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

2 Citations (Scopus)

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

Fingerprint

Antidepressive Agents
Antipsychotic Agents
Genes
Cardiac Arrhythmias
Drug Prescriptions
Ryanodine Receptor Calcium Release Channel
Mutation
Polymorphism
Ion Channels
Pharmaceutical Preparations
Action Potentials
Single Nucleotide Polymorphism
Safety

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Strategy for a genetic assessment of antipsychotic and antidepressant-related proarrhythmia. / Drago, Antonio; De Ponti, Fabrizio; Boriani, Giuseppe; De Ronchi, Diana; Serretti, Alessandro.

In: Current Medicinal Chemistry, Vol. 15, No. 24, 2008, p. 2472-2517.

Research output: Contribution to journalArticle

Drago, Antonio ; De Ponti, Fabrizio ; Boriani, Giuseppe ; De Ronchi, Diana ; Serretti, Alessandro. / Strategy for a genetic assessment of antipsychotic and antidepressant-related proarrhythmia. In: Current Medicinal Chemistry. 2008 ; Vol. 15, No. 24. pp. 2472-2517.
@article{24dd920651ba4fd981ca042bcfbc07e2,
title = "Strategy for a genetic assessment of antipsychotic and antidepressant-related proarrhythmia",
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.",
keywords = "Adverse events, Antidepressants, Antipsychotics, Arrhythmia, Cardiotoxicity, Long QT, Pharmacogenetics",
author = "Antonio Drago and {De Ponti}, Fabrizio and Giuseppe Boriani and {De Ronchi}, Diana and Alessandro Serretti",
year = "2008",
doi = "10.2174/092986708785909058",
language = "English",
volume = "15",
pages = "2472--2517",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "24",

}

TY - JOUR

T1 - Strategy for a genetic assessment of antipsychotic and antidepressant-related proarrhythmia

AU - Drago, Antonio

AU - De Ponti, Fabrizio

AU - Boriani, Giuseppe

AU - De Ronchi, Diana

AU - Serretti, Alessandro

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Adverse events

KW - Antidepressants

KW - Antipsychotics

KW - Arrhythmia

KW - Cardiotoxicity

KW - Long QT

KW - Pharmacogenetics

UR - http://www.scopus.com/inward/record.url?scp=55249115986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55249115986&partnerID=8YFLogxK

U2 - 10.2174/092986708785909058

DO - 10.2174/092986708785909058

M3 - Article

C2 - 18855674

AN - SCOPUS:55249115986

VL - 15

SP - 2472

EP - 2517

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 24

ER -