusion in many ‘bowel protocols’ and personal testimonials of individuals, there is limited evidence to support their usefulness in the management of chronic constipation.

Other non-pharmacological treatment