What is the initial approach to treating an adult patient with chronic constipation and no significant past medical history?

Initial Approach to Chronic Constipation in Adults

Start with polyethylene glycol (PEG) as first-line pharmacological therapy after ruling out secondary causes and discontinuing constipating medications; if symptoms persist after 4-12 weeks, escalate to prescription secretagogues (linaclotide 145 mcg or lubiprostone 24 mcg) or the prokinetic prucalopride rather than continuing to increase laxative doses. 1

Exclude Critical Secondary Causes First

Before initiating treatment, systematically rule out reversible causes through targeted testing:

• Check TSH to exclude hypothyroidism, a common reversible cause 1
• Check serum calcium to rule out hypercalcemia, which presents with constipation, abdominal pain, and nausea 1
• Check basic metabolic panel for hypokalemia, which impairs colonic motility 1
• Screen for diabetes mellitus, which causes autonomic neuropathy affecting gut motility 1

Medication Review is Essential

• Systematically review all medications for constipating effects, including antacids, anticholinergic drugs, antiemetics, and opioids 1
• Discontinue docusate immediately if prescribed—it provides no therapeutic benefit and is less effective than stimulant laxatives alone 1

First-Line Pharmacological Treatment

• Initiate PEG (polyethylene glycol) as the first-line agent because it is inexpensive, widely available, well-tolerated, and effective for chronic idiopathic constipation 1
• PEG draws water into the intestine to hydrate and soften stool without directly stimulating the bowel 2
• Administer with food and water to improve tolerability 3

Second-Line Treatment (After 4-12 Weeks of PEG Failure)

If symptoms do not respond adequately to PEG after 4-12 weeks, escalate to prescription agents rather than increasing osmotic laxative doses 1:

For Constipation with Significant Abdominal Pain/Bloating:

• Linaclotide (Linzess) 145 mcg once daily is superior to osmotic laxatives for addressing both constipation and visceral pain 1, 4
• Linaclotide acts on guanylate cyclase-C receptors to stimulate chloride secretion, increasing luminal fluid and accelerating intestinal transit 2
• It also has visceral analgesic properties 2

For Severe Motility Dysfunction:

• Prucalopride (Motegrity) 2 mg once daily is a selective 5-HT4 receptor agonist that enhances colonic motility through high-amplitude propagated contractions 1
• Headache and gastrointestinal symptoms (abdominal pain, nausea, diarrhea) are the most frequent side effects but are usually transient 2

Alternative Second-Line Option:

• Lubiprostone 24 mcg twice daily for chronic idiopathic constipation 3
• Take with food and water; swallow capsules whole 3
• Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 3

When to Refer for Specialized Testing

• Perform anorectal testing in patients who do not respond to first-line laxatives to identify defecatory disorders (dyssynergic defecation, pelvic floor dysfunction) 1
• Biofeedback therapy improves symptoms in more than 70% of cases of defecatory disorders 5

Critical Red Flags Requiring Urgent Evaluation

• Rule out mechanical bowel obstruction before escalating laxative therapy, particularly with prominent fecal loading on imaging 1
• The combination of left lower quadrant pain, nausea, and severe constipation warrants consideration of fecal impaction requiring manual disimpaction or glycerin suppositories 1
• Patients with alarm symptoms (blood in stool, unintentional weight loss) or those overdue for colorectal cancer screening should be referred for colonoscopy 6

Important Caveats

• Complete symptom resolution is often not achievable, and patients must understand that drug treatment is just one component of a multimodal approach, with the efficacy of all drugs for constipation being modest 1
• Avoid stimulant laxatives as first-line therapy, though they can be added if osmotic laxatives provide inadequate response 1, 2
• Despite widespread concern, there is little evidence that routine use of stimulant laxatives is harmful to the colon 2