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



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).



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.



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).
Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, Ratonga Rua-O-Porirua, Raiha Street, Porirua, PO Box 50-233, Wellington, New Zealand. susanna.every-palmer@ccdhb.org.nz.|Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington, 6242, New Zealand. susanna.every-palmer@ccdhb.org.nz.
Susanna
0000-0001-6455-9741
S
Every-Palmer
Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington, 6242, New Zealand.
Pete M
PM
Ellis
Department of Medicine, University of Otago, Wellington, PO Box 7343, Wellington, 6242, New Zealand.
Mike
M
Nowitz
Biostatistics Group, University of Otago, Wellington, PO Box 7343, Wellington, 6242, New Zealand.
James
J
Stanley
Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, Ratonga Rua-O-Porirua, Raiha Street, Porirua, PO Box 50-233, Wellington, New Zealand.
Eve
E
Grant
Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington, 6242, New Zealand.
Mark
M
Huthwaite
Pharmacy Department, Capital and Coast District Health Board, Private Bag 7902, Wellington South, New Zealand.
Helen
H
Dunn
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D054368:Laxatives / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy; D055815:Young Adult
D014150:Antipsychotic Agents; D054368:Laxatives; D003024:Clozapine