Effects of Clozapine on the Gut: Cross-Sectional Study of Delayed Gastric Emptying and Small and Large Intestinal Dysmotility
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.
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.
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.
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.
The authors thank the Maurice and Phyllis Paykel Trust, Research for Life and Capital and Coast District Health Board for supporting clinical research; Roger Lentle and Ivana Sequeira for generously sharing equipment and expert knowledge; James Stanley, biostatistician, for advice on statistical methods; and the individuals who participated in this study.
SEP was the principal investigator. She conceived the study, designed and coordinated it, and had responsibility for drafting the study protocol and report; PE and SI contributed to the study design; EG recruited participants and collected data; and SI and SEP analysed the data. All authors approved the final version of the manuscript.
Compliance with Ethical Standards
This study was funded in full by grants from the Maurice and Phyllis Paykel Trust and the New Zealand Wellington Medical Research Foundation. The funders had no role in the study design; collection, analysis and interpretation of the data; or in writing or submitting the report for publication. The wireless motility capsule software was lent to the University of Otago by the Institute of Food, Nutrition and Human Health, Massey University, Palmerston North, New Zealand. The original purchase was enabled by a grant from the Ministry of Business Innovation and Employment (formerly Science and Innovation), New Zealand, contract number C06X0807.
Conflict of Interest
Susanna Every-Palmer, Stephen J. Inns, Eve Grant and Pete M. Ellis have no conflicts of interest that are directly relevant to the contents of this study. None of the authors have any relevant commercial or financial relationships that could be construed as a potential conflict of interest, nor received payment for presentations associated with this or with related studies.
The study was approved by the New Zealand Health and Disability Ethics Committee (reference (15/CEN/114)). All procedures were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Consent to Participate
All patients provided written informed consent.
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