Clinical Context

Chronic idiopathic constipation (CIC) is a lower gastrointestinal tract disorder with symptoms including infrequent, incomplete defecation without mucosal or structural abnormalities. Medical costs of CIC management are estimated at approximately $2,000 to $7,500/patient/year. Effects on quality of life may be similar to those of chronic obstructive pulmonary disease, diabetes, and depression.

The first step in management is often nonpharmacological interventions, including dietary (increased fluid intake and fiber) and behavioral changes (exercise). Pharmacological treatment may include polyethylene glycol, secretagogues, and prokinetic agents.

Study Synopsis and Perspective

A new practice guideline aims to help clinicians navigate an increasingly crowded field of over-the-counter (OTC) and prescription treatment options for CIC in otherwise-healthy people.

The guideline, published in the American Journal of Gastroenterology, was developed jointly by the American Gastroenterological Association (AGA) and the American College of Gastroenterology. It marks the AGA’s first update on CIC, also called functional constipation, in a decade.

In an interview, guideline lead author Lin Chang, MD, from the University of California, Los Angeles, noted that CIC, defined as constipation lasting at least 3 months in the absence of malignancy or obstruction, a medication adverse effect, or inflammatory bowel disease, is common, affecting between 8% and 12% of all US adults. Most will be treated by primary care physicians, not specialists, Dr Chang said. And most will see their physicians having already tried different OTC treatments.

“The criteria for CIC or functional constipation, hasn’t really changed” since the last AGA guideline on it was published in 2013, Dr Chang said, adding that the diagnostic standard currently used is the Rome IV criteria for functional constipation. “There are just more medications right now than there were 10 years ago.”

The new guideline, into which evidence from 28 studies was integrated, offers recommendations regarding different types of fiber; the osmotic laxatives polyethylene glycol, magnesium oxide (MgO), and lactulose; and the stimulant laxatives bisacodyl, sodium picosulfate, and senna. It also assesses the secretagogues lubiprostone, linaclotide, and plecanatide and the serotonin type 4 agonist prucalopride.

One commonly used agent in clinical practice, the stool softener docusate sodium, does not appear in the guideline, as there were too few data available on it to make an assessment, Dr Chang said. Fruit-based laxatives were excluded because they were the subject of a recent evidence review. Lifestyle modifications such as exercise, surgical interventions, and probiotics were not assessed.

The guideline’s strongest recommendations are for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride, with conditional recommendations for fiber, lactulose, senna, MgO, and lubiprostone.

As monthly costs of the recommended therapies vary from less than $10 to more than $500, the authors also included price information, noting that “patient values, costs, and health equity considerations” must be factored into treatment choices. “For polyethylene glycol there’s a strong recommendation, although the certainty of evidence was moderate,” Dr Chang said. “And with fiber, even though we made only a conditional recommendation based on the evidence, our remarks and our algorithm make clear that it should be considered as a first-line treatment.”

In general, “if someone has more mild symptoms, you should try fiber or increase their fiber intake in their diet,” Dr Chang commented. “If that doesn’t work, try [OTC] remedies like polyethylene glycol. Then if symptoms are more severe, or if they fail the first-line treatments, then you go to prescription agents.”

In clinical practice, “there always considerations besides scientific evidence of safety and efficacy,” Dr Chang stressed. “You have to personalize treatment for the patient.” A patient may present having already failed with fiber, or who does not want to use magnesium or can’t afford a costlier agent.

The guidelines contain implementation advice that might guide choice of therapy or dosing. With the prescription osmotic laxative lactulose, for example, “you may not wish to use it as a first-line treatment because bloating and flatulence are very common,” Dr Chang said. “Our implementation advice makes that clear.” For senna, a stimulant laxative derived from the leaves of the senna plant and for which quality evidence is limited, the guideline authors stressed that patients should be started on low doses to avoid cramping.

Dr Chang said that although the new guideline covers medication options for otherwise-healthy adults, clinicians should be mindful that patients presenting with CIC might still have a defecatory disorder. “A person could also have pelvic floor dysfunction as a primary cause or contributing factor. If someone fails fiber or polyethylene glycol, consider a digital rectal examination as part of the physical exam. If this is abnormal, consider referring them for anorectal manometry.”

Untreated constipation carries risks, Dr Chang noted, but “sometimes people with bothersome symptoms don’t treat them because they’re worried they’ll become dependent on treatment. It’s a dependency in the sense that you have to treat any chronic condition, such as high blood pressure or diabetes, but the treatments aren’t addictive, except for some stimulant laxatives to which people can develop tolerance.”

Hemorrhoids and defecatory disorders can occur over time because of straining, Dr Chang said. “The pelvic wall can also get very lax, and that is hard to fix. Or, one can develop a rectal prolapse. Another thing that happens when people have longstanding constipation for many years is they start losing the urge to have a bowel movement.”

The guideline’s development was funded by the AGA and American College of Gastroenterology without industry support. Authors with conflicts of interest regarding a specific intervention or drug were not allowed to weigh in on those interventions.

Am J Gastroenterol. 2023;118(6):936-954.^[1]

Clinical Implications

• Recommendations were strong for use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride.
• Recommendations were conditional for use of fiber supplements, lactulose, senna, MgO, and lubiprostone, but fiber should be considered in first-line management.
• Implications for the Health Care Team: Nonpharmacological therapies are often initial management steps, including diet (better hydration; increased dietary fiber) and behavioral changes (exercise).

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