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QTc interval prolongation and antipsychotic drug treatments: focus on sertindole

Lindstrom, E; Farde, L; Eberhard, Jonas LU and Haverkamp, W (2005) In International Journal of Neuropsychopharmacology 8(4). p.615-629
Abstract
Since the 1960s, physicians have been aware of electrocardiographic (ECG) abnormalities and cases of sudden death associated with the use of antipsychotic drugs in patients with schizophrenia. Explanations for Such deaths have traditionally focused on drug-induced prolongation of the QT interval leading to the development of life-threatening ventricular arrhythmias such as torsade de pointes (TdP). It is now apparent that most conventional and atypical antipsychotics can cause dose-related prolongation of the corrected QT interval (QTc), although there are important differences in the potency of individual agents. This review discusses potential mechanisms underlying QTc prolongation and arrhythinogenesis and examines the evidence for a... (More)
Since the 1960s, physicians have been aware of electrocardiographic (ECG) abnormalities and cases of sudden death associated with the use of antipsychotic drugs in patients with schizophrenia. Explanations for Such deaths have traditionally focused on drug-induced prolongation of the QT interval leading to the development of life-threatening ventricular arrhythmias such as torsade de pointes (TdP). It is now apparent that most conventional and atypical antipsychotics can cause dose-related prolongation of the corrected QT interval (QTc), although there are important differences in the potency of individual agents. This review discusses potential mechanisms underlying QTc prolongation and arrhythinogenesis and examines the evidence for a relationship between antipsychotic drugs and prolongation of the QTc interval. New electrophysiological and epidemiological data are presented which suggest there may not be a clear-cut cause-effect relationship between QTc prolongation and the development of ventricular tachyarrhythmias for all atypical antipsychotics. For at least one of these agents (sertindole), counterbalancing mechanisms may act to reduce the risk of proarrhythmic activity arising as a result of QTc prolongation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
sertindole, antipsychotic agents, QT interval, torsade de pointes
in
International Journal of Neuropsychopharmacology
volume
8
issue
4
pages
615 - 629
publisher
Cambridge University Press
external identifiers
  • pmid:15963244
  • wos:000233476700016
  • scopus:25844479293
ISSN
1469-5111
DOI
10.1017/S1461145705005250
language
English
LU publication?
yes
id
1d3b308f-f684-4abb-bca1-babd41dcf7bd (old id 212184)
date added to LUP
2007-08-23 08:54:29
date last changed
2017-08-07 14:33:15
@article{1d3b308f-f684-4abb-bca1-babd41dcf7bd,
  abstract     = {Since the 1960s, physicians have been aware of electrocardiographic (ECG) abnormalities and cases of sudden death associated with the use of antipsychotic drugs in patients with schizophrenia. Explanations for Such deaths have traditionally focused on drug-induced prolongation of the QT interval leading to the development of life-threatening ventricular arrhythmias such as torsade de pointes (TdP). It is now apparent that most conventional and atypical antipsychotics can cause dose-related prolongation of the corrected QT interval (QTc), although there are important differences in the potency of individual agents. This review discusses potential mechanisms underlying QTc prolongation and arrhythinogenesis and examines the evidence for a relationship between antipsychotic drugs and prolongation of the QTc interval. New electrophysiological and epidemiological data are presented which suggest there may not be a clear-cut cause-effect relationship between QTc prolongation and the development of ventricular tachyarrhythmias for all atypical antipsychotics. For at least one of these agents (sertindole), counterbalancing mechanisms may act to reduce the risk of proarrhythmic activity arising as a result of QTc prolongation.},
  author       = {Lindstrom, E and Farde, L and Eberhard, Jonas and Haverkamp, W},
  issn         = {1469-5111},
  keyword      = {sertindole,antipsychotic agents,QT interval,torsade de pointes},
  language     = {eng},
  number       = {4},
  pages        = {615--629},
  publisher    = {Cambridge University Press},
  series       = {International Journal of Neuropsychopharmacology},
  title        = {QTc interval prolongation and antipsychotic drug treatments: focus on sertindole},
  url          = {http://dx.doi.org/10.1017/S1461145705005250},
  volume       = {8},
  year         = {2005},
}