Treatment for Chronic Constipation
Start with polyethylene glycol (PEG) as first-line pharmacological therapy after discontinuing any constipating medications, and if symptoms persist after 4-12 weeks, escalate to secretagogues (linaclotide 145 mcg or lubiprostone) or the prokinetic prucalopride rather than continuing to increase laxative doses. 1
Initial Assessment and Medication Review
Before initiating any treatment, systematically review all medications for constipating effects including antacids, anticholinergics, and antiemetics, as these are reversible causes 2. Rule out secondary causes with targeted testing:
- Check TSH to exclude hypothyroidism, a common reversible cause 2
- Check serum calcium to exclude hypercalcemia, which presents with constipation, abdominal pain, and nausea 2
- Check basic metabolic panel to assess for hypokalemia, which impairs colonic motility 2
- Screen for diabetes mellitus, which can cause autonomic neuropathy affecting gut motility 2
First-Line Pharmacological Treatment
Osmotic laxatives, particularly polyethylene glycol (PEG), are the recommended first-line pharmacological agents because they are inexpensive, widely available, well-tolerated, and effective for chronic idiopathic constipation 1. The typical starting dose is PEG 17g once daily 3.
Immediately discontinue docusate if currently prescribed, as it provides no therapeutic benefit and has been shown to be less effective than stimulant laxatives alone 2, 3. The National Comprehensive Cancer Network and European Society for Medical Oncology do not recommend docusate due to lack of proven benefit and inadequate experimental evidence 3.
Stimulant laxatives (such as senna) can be used intermittently but are not recommended for long-term daily use as monotherapy 1. Fiber supplementation (20-25g daily) improves stool frequency and consistency but must be gradually adjusted over several days to avoid bloating and abdominal pain 4, 5.
Second-Line Pharmacological Treatment
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, 3, 6:
Secretagogues (Preferred for Constipation with Abdominal Pain/Bloating)
Linaclotide (Linzess) 145 mcg once daily is superior to osmotic laxatives for addressing both constipation and visceral pain 2, 7. It works by activating guanylate cyclase-C receptors, increasing intestinal fluid secretion and accelerating transit 6, 7. In clinical trials, 20% and 15% of patients achieved the primary endpoint (≥3 complete spontaneous bowel movements per week with an increase of ≥1 from baseline for at least 9 out of 12 weeks) compared to 3% and 6% with placebo 7.
Critical administration requirement: Linaclotide must be taken on an empty stomach at least 30 minutes before the first meal of the day, as taking it with food significantly reduces absorption and effectiveness 3, 6.
Lubiprostone 24 mcg twice daily is an alternative secretagogue that activates chloride channels 8. It is FDA-approved for chronic idiopathic constipation in adults 8.
Prokinetic Agent
Prucalopride (Motegrity) 2 mg once daily is a selective 5-HT4 receptor agonist that enhances colonic motility through high-amplitude propagated contractions 2, 6. It is particularly useful for severe motility dysfunction 2. Reduce to 1 mg daily if creatinine clearance is <30 mL/min 6.
Combination Therapy for Refractory Cases
If monotherapy with a secretagogue or prokinetic provides insufficient relief after an adequate 4-12 week trial, add the second agent sequentially (not simultaneously) to minimize risk of excessive response 6. The combination of linaclotide and prucalopride targets different mechanisms: secretion/transit acceleration and colonic motility enhancement 6.
If diarrhea occurs with combination therapy: reduce the 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 6.
Evaluation for Defecatory Disorders
Perform anorectal testing in patients who do not respond to first-line laxatives to identify defecatory disorders (dyssynergic defecation, pelvic floor dysfunction) 1, 5. These patients require biofeedback therapy rather than escalating laxatives, as biofeedback has been shown to improve rectoanal coordination and symptoms with high-quality evidence 1.
Red Flags Requiring Urgent Evaluation
Before escalating laxative therapy, rule out mechanical bowel obstruction, particularly if there is prominent fecal loading on imaging 2. The combination of left lower quadrant pain, nausea, and severe constipation warrants consideration of fecal impaction requiring manual disimpaction or glycerin suppositories 2.
Common Pitfalls to Avoid
- Do not continue docusate, as it has no proven therapeutic benefit 2, 3
- Do not start linaclotide with food, as this significantly reduces efficacy 3, 6
- Do not start with linaclotide 290 mcg for chronic idiopathic constipation, as this is the IBS-C dose and will cause excessive diarrhea; start with 145 mcg or 72 mcg in elderly/frail patients 3, 7
- Do not start combination therapy simultaneously in treatment-naive patients, as this increases risk of excessive response and makes it difficult to identify which agent is causing adverse effects 6
- Do not perform exhaustive testing before a therapeutic trial, as a trial of fiber supplementation and/or osmotic or stimulant laxatives is recommended before anorectal testing 1
Long-Term Management Expectations
Complete symptom resolution is often not achievable, and patients must understand that drug treatment is just one component of a multimodal approach 1. The efficacy of all drugs for constipation is modest, including newer agents specifically developed for this indication 1.