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CNS Drugs
Published in: CNS Drugs 1/2017

01-01-2017 | Original Research Article

The Porirua Protocol in the Treatment of Clozapine-Induced Gastrointestinal Hypomotility and Constipation: A Pre- and Post-Treatment Study

Authors: Susanna Every-Palmer, Pete M. Ellis, Mike Nowitz, James Stanley, Eve Grant, Mark Huthwaite, Helen Dunn

Published in: CNS Drugs | Issue 1/2017

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Abstract

Background

Clozapine, an antipsychotic used in treatment-resistant schizophrenia, causes slow gastrointestinal transit in 50–80% of patients. Clozapine-induced gastrointestinal hypomotility is both common and serious, and potential complications include severe constipation, ileus, bowel obstruction and related complications, with a higher mortality rate than clozapine-related agranulocytosis. Little evidence exists on its prevention and management.

Method

Using a well-validated radiopaque marker (‘Metcalf’) method, we compared colonic transit times (CTTs) of clozapine-treated inpatients not receiving laxatives with their transit times when receiving laxatives, with treatment prescribed according to the Porirua Protocol for clozapine-related constipation (docusate and senna augmented by macrogol 3350 in treatment-resistant cases).

Results

The median age of participants was 35 years, and median clozapine dose, plasma level and duration of treatment were 575 mg/day, 506 ng/mL and 2.5 years, respectively. Overall, 14 participants (10 male) were enrolled and all completed the study. Transit times improved markedly with laxative treatment. Median colonic transit without laxatives was 110 h (95% confidence interval [CI] 76–144 h), over four times longer than normative values (p < 0.0001). Median CTT with laxatives was 62 h (95% CI 27–96 h), a 2-day reduction in average transit time (p = 0.009). The prevalence of gastrointestinal hypomotility decreased from 86% pre-treatment to 50% post-treatment (p = 0.061). Severe gastrointestinal hypomotility decreased from 64 to 21% (p = 0.031). Subjective reporting of constipation did not correlate well with objective hypomotility, and did not change significantly with treatment.

Conclusion

Treating clozapine-treated patients with docusate and senna augmented by macrogol appears effective in reducing CTTs in clozapine-induced constipation. Randomised controlled trials are the next step.
Australian New Zealand Clinical Trial Registry ACTRN12616001405404 (registered retrospectively).
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Metadata
Title
The Porirua Protocol in the Treatment of Clozapine-Induced Gastrointestinal Hypomotility and Constipation: A Pre- and Post-Treatment Study
Authors
Susanna Every-Palmer
Pete M. Ellis
Mike Nowitz
James Stanley
Eve Grant
Mark Huthwaite
Helen Dunn
Publication date
01-01-2017
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 1/2017
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-016-0391-y

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