[Long QT Syndrome Induced by Antidepressants].

Abstract

A diagnosis of drug-induced long QT syndrome is made when the QT interval corrected for heart rate (QTc) is 500 msec or above or is prolonged 60 msec or more after initiating, substituting, or increasing the dose of the drug, and it is considered that the risk of severe ventricular arrhythmia, referred to as torsade de pointes (TdP), increases under these condi- tions. Long QT syndrome is divided into the two broad categories of congenital or secondary, and among drug-induced long QT syndrome, which is classified as secondary, antipsychotic drugs are considered to be the most frequent cause of TdP, excluding anti-arrhythmic drugs. At the same time, escitalopram, which became commercially available in 2011, garnered attention in Japan due to administration contraindication in patients with prolonged QT. The guidelines of the International Conference on Harmonization of Technical Requirements for Regis- tration of Pharmaceuticals for Human Use (ICH) (E14) requires a detailed QT prolongation effect evaluation study (Thorough QT/QTc study) for new drugs, and in Japan, this has been adapted to drugs applied for on and after Nov 1, 2010. As a result of the study, escitalopram demonstrated a maximum of 11.8 msec prolongation from baseline when administered at 30 mg, which is the approved dosage overseas, and thus became contraindicated in patients with prolonged QT ; however, since the approved dosage of escitalopram in Japan is 20 mg/day, and since the study at our site indicated that other antipsychotic drugs may have a QT prolongation effect greater than escitalopram, our findings suggest the necessity to determine inter- drug differences and dose dependency of the antidepressant drugs and antipsychotic drugs that were commercially available before 2010 and are still used today, by conducting QT prolongation effect evaluation studies. Furthermore, the factors prolonging the QT intervals include a female sex, hypokalemia, hypomagnesaemia, bradyarrhythmia, various cardiac diseases, central nerve system diseases, drug interactions, and gene mutations; wherein, drug-induced long QT syndrome occurs due to the additive and synergistic effects of these factors, making it difficult to predict QT prolongation. Therefore, careful electrocardiogram monitoring is required in clinical settings.