Department of Psychological Medicine, University of Otago, PO Box 7343, Wellington, 6242, New Zealand.
Department of Medicine (Gastroenterology), University of Otago, Wellington, New Zealand.
CNS Drugs. 2019 Jan;33(1):81-91. doi: 10.1007/s40263-018-0587-4.
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.
接受氯氮平治疗的人群常出现胃肠道动力不足，其发病机制和流行情况尚未完全阐明，且了解程度较差，可能具有潜在危险。这种动力不足会引起不适，有时甚至会导致突然死亡，其相关发病率高于氯氮平更为人所知的不良反应——粒细胞缺乏症。此前的研究表明，氯氮平可通过抗胆碱能和抗 5-羟色胺能作用来阻碍结肠转运，但对于氯氮平引起的胃肠道动力不足的机制和流行情况尚未完全了解。
我们使用无线动力胶囊来测量接受氯氮平治疗的个体的胃排空和小肠及大肠转运时间。我们测试了 17 名无任何已知胃肠道功能障碍的氯氮平治疗患者，并将数据与匹配的正常转运时间进行了比较。
氯氮平治疗患者的胃肠道明显“动力不足”，至少有一个胃肠道区域动力障碍的患者占 82%，多区域动力障碍的患者占 59%。诊断为胃排空延迟的患者占 41%，小肠转运延迟的患者占 71%，结肠转运延迟的患者占 50%。只有 18%的患者检查结果正常。动力不足与种族、性别或治疗时间无关。便秘的主观报告对动力障碍的预测敏感性较低。所有患者的胃排空延迟此前在临床上均未被识别。
氯氮平与明显的多区域胃肠道功能障碍有关。当考虑氯氮平使用与胃轻瘫、窒息、吸入性肺炎、便秘、肠梗阻和假性肠梗阻等疾病之间的关系时，这一点很重要。虽然氯氮平的致便秘作用现在已被广泛认识，但本研究表明，对于服用这种抗精神病药物的人群，需要高度警惕其下消化道和上消化道动力障碍。
