From the Guidelines
Constipation is a potentially life-threatening side effect when taking clozapine, and it requires immediate attention and preventive measures to avoid severe complications such as bowel obstruction, paralytic ileus, and bowel perforation. The most recent and highest quality study on managing adults with 22q11.2 deletion syndrome, published in 2023 in Genetics in Medicine 1, highlights the importance of monitoring and managing constipation in patients taking clozapine. Key points to consider in managing constipation in patients taking clozapine include:
- Maintaining adequate hydration (at least 2 liters of fluid daily)
- Consuming a high-fiber diet (25-30 grams daily)
- Exercising regularly
- Establishing a regular bathroom routine
- Using prophylactic stool softeners or mild laxatives like docusate sodium (100mg twice daily) or polyethylene glycol (17g daily) from the start of treatment
- Treating constipation promptly with osmotic laxatives, stimulant laxatives, or enemas as needed if it develops despite these measures
- Regularly monitoring bowel function in patients taking clozapine, as this side effect can develop at any time during treatment, even years after starting the medication. Other studies, such as the 2019 American Gastroenterological Association Institute guideline on the medical management of opioid-induced constipation 1 and the 2020 management of adult patients with severe chronic small intestinal dysmotility 1, provide additional guidance on managing constipation, but the 2023 study 1 is the most recent and relevant to the management of constipation in patients taking clozapine.
From the FDA Drug Label
Gastrointestinal Hypomotility with Severe Complications: Educate patients and caregivers on the risks, prevention and treatment of clozapine-induced constipation, including medications to avoid when possible (e.g., drugs with anticholinergic activity). Encourage appropriate hydration, physical activity, and fiber intake and emphasize that prompt attention and treatment to the development of constipation or other gastrointestinal symptoms is critical in preventing severe complications.
Constipation is dangerous when taking clozapine because it can lead to severe complications if not properly managed. These complications can arise due to gastrointestinal hypomotility, a condition where the movement of food through the digestive system slows down. It is crucial for patients and caregivers to be aware of the risks and take preventive measures, such as:
- Avoiding medications with anticholinergic activity
- Encouraging hydration, physical activity, and fiber intake
- Seeking prompt attention and treatment for constipation or other gastrointestinal symptoms to prevent severe complications 2.
From the Research
Constipation and Clozapine
- Constipation is a common side effect of clozapine, but it can be dangerous and even life-threatening in some cases 3, 4, 5, 6.
- The mechanism of clozapine-induced constipation is likely to be anticholinergic and antiserotonergic, affecting the entire gastrointestinal system 3.
- Constipation can lead to severe complications such as bowel obstruction, ischemia, perforation, and aspiration, with a mortality rate of 27.5% in one study 3.
Risk Factors and Prevention
- Probable risk factors for life-threatening constipation include recent instigation of clozapine, high clozapine dose or serum level, concomitant anticholinergic use, or intercurrent illness 3.
- Preventive measures such as high-fiber diet, adequate fluid intake, stool softeners, and exercise can help prevent constipation 4.
- Regular physical monitoring, appropriate and timely use of laxatives, and early referral of constipated patients are essential to prevent life-threatening complications 3.
Diagnostic Accuracy of Constipation Screening
- Self-reported constipation has low sensitivity in diagnosing clozapine-induced gastrointestinal hypomotility (CIGH), with only 26% of participants reporting constipation despite 73% having objective CIGH on motility testing 7.
- The Rome criteria improve sensitivity to 50%, but half the cases are still missed, making it no more accurate than tossing a coin 7.
- Prophylactic laxatives are suggested for people taking clozapine to prevent CIGH, as universal bowel motility studies are impractical 7.