What is the best approach for managing constipation in a patient taking clozapine (Clozaril)?

Management of Clozapine-Induced Constipation

All patients starting clozapine should receive prophylactic laxatives from day one, as clozapine-induced gastrointestinal hypomotility is a potentially fatal complication that occurs in 50-80% of patients and has a higher mortality rate than clozapine-related agranulocytosis. 1, 2, 3

Prophylactic Strategy (Start Before Constipation Develops)

Initiate prophylactic treatment immediately when starting clozapine:

• Senna (stimulant laxative): 2 tablets twice daily 1
• OR Bisacodyl (stimulant laxative): 10-15 mg daily 1
• PLUS Polyethylene glycol (PEG): 17g (one heaping tablespoon) mixed in 8 oz water twice daily 1

Do NOT use docusate (stool softener) alone - it has no proven benefit and is ineffective as monotherapy for clozapine-induced constipation 1

Avoid fiber supplements or psyllium - these are contraindicated as they can worsen obstruction in patients with reduced gastrointestinal motility 1, 4

Monitoring Requirements

Screen for constipation before initiating clozapine and monitor frequently throughout treatment 2:

• Assess bowel movement frequency and character at every visit 2
• Critical warning: Subjective patient reports of constipation do NOT correlate well with objective gastrointestinal hypomotility - patients may have severe hypomotility without reporting symptoms 3
• Monitor for warning signs of complications: nausea, vomiting, abdominal distension, abdominal pain 2
• Consider abdominal examination and digital rectal exam if constipation is suspected 4

Treatment Algorithm for Established Constipation

Goal: Achieve one non-forced bowel movement every 1-2 days 4, 1

Step 1: Optimize First-Line Laxatives

• Increase bisacodyl to 10-15 mg two to three times daily 4, 1
• OR increase senna to 3 tablets twice to three times daily 4
• Ensure PEG is dosed at 17g twice daily 1
• Increase fluid intake significantly 4, 1
• Encourage physical activity within patient's limitations (even bed-to-chair transfers help) 4

Step 2: Add Alternative Osmotic Laxatives

If constipation persists after optimizing Step 1:

• Lactulose: 30-60 mL twice to four times daily 4
• OR Magnesium hydroxide: 30-60 mL once to twice daily 4
• Caution: Avoid magnesium-based laxatives in renal impairment due to hypermagnesemia risk 4

Step 3: Add Prokinetic Agent

For severe or refractory constipation:

• Metoclopramide: 10-20 mg orally four times daily 4
• This addresses the underlying hypomotility mechanism 4

Step 4: Consider Peripherally Acting Opioid Antagonist

For laxative-refractory cases:

• Methylnaltrexone: 0.15 mg/kg subcutaneously every other day (maximum once daily) 4, 1
• Note: This is typically used for opioid-induced constipation but may have benefit through blocking endogenous opioids 4

Management of Fecal Impaction

If digital rectal exam reveals fecal impaction, immediate intervention is required 4:

1. Glycerin suppository as first-line rectal intervention 4, 1
2. Bisacodyl suppository: 10 mg rectally once to twice daily 4, 1
3. Manual disimpaction: Premedicate with analgesic ± anxiolytic before performing digital fragmentation and extraction 4, 1
4. Tap water enema until clear if above measures fail 4

Contraindications to enemas: Recent colorectal/gynecological surgery, neutropenia, thrombocytopenia, paralytic ileus, bowel obstruction, recent pelvic radiation 4

Critical Pitfalls to Avoid

• Never delay prophylactic treatment - waiting for constipation to develop increases risk of life-threatening complications including bowel necrosis, perforation, and death 2, 5, 6
• Do not rely on patient-reported symptoms - 89% of patients with objective hypomotility may not report constipation 3
• Avoid anticholinergic medications when possible, as they worsen gastrointestinal hypomotility 2
• Rule out bowel obstruction with physical exam and consider abdominal x-ray if symptoms worsen despite treatment 4, 1
• Male patients may be undertreated - laxative use is more common in females (49%) than males (29%) despite similar clozapine exposure 7

When to Seek Emergency Evaluation

Immediately evaluate for surgical emergency if patient develops 2, 6:

• Severe abdominal pain
• Bilious or feculent vomiting
• Abdominal distension with absent bowel sounds
• Signs of peritonitis

These may indicate bowel obstruction, ischemia, necrosis, or perforation - complications that have resulted in multiple reported fatalities 5, 6

Supportive Measures

• Ensure privacy and proper positioning for defecation (small footstool may help) 4
• Abdominal massage may provide additional benefit, particularly in patients with neurogenic components 4
• Optimize toilet access, especially for patients with decreased mobility 4