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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Oct 19, 2021; 11(10): 736-753
Published online Oct 19, 2021. doi: 10.5498/wjp.v11.i10.736
Antipsychotics cardiotoxicity: What's known and what's next
Xiao-Qing Li, Xin-Ru Tang, Li-Liang Li
Xiao-Qing Li, Xin-Ru Tang, Li-Liang Li, Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Author contributions: All authors participated sufficiently in the work to take public responsibility for its content; Li XQ and Tang XR drafted the paper; Li LL conceived the original idea, and drafted and edited the manuscript; all authors provided final approval of the version that was submitted; Li XQ and Tang XR had equal contributions and should be considered as co-first authors.
Supported by National Natural Science Foundation of China, No. 82070285 and No. 81701861.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Liang Li, MD, PhD, Associate Professor, Teacher, Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, No. 131 Dongan Road, Shanghai 200032, China. liliangli11@fudan.edu.cn
Received: February 24, 2021
Peer-review started: February 24, 2021
First decision: July 4, 2021
Revised: July 8, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: October 19, 2021
Processing time: 233 Days and 6.6 Hours
Abstract

Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns. These cardiotoxic effects range from arrhythmia to heart failure in the clinic, with myocarditis/cardiomyopathy, ischemic injuries, and unexplained cardiac lesions as the pathological bases. Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity. This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level. We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity. We propose that third-generation antipsychotics or drug adjuvant therapy, such as cannabinoid receptor modulators that confer dual benefits — i.e., alleviating cardiotoxicity and improving metabolic disorders — deserve further clinical evaluation and marketing.

Keywords: Antipsychotics; Cardiotoxicity; Sudden cardiac deaths; Cannabinoid receptor; Adrenoceptor

Core Tip: Antipsychotic drug-induced cardiotoxicity is troubling and sometimes life-threatening, which restricts their clinical application. Herein, we summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level. Future perspectives regarding clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity are also discussed.