What is the recommended step‑by‑step management of chronic constipation, including lifestyle modifications, first‑line osmotic laxatives (polyethylene glycol 3350), second‑line agents, use of stimulant laxatives, evaluation for secondary causes, and special considerations for an elderly patient with comorbidities?

Management of Chronic Constipation

Step 1: Initial Lifestyle Modifications

Begin with dietary modifications including increased fluid intake (particularly for patients in the lowest quartile of fluid consumption) and dietary fiber supplementation, combined with regular exercise and scheduled toileting after meals. 1

• For patients with mild-to-moderate constipation and fiber-deficient diets, trial fiber supplementation (14 g/1,000 kcal intake per day), though this receives only a conditional recommendation due to low-quality evidence 1
• Psyllium has the best evidence among fiber types, but all fiber data is 30-40 years old and of low quality 1
• Ensure adequate hydration (8-10 ounces of fluid with each fiber dose) as fiber intake increases to prevent worsening constipation 1
• Common side effects of fiber include bloating, flatulence, and abdominal discomfort 1

Critical pitfall: Wheat bran as finely ground powder can actually decrease stool water content and harden stool—avoid this formulation 1

Step 2: First-Line Pharmacological Therapy

If lifestyle modifications fail after a reasonable trial (typically 2-4 weeks), initiate polyethylene glycol (PEG) 3350 at 17 g daily as first-line pharmacological therapy. 1, 2

• PEG receives a strong recommendation with moderate-quality evidence from the 2023 AGA-ACG guidelines 1
• PEG demonstrates durable response over 6 months with sustained efficacy 1, 3
• Dose can be titrated based on symptom response with no clear maximum dose 1
• Side effects include abdominal distension, loose stool, flatulence, and nausea, but these are generally well-tolerated 1, 3
• PEG is inexpensive ($10-45/month), widely available, and cost-effective 1, 2

Continue PEG for 4-12 weeks before considering escalation to prescription agents. 2, 4

Step 3: Second-Line Prescription Agents

If PEG provides inadequate relief after 4-12 weeks of adequate trial, escalate to prescription secretagogues or prokinetic agents. 2, 4

Prescription Options (All with Strong Recommendations):

Linaclotide 72-145 mcg daily (intestinal secretagogue acting on guanylate cyclase-C receptors):

• Strong recommendation from 2023 AGA-ACG guidelines 1, 2
• May provide additional benefit for abdominal pain 1
• Can titrate up to 290 mcg daily based on response 1
• Cost approximately $523/month 1
• Diarrhea may occur in a subset of patients leading to discontinuation 1

Plecanatide 3 mg daily (similar mechanism to linaclotide):

• Strong recommendation as alternative secretagogue 1, 2, 4
• Cost approximately $526/month 1
• Also approved for IBS-C 1

Prucalopride 1-2 mg daily (serotonin type 4 agonist):

• Strong recommendation with different mechanism than osmotic/stimulant laxatives 1, 2, 4
• May provide additional benefit for abdominal pain 1
• Cost approximately $563/month 1
• Headaches and diarrhea may occur 1

Sodium picosulfate (stimulant laxative):

• Strong recommendation for short-term use (≤4 weeks) or rescue therapy 1, 2
• Can be combined with other agents 4

Step 4: Alternative and Conditional Agents

Conditional Recommendations (Lower Quality Evidence):

Lactulose 15 g daily (osmotic laxative):

• Conditional recommendation 1
• Only osmotic agent studied in pregnancy 1
• Bloating and flatulence may be limiting at higher doses 1
• Cost <$50/month 1
• PEG is superior to lactulose in stool frequency, stool form, and relief of abdominal pain 5

Magnesium oxide 400-500 mg daily (osmotic laxative):

• Conditional recommendation 1
• Critical contraindication: Do not use in patients with creatinine clearance <20 mL/min due to hypermagnesemia risk 4
• Prior studies used 1,000-1,500 mg daily 1

Senna 8.6-17.2 mg daily (stimulant laxative):

• Conditional recommendation with low-quality evidence 1, 2, 4
• Start low and titrate based on response 4
• Long-term safety and efficacy unknown 1

Bisacodyl 5-10 mg daily (stimulant laxative):

• Strong recommendation but only for short-term use or rescue therapy 1, 2, 4
• Recommended maximum 10 mg orally daily 1
• Prolonged or excessive use can cause diarrhea and electrolyte imbalance 1

Lubiprostone 24 mcg twice daily (chloride channel activator):

• Conditional recommendation 1
• May benefit abdominal pain 1
• Cost approximately $374/month 1

Step 5: Evaluation for Secondary Causes

Before escalating therapy, rule out secondary causes and red flags:

• Assess for fecal impaction or mechanical bowel obstruction, particularly with prominent fecal loading on imaging 2
• Evaluate for metabolic causes: hypercalcemia, hypokalemia, hypothyroidism, diabetes mellitus 1
• Review medication list and discontinue nonessential constipating medications (anticholinergics, antacids, opioids, antidepressants, antispasmodics, phenothiazines) 1
• Consider anorectal testing for defecatory disorders in patients not responding to over-the-counter agents 6
• Colonic transit studies may identify colonic dysmotility in refractory cases 6

Special Considerations for Elderly Patients with Comorbidities

Elderly patients require careful medication selection and monitoring:

• Renal impairment: Avoid magnesium-based laxatives (magnesium oxide, milk of magnesia, magnesium citrate) in patients with creatinine clearance <20 mL/min 1, 4
• Congestive heart failure: Sodium picosulfate/magnesium citrate is contraindicated 4
• Hyponatremia risk: Elderly patients (≥65 years) on sodium picosulfate have increased risk of hyponatremia (absolute risk increase 0.05%) 4
• Opioid-induced constipation: Consider peripherally acting μ-opioid receptor antagonists (methylnaltrexone 0.15 mg/kg every other day, naloxegol) to relieve constipation while maintaining analgesia 1
• PEG remains the safest first-line option in elderly patients with multiple comorbidities 2, 4

Critical Pitfalls to Avoid

Do not escalate osmotic laxative doses indefinitely—switch to prescription agents after 4-12 weeks if inadequate response. 2, 4

Do not continue current inadequate therapy without confirming at least 4 weeks of adequate trial. 2, 4

Do not prescribe magnesium-based products without checking renal function first. 4

Do not use stimulant laxatives (bisacodyl, senna, sodium picosulfate) as long-term monotherapy—reserve for short-term use (≤4 weeks) or rescue therapy. 1, 2, 4