Patients treated with the antipsychotic clozapine were found to have delayed colonic transit that was 4 times longer than normal, findings from a new study published in EBioMedicine reported.

Gastrointestinal (GI) side effects due to antipsychotics range from mild constipation to fatal bowel obstruction and/or ischemia. GI transit times in patients taking antipsychotics have not been measured in the past. Researchers from New Zealand used standardized radiopaque marker methods to determine colonic transit times of antipsychotic-treated inpatients and compared them to the population’s normative values. Data was analyzed by antipsychotic type, antipsychotic dose equivalent, anticholinergic load, duration of treatment, gender, ethnicity, and age. 

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The median colonic transit time was 23 hours for patients not prescribed clozapine vs. 104.5 hours in those taking clozapine—more than 4 times the normative values or in patients taking another antipsychotic (P<0.-0001). Also, 80% of clozapine-treated patients experienced gastrointestinal hypomotility vs. 0% of patients prescribed other antipsychotics (olanzapine, risperidone, paliperidone, aripiprazole, zuclopenthixol, or haloperidol). 

Researchers found abnormalities in right, left, and rectosigmoid motility suggesting pan-colonic pathology. Hypomotility was observed regardless of gender, age, ethnicity, or length of clozapine therapy. Colonic transit times were not positively correlated with duration of treatment, total antipsychotic load, or demographic factors. The study authors added that patient-reported constipation had low sensitivity in predicting hypomotility.

The study findings may help explain morbidity and mortality from GI complications (eg, bowel obstruction) related to clozapine therapy. In conclusion, researchers recommend a prophylactic laxative for all clozapine-treated patients.

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