Comparison of Laxative Agents for Constipation
Overview of Laxative Classes
Osmotic laxatives (polyethylene glycol) and stimulant laxatives (senna, bisacodyl) are the preferred first-line agents for treating constipation, while bulk-forming agents like psyllium have limited utility and stool softeners like docusate are ineffective. 1
Osmotic Laxatives (e.g., Polyethylene Glycol)
Mechanism of Action
- PEG works by sequestering fluid in the bowel, increasing water content in the large intestine through osmotic action 1, 2
- Lactulose is a semi-synthetic disaccharide that produces osmotic diarrhea and prevents ammonia-producing organism proliferation 1
- Magnesium salts draw fluid from the body into the bowel for rapid evacuation 1
Clinical Efficacy
- PEG has the strongest evidence (Grade A) supporting its use and offers excellent efficacy with a good safety profile 3
- PEG 17 g/day is particularly effective and well-tolerated in elderly patients 1
- Lactulose has moderate evidence (Grade B) and provides a prebiotic effect with a carry-over effect lasting 6-7 days post-cessation 4, 3
Safety Considerations
- Magnesium-containing laxatives must be avoided in renal impairment due to hypermagnesemia risk 1, 5
- PEG is the safest option in chronic kidney disease due to minimal systemic absorption 5
- Sodium salts should be avoided as they cause sodium and water retention 1
Stimulant Laxatives (e.g., Senna, Bisacodyl)
Mechanism of Action
- Stimulant laxatives increase intestinal motility by stimulating the myenteric plexus and inhibiting colonic water absorption 1
- Anthraquinone laxatives (senna) are converted to active sennosides in the colon, requiring sufficient intestinal motility for bacterial degradation 1
- Diphenylmethane derivatives (bisacodyl, sodium picosulfate) stimulate sensory nerves in the proximal colon and increase fluid movement into the colonic lumen 1
Clinical Efficacy
- Stimulant laxatives are generally preferred alongside osmotic agents as first-line therapy 1
- They are particularly useful when osmotic laxatives alone provide inadequate response 1
- For opioid-induced constipation specifically, osmotic or stimulant laxatives are the preferred options 1
Safety Considerations
- Generally safe in renal impairment as they work locally with minimal systemic absorption 5
- Should be avoided in intestinal obstruction 1
- Often cause abdominal cramping; excessive use can lead to diarrhea and hypokalemia 1
- Contrary to historical concerns, there is no clinical or animal evidence that prolonged sennoside use damages intestinal muscle or myenteric neurons 1
Bulk-Forming Agents (e.g., Psyllium)
Mechanism of Action
- Psyllium increases stool volume and weight, facilitating defecation through mechanical effects 6
- Works by absorbing water and expanding in the intestinal lumen 4
Clinical Efficacy
- Has moderate evidence (Grade B) for chronic constipation in general populations 3
- Increases stool frequency (3.8 vs 2.9 stools/week) and weight (665g vs 405g weekly) 6
- Improves stool consistency and reduces pain on defecation 6
- Does NOT accelerate colonic transit or change anorectal motor function—benefits are primarily related to facilitating the defecatory process 6
Critical Limitations
- Bulk laxatives like psyllium are NOT recommended for opioid-induced constipation 1
- Supplemental medicinal fiber is ineffective and may worsen constipation in cancer patients 1
- Requires adequate fluid intake to work effectively 1
- Should be used as first-line only in early-stage constipation with adequate dietary fiber and fluid 1
Stool Softeners (e.g., Docusate)
Mechanism of Action
- Docusate aids water penetration of the fecal mass by acting as a surfactant 1, 7
- Probably acts both as a mild stimulant and softening agent 1
Clinical Efficacy
- Docusate has NOT shown benefit in clinical trials and is NOT recommended 1
- Adding docusate to sennosides was LESS effective than sennosides alone in randomized controlled trials 1
- A study in hospice patients showed no benefit of adding docusate to sennosides compared with sennosides alone 1
Key Clinical Pitfall
- Despite widespread use, docusate lacks evidence of efficacy and should not be routinely prescribed 1
Clinical Algorithm for Selection
First-Line Approach
- Start with osmotic laxatives (PEG preferred) OR stimulant laxatives (senna, bisacodyl) 1
- Ensure adequate fluid intake and mobility within patient limits 1
Second-Line Approach
- If inadequate response to osmotic laxative alone, ADD a stimulant laxative 1
- Consider opioid rotation to fentanyl or methadone if opioid-induced 1
Special Populations
- Opioid-induced constipation: Use osmotic or stimulant laxatives; avoid bulk agents; consider peripheral opioid antagonists (methylnaltrexone, naloxegol, naldemedine) if refractory 1
- Renal impairment: PEG is safest; avoid magnesium salts and sodium phosphate preparations 5
- Elderly patients: PEG 17g/day offers excellent safety profile 1
- Fecal impaction on digital rectal exam: Suppositories and enemas are first-line, not oral laxatives 1
What NOT to Use
- Do NOT use docusate—it lacks efficacy 1
- Do NOT use bulk agents for opioid-induced constipation 1
- Do NOT use magnesium salts in renal impairment 1, 5
- Do NOT use sodium phosphate preparations in renal impairment 5
Common Pitfalls to Avoid
- Prescribing docusate based on tradition rather than evidence—multiple trials show no benefit 1
- Using bulk-forming agents in opioid-induced constipation—they are contraindicated and may worsen symptoms 1
- Failing to prescribe prophylactic laxatives when initiating opioids—constipation is nearly universal and tolerance does not develop 1
- Using magnesium-containing laxatives in patients with any degree of renal impairment—risk of dangerous hypermagnesemia 5
- Using enemas in neutropenic or thrombocytopenic patients—contraindicated due to infection and bleeding risk 1