Abstract
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 35years, and median clozapine dose, plasma level and duration of treatment were 575mg/day, 506ng/mL and 2.5years, 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 110h (95% confidence interval [CI] 76-144h), over four times longer than normative values (p<0.0001). Median CTT with laxatives was 62h (95% CI 27-96h), 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).
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