Vieweg W VictorR
Departments of Psychiatry and Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Prim Care Companion J Clin Psychiatry. 2003 Oct;5(5):205-215. doi: 10.4088/pcc.v05n0504.
Recent regulatory and clinical concerns have brought into sharp focus antipsychotic drug-induced QTc interval prolongation, torsades de pointes, and sudden cardiac death. Several new generation (atypical) antipsychotic drugs have either been withdrawn from clinical use or delayed in reaching the marketplace due to these concerns. Because torsades de pointes is rarely found, QTc interval prolongation serves as a surrogate marker for this potentially life-threatening arrhythmia. Current methods of calculating this electrocardiographic parameter have limitations. The primary care physician is a key member of the team managing a patient who requires administration of antipsychotic drugs. This article focuses on new generation antipsychotic drugs and principles useful to both the primary care physician and the psychiatrist. METHOD: PubMed was searched in September 2002 using the terms antipsychotic drug and QT interval. References were examined from review articles describing antipsychotic drugs and the QT interval. The author's files gathered over the past 20 years on the QT interval were also reviewed. RESULTS: Nine cases were available in which drug-induced QTc interval prolongation was associated with new generation antipsychotic drug administration. Eight cases were taken from the literature, and the author added one additional report. The newer agents involved were risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. In one case frequently referenced in the literature, the authors misunderstood their own data showing that QTc interval prolongation did not relate to delayed ventricular repolarization. In another instance, 2 authors reported on the same patient, with important information missing from both articles. No evidence of torsades de pointes appeared in any of the 9 cases. CONCLUSIONS: No evidence is currently available in the literature implicating new generation antipsychotic drugs in the production of torsades de pointes. However, the absence of such evidence does not prove that newer antipsychotic drugs do not cause torsades de pointes. Among patients free of risk factors for QTc interval prolongation and torsades de pointes, current literature does not dictate any specific consultative or laboratory intervention before administering new generation antipsychotic drugs. When risk factors are present, evaluation and intervention specific to those risk factors should dictate the clinician's course of action. More specific guidelines for monitoring the QT interval and risk of torsades de pointes await improved methods of measuring the QTc interval relevant to each patient.
近期监管方面的关注以及临床问题使抗精神病药物引起的QTc间期延长、尖端扭转型室速和心源性猝死成为焦点。由于这些问题，几种新一代（非典型）抗精神病药物要么已退出临床使用，要么推迟上市。由于很少发现尖端扭转型室速，QTc间期延长作为这种潜在危及生命的心律失常的替代标志物。目前计算这一心电图参数的方法存在局限性。初级保健医生是管理需要使用抗精神病药物患者团队的关键成员。本文重点关注新一代抗精神病药物以及对初级保健医生和精神科医生都有用的原则。
2002年9月在PubMed上使用抗精神病药物和QT间期这两个术语进行搜索。从描述抗精神病药物和QT间期的综述文章中查阅参考文献。还查阅了作者在过去20年中收集的关于QT间期的文件。
有9例药物引起的QTc间期延长与使用新一代抗精神病药物有关。8例取自文献，作者补充了1例报告。涉及的新药有利培酮、喹硫平和齐拉西酮。至少8例中有证据表明存在与QTc间期延长相关的其他危险因素。在文献中经常引用的1例中，作者误解了他们自己的数据，表明QTc间期延长与心室复极延迟无关。在另一个例子中，2位作者报告了同一名患者，但两篇文章都缺少重要信息。9例中均未出现尖端扭转型室速的证据。
目前文献中没有证据表明新一代抗精神病药物会导致尖端扭转型室速。然而，缺乏此类证据并不能证明新一代抗精神病药物不会引起尖端扭转型室速。在没有QTc间期延长和尖端扭转型室速危险因素的患者中，目前的文献并未规定在使用新一代抗精神病药物之前进行任何特定的咨询或实验室干预。当存在危险因素时，针对这些危险因素的评估和干预应指导临床医生的行动。关于监测QT间期和尖端扭转型室速风险的更具体指南有待改进与每个患者相关的QTc间期测量方法。
