New Generation Antipsychotic Drugs and QTc Interval Prolongation

Abstract

Background: 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 Several new generation (atypical) antipsychotic drugs have either been withdrawn from clinical use or delayed in reaching the marketplace due to these concerns.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 druginduced 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.(Primary Care Companion J Clin Psychiatry 2003;5:205-215)

Sex difference in QTc prolongation in chronic institutionalized patients with schizophrenia on long-term treatment with typical and atypical antipsychotics

“…Furthermore, there are marked differences in QTc prolongation caused by different antipsychotic agents (Haddad and Anderson 2002). For example, typical antipsychotics are recognized as having a greater risk of QTc interval prolongation than are atypical antipsychotics (Vieweg 2003;Zemrak and Kenna 2008). Harrigan et al (2004) reported the effects of six antipsychotics on the QTc interval both in the absence and presence of metabolic inhibition using a prospective, randomized design.…”

A Psychiatric-Cardiac Case: Analysis for Education and Clinical Practice

“…Torsades de pointes is a rare but ominous precursor to ventricular tachycardia/fibrillation and cardiac arrest (Vieweg, 2003;Vieweg & Wood 2004) when a prolonged QT interval becomes longer than 500 ms. The QT interval represents the time from ventricular depolarization (QRS) through ventricular repolarization (T).…”

“…Normal intervals for QT in women are described by Vieweg (2003) as between 350-450 ms. An increased risk of developing Torsades occurs when the QT is longer than 500 ms. Dysrhythmia is identified as a medication side effect, but the mechanism underlying how antipsychotics and tricyclic antidepressants lead to dysrhythmias, such as Torsades, has not been fully understood.…”

Methadone, QTc interval prolongation and torsade de pointes: Case reports offer the best understanding of this problem

“…Rather than attempting to develop a database that can be analyzed using parametric statistics, we employed the principles of narrative medicine in a case report format as we have in our other papers assessing psychotropic drug-induced QTc interval prolongation and TdP [Vieweg, 2003;Vieweg et al 2004;Vieweg et al 2005;Vieweg et al 2009;Vieweg et al 2012]. Data from our review of case reports in the literature and analyses of those data form the body of our paper.…”