Every-Palmer Susanna, Nowitz Mike, Stanley James, Grant Eve, Huthwaite Mark, Dunn Helen, Ellis Pete M
Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, New Zealand; Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New Zealand.
Department of Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New Zealand.
EBioMedicine. 2016 Feb 15;5:125-34. doi: 10.1016/j.ebiom.2016.02.020. eCollection 2016 Mar.
Gastrointestinal side effects are particularly common with clozapine and occur with other antipsychotics, ranging from mild constipation to fatal bowel obstruction and/or ischemia. While this adverse-effect spectrum has been attributed to 'gastrointestinal hypomotility', gastrointestinal transit times in antipsychotic-treated patients have not previously been measured, making this mechanism speculative.
Using standardized radiopaque marker ('Metcalf') methods we established colonic transit times of antipsychotic-treated psychiatric inpatients and compared them with population normative values. We analyzed results by antipsychotic type, antipsychotic dose equivalent, anticholinergic load, duration of treatment, gender, ethnicity, and age.
For patients not prescribed clozapine, median colonic transit time was 23 h. For patients prescribed clozapine, median transit time was 104.5 h, over four times longer than those on other antipsychotics or normative values (p < 0.0001). Eighty percent of clozapine-treated patients had colonic hypomotility, compared with none of those prescribed other antipsychotics (olanzapine, risperidone, paliperidone aripiprazole, zuclopenthixol or haloperidol). In the clozapine group, right colon, left colon and rectosigmoid transit times were all markedly abnormal suggesting pan-colonic pathology. Hypomotility occurred irrespective of gender, age, ethnicity, or length of clozapine treatment. Transit times were positively correlated with clozapine plasma level (rho = 0.451, p = 0.045), but not with duration of treatment, total antipsychotic load or demographic factors.
Clozapine, unlike the other antipsychotics examined, causes marked gastrointestinal hypomotility, as previously hypothesized. Pre-emptive laxative treatment is recommended when starting clozapine.
胃肠道副作用在使用氯氮平治疗时尤为常见，其他抗精神病药物也会出现此类副作用，范围从轻度便秘到致命性肠梗阻和/或缺血。虽然这种不良反应谱被归因于“胃肠动力不足”，但此前尚未测量抗精神病药物治疗患者的胃肠转运时间，因此这一机制只是推测。
我们采用标准化不透X线标志物（“梅特卡夫”）方法确定了接受抗精神病药物治疗的精神科住院患者的结肠转运时间，并将其与人群正常值进行比较。我们按抗精神病药物类型、等效抗精神病药物剂量、抗胆碱能负荷、治疗持续时间、性别、种族和年龄分析结果。
未服用氯氮平的患者，结肠转运时间中位数为23小时。服用氯氮平的患者，转运时间中位数为104.5小时，比服用其他抗精神病药物的患者或正常值长四倍多（p < 0.0001）。80%接受氯氮平治疗的患者存在结肠动力不足，而服用其他抗精神病药物（奥氮平、利培酮、帕利哌酮、阿立哌唑、珠氯噻醇或氟哌啶醇）的患者均无此情况。在氯氮平组中，右半结肠、左半结肠和直肠乙状结肠的转运时间均明显异常，提示全结肠病变。无论性别、年龄、种族或氯氮平治疗时长如何，均会出现动力不足。转运时间与氯氮平血浆水平呈正相关（rho = （此处原文可能有误，推测应为相关系数，假设为）0.451，p = 0.045），但与治疗持续时间、总抗精神病药物负荷或人口统计学因素无关。
与其他所研究的抗精神病药物不同，氯氮平如之前所假设的那样，会导致明显的胃肠动力不足。开始使用氯氮平时，建议预防性使用泻药治疗。
