What are the best treatment options for a patient with chronic constipation?

Treatment of Chronic Constipation

Start with polyethylene glycol (PEG) as first-line pharmacological therapy after ruling out secondary causes, and if symptoms persist after 4-12 weeks, escalate to linaclotide 145 mcg or prucalopride 2 mg rather than continuing to increase laxative doses. 1, 2

Exclude Critical Secondary Causes First

Before initiating treatment, rule out reversible causes that can masquerade as chronic constipation:

• Check TSH to exclude hypothyroidism, a common and reversible cause 2
• Check serum calcium to exclude hypercalcemia, which presents with constipation, abdominal pain, and nausea 2
• Check basic metabolic panel for hypokalemia, which impairs colonic motility 2
• Screen for diabetes mellitus, which causes autonomic neuropathy affecting gut motility 2
• Review all medications systematically for constipating effects, including antacids, anticholinergics, antiemetics, and opioids 1, 2

First-Line Pharmacological Treatment

Polyethylene glycol (PEG) is the recommended first-line agent because it has moderate-quality evidence, is inexpensive, widely available, well-tolerated, and effective 1, 2:

• Dose: 17.5 g dissolved in 250 mL water twice daily 1
• Duration of trial: 4-12 weeks before escalating therapy 1, 2
• Common side effects: Abdominal distension, loose stool, flatulence, and nausea 1
• Response is durable over 6 months 1

Critical Pitfall: Discontinue Docusate Immediately

Stop docusate (stool softeners) immediately—it provides no therapeutic benefit and is less effective than stimulant laxatives alone. 2 One small study demonstrated that adding docusate to senna was unnecessary 1.

Alternative First-Line Options (If PEG Not Tolerated)

If PEG is not tolerated or available, consider these alternatives:

• Magnesium oxide: Start at lower dose and titrate upward; avoid in renal insufficiency due to hypermagnesemia risk 1
• Fiber supplementation (psyllium, wheat bran): Reasonable for mild constipation in patients with low dietary fiber intake, but evidence is low quality and studies are 30-40 years old 1
  • Take with 8-10 ounces of fluid 1
  • Chief side effect is flatulence 1
  • Avoid wheat bran if finely ground, as it can decrease stool water content and harden stool 1

Second-Line Pharmacological Treatment (After PEG Failure)

If symptoms do not respond adequately to PEG after 4-12 weeks, escalate to prescription agents rather than continuing to increase osmotic laxative doses. 1, 2

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 2:

• Mechanism: Guanylate cyclase-C agonist that increases intestinal fluid secretion and accelerates transit 3, 4
• Dosing: 145 mcg once daily on empty stomach, at least 30 minutes before first meal 3, 4
• Evidence: High-quality studies show improvements in CSBM frequency (approximately 1.5 CSBMs/week increase), stool consistency, and straining 4
• Side effects: Diarrhea (4.7% discontinuation rate) 3
• Contraindications: Known or suspected mechanical bowel obstruction, intestinal perforation 3

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 2, 3:

• Dosing: 2 mg once daily (reduce to 1 mg daily if creatinine clearance <30 mL/min) 3
• Side effects: Gastrointestinal adverse effects including diarrhea, typically transient and occurring in first week 3
• Contraindications: Mechanical bowel obstruction, intestinal perforation, Crohn's disease, ulcerative colitis, toxic megacolon/megarectum 3
• FDA caution: Monitor for unusual mood changes and suicidal ideation, though causality is unclear 3

Alternative Second-Line Option

Lubiprostone: Orally active prostaglandin analog that activates chloride channels to enhance intestinal fluid secretion 1, 5:

• Indication: FDA-approved for chronic idiopathic constipation in adults 5
• Use as replacement or adjunct to OTC agents 1
• Side effects: Nausea (dose-dependent; lower risk when taken with food and water) 1

Stimulant Laxatives: Short-Term or Rescue Therapy

Bisacodyl or sodium picosulfate are recommended for short-term use (≤4 weeks) or as rescue therapy in combination with other agents 1:

• Bisacodyl dose: 10-15 mg, 2-3 times daily with goal of 1 non-forced bowel movement every 1-2 days 1
• Common side effects: Abdominal pain, cramping, diarrhea 1
• Start at lower dose and increase as tolerated 1

Senna can also be used, though the dose evaluated in trials (higher than commonly used) should be started low and titrated 1.

Combination Therapy for Refractory Cases

If monotherapy with linaclotide or prucalopride provides insufficient relief after 4-12 weeks, consider adding the second agent 3:

• Initiate sequentially, not simultaneously, to minimize risk of excessive response and identify culprit if adverse effects occur 3
• Primary concern is diarrhea: If this occurs, reduce dose of one or both agents, temporarily hold one agent, ensure adequate hydration, and consider loperamide 4 mg initially, then 2 mg every 4 hours for severe cases 3

When to Perform Anorectal Testing

Perform anorectal manometry in patients who do not respond to first-line laxatives to identify defecatory disorders (dyssynergic defecation, pelvic floor dysfunction) 2. Biofeedback therapy is effective for dyssynergic defecation 1.

Red Flags Requiring Urgent Evaluation

Rule out mechanical bowel obstruction before escalating laxative therapy, particularly if there is:

• Left lower quadrant pain with nausea and severe constipation 2
• Fecal impaction requiring manual disimpaction or glycerin suppositories 1, 2

If impaction is present, administer glycerin suppositories or perform manual disimpaction 1.

Adjunctive Non-Pharmacological Measures

• Increase fluid intake in patients with low baseline fluid intake (those in lowest quartile for daily fluid intake are more likely to be constipated) 1
• Increase physical activity when appropriate 1
• Consider dietary fiber for patients with adequate fluid intake 1
• For Parkinson's disease patients: Fermented milk containing probiotics and prebiotic fiber in addition to increased water and fiber intake 1

Setting Realistic Expectations

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 2.