[Long QT Syndrome Induced by Antidepressants]

Area of Science:

• Pharmacology
• Cardiology
• Clinical Research

Background:

• Drug-induced long QT syndrome (LQTS) is diagnosed by QT interval prolongation (≥500 msec or ≥60 msec increase), increasing torsade de pointes (TdP) risk.
• Antipsychotic drugs are a frequent cause of drug-induced LQTS, with escitalopram also raising concerns.
• International guidelines (ICH E14) mandate QT prolongation studies for new drugs, with adapted regulations in Japan since 2010.

Purpose of the Study:

• To evaluate the QT prolongation effects of antidepressant and antipsychotic drugs available before 2010.
• To determine inter-drug differences and dose dependency in QT prolongation.
• To highlight the need for QT prolongation effect evaluation studies for older, still-used medications.

Main Methods:

• Review of existing data on QT prolongation effects of various drugs.
• Analysis of escitalopram's QT prolongation at different dosages.
• Comparison of QT prolongation effects between escitalopram and other antipsychotic drugs.

Main Results:

• Escitalopram showed a maximum 11.8 msec QT prolongation at 30 mg (overseas dosage), leading to contraindication in patients with prolonged QT.
• The approved Japanese dosage of escitalopram is 20 mg/day.
• Preliminary findings suggest some antipsychotic drugs may have greater QT prolongation effects than escitalopram.

Conclusions:

• Further QT prolongation effect evaluation studies are necessary for older antidepressant and antipsychotic drugs to understand inter-drug differences and dose dependency.
• Factors like female sex, hypokalemia, hypomagnesaemia, bradyarrhythmia, cardiac/CNS diseases, drug interactions, and gene mutations contribute to LQTS, complicating prediction.
• Close electrocardiogram monitoring is crucial in clinical practice for patients at risk of drug-induced long QT syndrome.