抗抑郁药引起的长QT综合征。

Yutaro Suzuki
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引用次数: 0

摘要

当经心率校正的QT间期(QTc)大于或等于500毫秒,或在开始、替代或增加药物剂量后延长60毫秒或更长时,可诊断为药物性长QT间期综合征,并认为在这些情况下发生严重室性心律失常的风险增加,称为扭转点(TdP)。长QT综合征分为先天性和继发性两大类,在被归为继发性的药物性长QT综合征中,除抗心律失常药物外,抗精神病药物被认为是TdP最常见的原因。与此同时,2011年上市的艾司西酞普兰因QT间期延长患者的给药禁忌症在日本引起了关注。国际人用药品注册技术要求协调会议(ICH) (E14)的指导方针要求对新药进行详细的QT间期延长效果评价研究(Thorough QT/QTc study),在日本,这已适用于2010年11月1日及之后申请的药物。研究结果显示,艾司西酞普兰给药剂量为30mg时比基线延长11.8毫秒,这是国外批准的剂量,因此成为QT延长患者的禁忌症;然而,由于艾司西酞普兰在日本的批准剂量为20mg /天,并且我们现场的研究表明,其他抗精神病药物可能比艾司西酞普兰具有更大的QT延长作用,因此我们的研究结果表明,有必要通过开展QT延长效果评估研究,确定2010年以前市售的抗抑郁药物和抗精神病药物的药物间差异和剂量依赖性。此外,延长QT间期的因素包括女性、低钾血症、低镁血症、慢速心律失常、各种心脏疾病、中枢神经系统疾病、药物相互作用和基因突变;其中,药物性长QT综合征的发生是由于这些因素的叠加和协同作用,使得QT延长难以预测。因此,在临床环境中需要仔细的心电图监测。
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[Long QT Syndrome Induced by Antidepressants].

A diagnosis of drug-induced long QT syndrome is made when the QT interval corrected for heart rate (QTc) is 500 msec or above or is prolonged 60 msec or more after initiating, substituting, or increasing the dose of the drug, and it is considered that the risk of severe ventricular arrhythmia, referred to as torsade de pointes (TdP), increases under these condi- tions. Long QT syndrome is divided into the two broad categories of congenital or secondary, and among drug-induced long QT syndrome, which is classified as secondary, antipsychotic drugs are considered to be the most frequent cause of TdP, excluding anti-arrhythmic drugs. At the same time, escitalopram, which became commercially available in 2011, garnered attention in Japan due to administration contraindication in patients with prolonged QT. The guidelines of the International Conference on Harmonization of Technical Requirements for Regis- tration of Pharmaceuticals for Human Use (ICH) (E14) requires a detailed QT prolongation effect evaluation study (Thorough QT/QTc study) for new drugs, and in Japan, this has been adapted to drugs applied for on and after Nov 1, 2010. As a result of the study, escitalopram demonstrated a maximum of 11.8 msec prolongation from baseline when administered at 30 mg, which is the approved dosage overseas, and thus became contraindicated in patients with prolonged QT ; however, since the approved dosage of escitalopram in Japan is 20 mg/day, and since the study at our site indicated that other antipsychotic drugs may have a QT prolongation effect greater than escitalopram, our findings suggest the necessity to determine inter- drug differences and dose dependency of the antidepressant drugs and antipsychotic drugs that were commercially available before 2010 and are still used today, by conducting QT prolongation effect evaluation studies. Furthermore, the factors prolonging the QT intervals include a female sex, hypokalemia, hypomagnesaemia, bradyarrhythmia, various cardiac diseases, central nerve system diseases, drug interactions, and gene mutations; wherein, drug-induced long QT syndrome occurs due to the additive and synergistic effects of these factors, making it difficult to predict QT prolongation. Therefore, careful electrocardiogram monitoring is required in clinical settings.

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