Strategy for a genetic assessment of antipsychotic and antidepressant-related proarrhythmia

Antonio Drago, Fabrizio De Ponti, Giuseppe Boriani, Diana De Ronchi, Alessandro Serretti

Research output: Contribution to journalArticle

Abstract

Antidepressants and antipsychotics may affect several ion channels involved in the control of cardiac action potential and be proarrhythmic. In this field, accurate understanding of genetics, which per se is a non-controllable risk factor, may help clinicians to prevent life-threatening side effects. So far, a number of genes have been associated with arrhythmia: SCN5A, SCN4B, CACNL1AC, KCNH2, KCNQ1, KCNE1, ANK2, ALG10, KCNJ2, KCNE2, RYR2, KCND3, KCND2, ACE, NOS1AP, CASQ2 and Rad. These genes represent good candidates for the definition of a genetic pro-arrhythmic profile. A genetic analysis of these targets is provided and their possible pathophysiological role in arrhythmias is discussed. Special attention is devoted to the interactions between these genes and new generation antidepressants and antipsychotics. A list of relevant rare mutations within the selected genes is presented, together with a complete list of Tag SNPs covering the whole genetic sequence. The aim of this paper is to define a part of the genetic framework responsible for the proarrhythmic effects of antidepressants and antipsychotics. The selected variants, both mutations and polymorphisms, may help in defining a next-to-come genetic assessment to be performed before drug prescription in order to improve drug safety.

Original languageEnglish
Pages (from-to)2472-2517
Number of pages46
JournalCurrent Medicinal Chemistry
Volume15
Issue number24
DOIs
Publication statusPublished - 2008

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Keywords

  • Adverse events
  • Antidepressants
  • Antipsychotics
  • Arrhythmia
  • Cardiotoxicity
  • Long QT
  • Pharmacogenetics

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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