Strategy for a genetic assessment of antipsychotic and antidepressant-related proarrhythmia.
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.
Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli, 5, 40123 Bologna BO, Italy.
Antonio
A
Drago
Fabrizio
F
De Ponti
Giuseppe
G
Boriani
Diana
D
De Ronchi
Alessandro
A
Serretti
D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000737:chemistry*; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000737:chemistry*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers; D004562:Electrocardiography; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D015415:Biomarkers; D007473:Ion Channels