• 作者：Susanna Every-Palmer^a ; ^b ; ^{susanna.every-palmer@ccdhb.org.nz" class="auth_mail" title="E-mail the corresponding author} ; Mike Nowitz^c ; James Stanley^d ; Eve Grant^a ; Mark Huthwaite^b ; Helen Dunn^e ; Pete M. Ellis^b
• 关键词：Antipsychotic agents ; Clozapine ; Gastrointestinal tract ; Laxatives ; Constipation ; Gastrointestinal motility
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：5
• 期：Complete
• 页码：125-134
• 全文大小：752 K

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This study confirms that the antipsychotic clozapine has profound effects on bowel function

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Median colonic transit time was 104.5 h if taking clozapine, > 4 times normative values or if on another antipsychotic

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Right, left and rectosigmoid motility were all significantly impaired suggesting pan-colonic pathology

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Colonic transit times were positively correlated with clozapine plasma level, but not other variables

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This is clozapine-specific: 80% of clozapine patients and 0% of those taking other antipsychotics had abnormal GI transit

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Findings may explain the clozapine-related morbidity and mortality from GI complications, such as bowel obstruction

For every thousand patients treated with clozapine, 300–600 will suffer constipation and at least four will develop serious gastrointestinal complications (including ileus, bowel obstruction, bowel ischaemia or necrosis), from which one will die. Iatrogenic mortality is higher from gastrointestinal complications than from agranulocytosis. However, the mechanism for these gastrointestinal complications has been poorly understood.

This study confirms clozapine has profound effects on bowel motility, with colonic transit in clozapine-treated patients taking four times longer than normal. 80% of clozapine patients had gastrointestinal hypomotility. Self-reported constipation had low sensitivity in predicting hypomotility. Prophylactic laxative treatment is recommended in all clozapine-treated patients.