Pharmacy Department, York Teaching Hospital NHS Foundation Trust, Wigginton Road, York, YO31 8HE, UK.
Eur J Clin Pharmacol. 2013 Apr;69(4):755-60. doi: 10.1007/s00228-012-1408-1. Epub 2012 Sep 21.
Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely used in clinical practice. Recent data have indicated that high therapeutic citalopram doses may cause electrocardiographic abnormalities, and the regulatory authorities have amended its licenced dosage. The present manuscript reviews the available data concerning citalopram and cardiac toxicity.
Published data concerning the cardiac effects of citalopram were ascertained, and clinical data were considered separately between adverse effects arising from therapeutic use versus toxicity in the setting of intentional overdose.
The occurrence of electrocardiographic abnormalities has long been recognised as a complication of acute citalopram overdose; a dose-effect relationship for QT prolongation has been described in a number of large case series, including several cases of torsades de pointes. In contrast, few data indicate the occurrence of QT prolongation and arrhythmia after therapeutic doses, and a dose-effect relationship within the therapeutic range has only recently been established. Citalopram is more likely to cause QT prolongation in patients with metabolic disturbance or pre-existing cardiac disease.
A dose-effect relationship for QT prolongation exists across a broad range of citalopram doses, such that caution must be exercised when prescribing high doses or if there are co-existent risk factors for QT effects. The available data illustrate how clinical toxicity data may offer an earlier signal of cardiac effects than ascertained from conventional pharmacovigilance methods.
西酞普兰是一种选择性 5-羟色胺再摄取抑制剂(SSRI)抗抑郁药,在临床实践中广泛应用。最近的数据表明,高治疗剂量的西酞普兰可能会引起心电图异常,监管部门已修改其许可剂量。本文综述了有关西酞普兰和心脏毒性的现有数据。
确定了有关西酞普兰心脏作用的已发表数据,并分别考虑了治疗用途和故意过量用药毒性所致不良反应的临床数据。
心电图异常的发生早已被认为是急性西酞普兰过量的并发症;许多大型病例系列研究描述了 QT 延长的剂量-效应关系,包括几例尖端扭转型室性心动过速。相比之下,很少有数据表明治疗剂量后会出现 QT 延长和心律失常,并且在治疗范围内的剂量-效应关系最近才得到证实。西酞普兰在代谢紊乱或存在潜在心脏疾病的患者中更有可能引起 QT 延长。
在广泛的西酞普兰剂量范围内存在 QT 延长的剂量-效应关系,因此在开具高剂量处方或存在 QT 效应的共存危险因素时必须谨慎。现有数据说明了临床毒性数据如何比常规药物警戒方法更早地提示心脏作用。