Genetic factors contribute to medication-induced QT prolongation: A review

Abstract

QT prolongation is a heart rhythm condition that impacts the lives of many people and when severe can be life-threatening. QT prolongation has been linked to variations in several genes, but it can also arise in the course of treatments with medications such as certain antipsychotics and antidepressants. However, it is unclear whether the risk of medication-induced QT prolongation (MIQTP) depends on specific genetic vulnerability. Here, we review the available literature on the interplay between genetic risk and medication exposure in the context of psychiatric treatment. A review was conducted on the genetic contribution to MIQTP in psychiatric patients. A literature search was conducted on the PubMed platform with 8 papers meeting criteria for review. A total of 3,838 patients from 8 studies meeting criteria for a psychotic or mood disorder were included in this review. All studies found evidence for the genetic contribution to MIQTP. The specific genes identified in these studies included the NOS1AP, ABCB1, KCNH2, SLC22A23, EPB41L4A, LEP, CACNA1C, CERKL, SLCO3A1, BRUNOL4, NRG3, NUBPL, PALLD, NDRG4 and PLN genes. The findings highlight both the importance of monitoring heart parameters in psychiatry and the possible role for genetic profiling to increase the treatment safety.

Keywords: Antidepressants; Antipsychotics; Drug-induced QT prolongation; Pharmacogenetics.