Effects of Clozapine on the Gut: Cross-Sectional Study of Delayed Gastric Emptying and Small and Large Intestinal Dysmotility

Background Gastrointestinal hypomotility in people taking clozapine is common, poorly understood and potentially dangerous. It causes distress and sometimes sudden death, with greater associated morbidity than the better known adverse effect of clozapine, agranulocytosis. Neither the mechanism nor prevalence of clozapine-induced gastrointestinal hypomotility is well understood. Previous studies show clozapine impedes colon transit, likely owing to anticholinergic and anti-serotonergic properties. However, regional gastrointestinal transit times (including gastric and small bowel emptying) have not been quantified. Methods We used wireless motility capsules to measure gastric emptying and small and large bowel transit times in clozapine-treated individuals. We tested 17 clozapine-treated patients without any known gastrointestinal dysfunction, and compared data with matched normative transit times. Results Clozapine-treated participants had significant ‘slow gut’, with dysmotility in at least one region of the gastrointestinal tract evident in 82%, with 59% experiencing multi-regional dysmotility. Delayed gastric emptying was diagnosed in 41%, delayed small bowel transit in 71% and delayed colon transit in 50%. Only 18% of participants had normal studies. Hypomotility was not correlated with ethnicity, sex or duration of treatment. Subjective reporting of constipation had low sensitivity in predicting dysmotility. Delayed gastric emptying had been unrecognised clinically for all participants. Conclusion Clozapine is associated with significant multi-regional gastrointestinal dysfunction. This is relevant when considering the relationship between clozapine use and conditions such as gastroparesis, choking, aspiration pneumonia, constipation, ileus and intestinal pseudo-obstruction. While the constipating properties of clozapine are now well recognised, this study shows a high degree of vigilance is required for both lower and upper gastrointestinal dysmotility in people taking this antipsychotic.