Antipsychotic‐related Constipation

Antipsychotic‐related Constipation is a common and a potentially serious side-effect from antipsychotic use, but has received little attention in recent literature. It is particularly relevant in individuals on clozapine, but applies to anyone on antipsychotics. Unfortunately, antipsychotic-related constipation is not well researched, making general treatment recommendations dependent on expert opinion and limited studies.[1]

Constipation is very common in clozapine use and can affect up to 50% of patients.[2] It is critical for every patient on clozapine to have bowel monitoring for constipation. Clozapine has the potential to decrease GI motility, and is associated with risk of paralytic ileus, bowel obstruction, fecal impaction, bowel perforation, and in rare cases, death.[3] If other anticholingerics are also being used, then the prescribing clinician needs to be even more vigilant about bowel monitoring, since anticholingeric effects are additive. In addition, the risk of medication-related constipation also increases with age. Other conditions like diabetes mellitus can also further worsen constipation due to autonomic neuropathy.

Don't Forget About Constipation!

Constipation can be life-threatening. Severe constipation can cause bowel obstruction, sepsis and death. More deaths are caused by clozapine-induced ileus/megacolon than by agranulocytosis.[4]

Before Starting Clozapine

  • Obtain a baseline bowel movement history
  • Counsel patients on recognition and reporting of constipation.
  • Review all current medications and anticholinergic medications and stop other constipating medications wherever possible.
  • If baseline constipation exists, begin laxative treatment immediately.

Osmotic laxatives work by drawing fluid into the bowels to make stools looser.

Osmotic Laxatives

Name Strength Time of onset Tips
PEG (Lax-A-Day) Gentle Up to 48 hours required • Tolerance cannot develop
• Patients need to have adequate daily hydration
• Consider using regularly if patient has inconsistent BMs
Lactulose Strong 1-4 hours • Due to body's intolerance to lactulose, can cause significant gas and abdominal discomfort
• Strongly binds to ammonia in hepatic encephalopathy

Stimulant laxatives increases peristalsis in the bowels to help move stools.

Stimulant Laxatives

Name Strength Time of onset Tips
Sennosides Gentle 6-10 hours Tolerance can develop, and patients may require increased doses
Bisacodyl Strong 15 minutes-1 hour • Tolerance and dependence can develop
• Commonly used as bowel prep for colonoscopy

Constipation Management

1st line Osmostic agents:
• Polyethylene glycol (PEG): start 17 grams daily, and increase to 17 grams BID as needed (this is beyond manufacturers’ recommended dose).
• Lactulose: start 15-30 mL daily, and increase to 30 mL BID
Note: Combining lactulose and PEG 3350 combined is not a rational pharmacotherapy due to overlapping mechanisms.
2nd line Stimulant laxatives:
• Sennosides
• Bisacodyl
3rd line Fibre and bulk-forming products may be helpful, but can worsen constipation in underlying dehydration and should be used cautiously.
Adjunctive Dietary and exercise interventions should be considered as adjunct to laxative therapy as they are not likely to improve clozapine-induced constipation alone.
Not recommended There is no evidence for the use of surfactant agents (“stool softeners”) like docusate sodium for chronic constipation. These agents only lower the surface tension of stool, but are not effective at preventing and treating medication-induced constipation.[5]