QTc Interval Prolongation and Torsade de Pointes Associated with Second-Generation Antipsychotics and Antidepressants: A Comprehensive Review
- 29 August 2014
- journal article
- review article
- Published by Springer Science and Business Media LLC in CNS Drugs
- Vol. 28 (10), 887-920
- https://doi.org/10.1007/s40263-014-0196-9
Abstract
We comprehensively reviewed published literature to determine whether it supported the link between corrected QT (QTc) interval prolongation and torsade de pointes (TdP) for the 11 second-generation antipsychotics and seven second-generation antidepressants commonly implicated in these complications. Using PubMed and EMBASE, we identified four thorough QT studies (one each for iloperidone, ziprasidone, citalopram, and escitalopram), 40 studies specifically designed to assess QTc interval prolongation or TdP, 58 publications based on data from efficacy and safety trials, 18 toxicology studies, and 102 case reports. Thorough QT studies, QTc prolongation-specific studies, and studies based on efficacy and safety trials did not link drug-associated QTc interval prolongation with TdP. They only showed that the drugs reviewed caused varying degrees of QTc interval prolongation, and even that information was not clear and consistent enough to stratify individual drugs for this risk. The few toxicology studies provided valuable information but their findings are pertinent only to situations of drug overdose. Case reports were most informative about the drug-QTc interval prolongation-TdP link. At least one additional well established risk factor for QTc prolongation was present in 92.2 % of case reports. Of the 28 cases of TdP, six (21.4 %) experienced it with QTc interval <500 ms; 75 % of TdP cases occurred at therapeutic doses. There is little evidence that drug-associated QTc interval prolongation by itself is sufficient to predict TdP. Future research needs to improve its precision and broaden its scope to better understand the factors that facilitate or attenuate progression of drug-associated QTc interval prolongation to TdP.Keywords
This publication has 164 references indexed in Scilit:
- Methadone and Torsade de Pointes: How Can We Better Understand the Association?American Journal Of Medicine, 2013
- Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysisThe Lancet, 2013
- Low-dose escitalopram for 2 days associated with corrected QT interval prolongation in a middle-aged woman: a case report and literature reviewGeneral Hospital Psychiatry, 2012
- Dose dependent, new onset QTc prolongation in a patient with paranoid schizophrenia receiving ClozapineAsian Journal of Psychiatry, 2011
- Sudden cardiac death after treatment with low dose risperidone in combination with cotrimoxazoleAsian Journal of Psychiatry, 2011
- Acquired Long QT Interval: A Case Series of Multifactorial QT ProlongationClinical Cardiology, 2011
- Corrected QT interval prolongation after an overdose of escitalopram, morphine, oxycodone, zopiclone and benzodiazepinesCanadian Journal of Cardiology, 2008
- Electrocardiographic Effects of Fluoxetine and Doxepin in Patients With Major Depressive DisorderJournal of Clinical Psychopharmacology, 1997
- Fluoxetine and ventricular torsade — is there a link?International Journal of Cardiology, 1995
- Overdose of risperidoneAnnals of Emergency Medicine, 1993