Clozapine induced gastrointestinal hypomotility: A potentially life threatening adverse event.

氯氮平（非典型抗精神病药）诱发胃肠动力不足：可能危及生命的不良事件（文献综述）

Abstract

OBJECTIVE:

The haematological and cardiac complications of clozapine have been well documented. Recent evidence from pharmacovigilance databases suggests that gastrointestinal (GI) complications are the leading cause of clozapine related deaths. This review aims to describe clinical features along with preventative and treatment options.

目的：目前已充分记录了氯氮平引起的血液并发症和心脏并发症。来自药物警戒数据库的最新证据表明，胃肠道（GI）并发症是与氯氮平相关死亡的主要原因。本综述旨在描述临床特征以及预防和治疗方案。

METHOD:

A review of MEDLINE via PubMed searching for all articles published up to February of 2016. Inclusion criteria were articles that provided clinical or epidemiological information relating to the diagnosis, outcome, management or pathophysiology of clozapine related gastrointestinal disorders in humans.

方法：通过PubMed检索MEDLINE，检索截至2016年2月发表的所有文章。纳入标准是提供与人氯氮平相关胃肠道疾病的诊断、结果、管理或病理生理学相关的临床或流行病学信息的文章。

RESULTS:

Three large case series were identified with 104 cases, 20 of these reported clinical details. A further 52 cases reports were included. Median age was 40, with 79% being male, mean daily clozapine dose was 453 mg. Mortality was 38% withsurvivors being younger (39 vs. 42), on lower daily doses (400 mg vs. 532 mg), more likely to be female (32% vs. 6%). Four patients were re-challenged with clozapine following CIGH, two suffered a recurrence.

结果：纳入了三个大型病例系列，含有104例，其中20例报告了临床细节。同时包括52个远期观察案例报告。中位年龄为40岁，其中79％为男性，平均每日氯氮平剂量为453mg。幸存者年龄较小（39：42），死亡率为38％，每日剂量较低（400mg：532mg），更可能是女性（32％：6％）。 4名患者在CIGH后再次接受氯氮平治疗，其中2名患者复发。

CONCLUSION:

Risk factors for CIGH appear to be older age, male gender, patients in the first four months of treatment, co-prescription of constipating agents, higher daily dose of clozapine, and previous CIGH. Risk factors for death were older age and male gender. Patients receiving clozapine should be counselled about the dangers of constipation and to report new GI symptoms. Once severe CIGH has occurred clozapine should be halted and reviewed with bowel symptoms managed promptly. Re-challenging with clozapine may present substantial risks due to the severity of CIGH and a paucity of evidence. From the available evidence a treatment strategy has been proposed. Further prospective data regarding CIGH are needed to allow a better assessment of the scale of the problem with the development and testing of treatment strategies.

结论：CIGH（题目缩写）的危险因素似乎是更大年龄、男性、处于接受治疗前四个月的患者，便秘药物的共同处方，氯氮平的日剂量较高以及之前患CIGH史。死亡的风险因素是年龄较大和男性。接受氯氮平治疗的患者应该咨询便秘的危险并报告新的胃肠道症状。一旦发生严重的CIGH，应立即停用氯氮平，并及时治疗肠道症状。由于CIGH的严重性和缺乏证据，再次应用氯氮平可能会带来很大的风险。根据现有证据，提出了治疗策略。目前需要有关CIGH的更多前瞻性数据，以便通过开发和测试治疗策略来更好进行临床评估。

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