Division of General Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, 1202 Geneva, Switzerland.
BMC Psychiatry. 2012 Dec 5;12:220. doi: 10.1186/1471-244X-12-220.
Numerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome (aLQTS). All of them are thought to act at the level of KCNH2, a subunit of the potassium channel. Although the QT-prolonging drugs are proscribed in the subjects with aLQTS, the individual response to diverse QT-prolonging drugs may vary substantially.
We report here a case of aLQTS in response to small doses of risperidone that was confirmed at three independent drug challenges in the absence of other QT-prolonging drugs. On the other hand, the patient did not respond with QT prolongation to some other antipsychotics. In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone, had no effect on QT-length. A detailed genetic analysis revealed no mutations or polymorphisms in KCNH2, KCNE1, KCNE2, SCN5A and KCNQ1 genes.
Our observation suggests that some patients may display a selective aLQTS to a single antipsychotic, without a potassium channel-related genetic substrate. Contrasting with the idea of a common target of the aLQTS-triggerring drugs, our data suggests existence of an alternative target protein, which unlike the KCNH2 would be drug-selective.
许多结构上不相关的药物，包括抗精神病药，可延长 QT 间期并引发获得性长 QT 综合征（aLQTS）。人们认为它们都作用于钾通道的 KCNH2 亚基。尽管 QT 延长药物在 aLQTS 患者中被禁止使用，但个体对不同 QT 延长药物的反应可能有很大差异。
我们在此报告一例因小剂量利培酮引起的 aLQTS，在没有其他 QT 延长药物的情况下，通过三次独立的药物挑战得到了证实。另一方面，该患者对其他一些抗精神病药没有出现 QT 延长反应。特别是，氯氮平（已知比利培酮更容易导致 QT 延长）的给药对 QT 长度没有影响。详细的基因分析显示 KCNH2、KCNE1、KCNE2、SCN5A 和 KCNQ1 基因没有突变或多态性。
我们的观察表明，一些患者可能对单一抗精神病药表现出选择性 aLQTS，而没有钾通道相关的遗传基础。与 aLQTS 触发药物的共同靶点的观点相反，我们的数据表明存在替代的靶蛋白，与 KCNH2 不同，它具有药物选择性。
