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How To Prevent a Lethal Clozapine Side Effect

The Carlat Psychiatry Blog, Volume , Number ,

Gastric hypomotility is a common clozapine side effect that can develop into the potentially lethal condition of paralytic ileus. Dr. Aiken’s covered these risks in The Carlat Psychiatry Report. Here’s what you need to know.

Dangers of Paralytic Ileus:

  • Hypomotility is very common. Clozapine is the worst offender out of any other antipsychotics. 50% – 80% of clozapine patients experience hypomotility.
  • High fatality rate. Approximately, 1 in 1000 clozapine-treated patients die from bowel complications. This is 3-6 times higher than the death rate of clozapine-induced neutropenia. 
  • Anticholinergics increase the risk. Elderly patients on clozapine and anticholinergics are  6 times more likely to develop intestinal ileus. The FDA advises minimizing the use of other constipating medications as well as anticholinergics, including Cogentin and Benadryl, with clozapine.
  • Fiber supplements won’t help. When constipation is caused by hypomotility, fiber supplements and bulk-forming laxatives should be avoided. These treatments form a bulk that can block the intestines. 

Warning Patients: 

1. Educate patients about paralytic ileus and the symptoms of hypomotility prior to starting clozapine.

2. More aggressive treatment is needed if these constipation symptoms emerge:

  • Less than 3 bowel movements a week
  • Hard or dry stools
  • Difficulty passing gas

3. An urgent care evaluation is necessary when the previous symptoms are coupled with the more serious ones:

  • Moderate to severe abdominal pain lasting > 1 hour
  • Nausea, vomiting
  • Abdominal bloating or swelling
  • Bloody diarrhea

The Porirua Protocol:

1. Prevention. Start preventative treatment of docusate 100 mg qhs with senna 17.2 mg qhs along with a patient’s first clozapine prescription.

2. First Intervention. Increase preventative regimen to docusate 100 mg bid with senna 17.2 mg bid if the patient goes 48 hours without a bowel movement.

3. Second Intervention. After 4 days without a bowel movement, advise the patient to be evaluated by a primary care or urgent care provider to determine if enemas or disimpaction are needed. If disimpaction is required, then stop the senna and docusate treatment. If it is not required, then add MiraLAX 17 g bid.

4. Specialist Care. If constipation continues after these steps, then a primary care provider or gastroenterologist should take over the treatment.

To read the full article, subscribe to The Carlat Psychiatry Report here.


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