Electrophysiological and clinical fundamentals of QTc prolongation induced by antipsychotic medications

Abstract

Patients with psychiatric disorders undergoing antipsychotic treatment are at an elevated risk for adverse cardiovascular events, including arrhythmias and sudden cardiac death. While the precise mechanisms linking cardiovascular diseases and psychiatric conditions remain unclear, QTc prolongation is suspected to be a contributing factor. The human ether-à-go-go-related gene (hERG, or KCNH2), which affects potassium channels, is implicated in the cardiotoxicity of various medications, including antipsychotics. This gene plays a critical role in determining whether a drug will be approved for market use. This paper elucidates the electrophysiological basis of QTc prolongation and reviews the evidence concerning which antipsychotics may exacerbate QTc prolongation and which may offer a safer profile. Generally, second-generation antipsychotics, especially aripiprazole, exhibit a more favorable profile concerning QTc prolongation. Nonetheless, we advocate for further research, particularly into the newest antipsychotics, to establish more robust, evidence-based guidelines for psychiatrists.