Clozapine Induced Constipation and Gastrointestinal Hypomotility (CIC & CIGH) – Case Report and Summary of Management Principles

Posted on:November 23, 2021
Last Updated: November 24, 2021
Time to read: 11–14 minutes

Constipation is a common side effect of clozapine and may cause death if severe. Unlike agranulocytosis and myocarditis, clozapine’s effects on bowel motility are both under-appreciated and under-recognised. The reported incidence of treatment-emergent constipation is 14% based on patients taking clozapine in clinical trials.[Novartis Clozaril package]

However, this may be an underestimate, with the prevalence of  Clozapine induced constipation (CIC) more likely to be 30–60%. [Attard et al., 2019]

Clozapine induced GI hypomotility (CIGH) is more prevalent and affects up to 73% of users; however, self-reporting is low. [Every-Palmer et al., 2020]

CIGH has a higher mortality rate than blood dyscrasias and is more common. Serious CIGH is a medical emergency.

A study that examined all reports of clozapine-induced severe gastrointestinal hypomotility (CIGH) submitted to the Australian Therapeutic Goods Administration, and New Zealand Pharmacovigilance Centre between 1992 and 2013 [A total of 43,132 people commenced clozapine] showed that: [Every-Palmer & Ellis, 2017]

  • 160 patients had serious gastrointestinal hypomotility with clozapine the suspected cause (37/10,000 clozapine users)
  • 66.3% were male
  • Few had received laxatives
  • At least 29 patients died (7/10,000 clozapine users), a reported case fatality rate of 18%

There was no consistent relationship between age, dose, or duration of treatment and the onset of life-threatening CIGH, making it hard to predict which clozapine-treated patients are most at risk of serious CIGH. [Every-Palmer & Ellis, 2017]

 

At the end of January 2020, the FDA issued a communications statement which [strengthened] an existing warning

That constipation caused by the schizophrenia medicine clozapine can, uncommonly, progress to serious bowel complications. [FDA ]

 

 

CIC can occur at any stage of clozapine administration. In contrast to agranulocytosis and myocarditis, where the risk is highest in the first 2 months, the risk for complications from constipation is high throughout the duration of clozapine treatment. [Rege & Lafferty, 2008]

Untreated constipation can lead to severe complications, including ileus, faecal impaction, colonic obstruction, toxic megacolon, bowel ischaemia and necrosis, perforation, and sepsis, all of which can be fatal.  The preva­lence of life‐threatening constipation with clozapine is 0.3%, and case fatality is as high as 28%. [Palmer et al., 2008]

Below is a summary of the key points in Clozapine Induced Constipation developed by Dr Pranav Mahajan: LOOSE STOOL [Original Poster]

References

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