Gury C, Canceil O, Iaria P
Service de Pharmacie Clinique, CH Sainte-Anne, Paris.
Encephale. 2000 Nov-Dec;26(6):62-72.
Cardiovascular mortality is higher among schizophrenic patients than in the general population, and it is possible that most unexplained sudden deaths among these patients are due to ventricular arrhythmias for which antipsychotic drugs are either the cause or a predisposing factor. Most antipsychotic agents show electrophysiological effects resembling those of class 1a antiarrhythmic agents, and may be responsible for prolonging the QT interval, potentially going on to cause torsades de pointes. Some of the antipsychotic agents carry a high risk of arrhythmias, related to their effects on the QT interval. These include thioridazine, pimozide, sultopride, droperidol, and to a lesser extent haloperidol and chlorpromazine. In the case of the new atypical antipsychotic agents, it is possible to rank the risks of different drugs, with sertindole (now withdrawn from sale) having the highest risk, and ziprasidone somewhat lower, followed by risperidone and finally by quetiapine, clozapine and olanzapine which have negligible effects on the QT interval. A number of risk factors have been demonstrated, particularly: hypokalaemia and hypomagnesaemia, bradycardia, congenital long QT syndrome, and any underlying cardiac pathology. Lastly, the risk associated with any given antipsychotic agent is increased if it is combined either with any other drug known to prolong the QT interval and provoke torsades de pointes, or with any drug capable of inhibiting the hepatic metabolism of the antipsychotic agent. A list of such drugs is provided, together with advice on the action to be taken when prescribing an antipsychotic agent to a patient with a long QT interval.
精神分裂症患者的心血管死亡率高于普通人群，这些患者中大多数不明原因的猝死可能是由室性心律失常导致的，而抗精神病药物既是病因，也是诱发因素。大多数抗精神病药物表现出类似于1a类抗心律失常药物的电生理效应，可能会导致QT间期延长，进而可能引发尖端扭转型室性心动过速。一些抗精神病药物因对QT间期的影响而具有较高的心律失常风险。这些药物包括硫利达嗪、匹莫齐特、舒托必利、氟哌利多，以及程度较轻的氟哌啶醇和氯丙嗪。对于新型非典型抗精神病药物，可以对不同药物的风险进行排序，其中舍吲哚（现已退市）风险最高，齐拉西酮风险稍低，其次是利培酮，最后是对QT间期影响可忽略不计的喹硫平、氯氮平和奥氮平。已经证实了一些风险因素，特别是：低钾血症和低镁血症、心动过缓、先天性长QT综合征以及任何潜在的心脏病变。最后，如果某一特定抗精神病药物与任何其他已知可延长QT间期并引发尖端扭转型室性心动过速的药物联合使用，或者与任何能够抑制该抗精神病药物肝脏代谢的药物联合使用，那么其相关风险会增加。本文提供了此类药物的清单，以及在为QT间期延长的患者开具抗精神病药物时应采取的措施建议。
