Cardiovascular side-effects of antipsychotic drugs: The role of the autonomic nervous system

Leung, Joanne Y.T.; Barr, Alasdair M.; Procyshyn, Ric M.; Honer, William G.; Pang, Catherine C.Y.

doi:10.1016/j.pharmthera.2012.04.003

Cited by 164Schizophrenia research and treatmentCardiac electrophysiology and arrhythmiasHeart Rate Variability and Autonomic Control

Cardiovascular side-effects of antipsychotic drugs: The role of the autonomic nervous system

Leung, Joanne Y.T., Barr, Alasdair M., Procyshyn, Ric M., Honer, William G., Pang, Catherine C.Y.·2012·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2012.04.003

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Abstract

Cardiovascular disease is the leading cause of death in people with severe mental disorders, and rates are proportionally greater than for other diseases such as cancer. Reports of sudden death in patients receiving antipsychotic treatment have raised concerns about the safety of antipsychotic drugs, leading to a number of recent changes in how such drugs are advertised and marketed. The majority of second generation antipsychotic drugs also have significant metabolic side-effects, such as weight gain, insulin resistance and hyperlipidemia, which may contribute indirectly to cardiovascular complications. As the use of antipsychotic drugs continues to expand into new indications and populations such as children and adolescents, a better understanding is needed of how antipsychotic drugs affect the cardiovascular system. Antipsychotic drugs interact with numerous receptors both centrally and peripherally, including monoamine receptors. The direct, non-specific pharmacological actions of antipsychotic drugs can lead to adverse cardiovascular effects, including orthostatic hypotension, tachycardia and ventricular arrhythmias. The mechanisms responsible for these antipsychotic-induced cardiovascular abnormalities have not been fully elucidated, but likely involve blockade of adrenergic or cholinergic receptors and hERG channels, in addition to impaired autonomic function. The direct and indirect effects of antipsychotic drugs on the cardiovascular system and their possible mechanisms of action are discussed in this review, where both preclinical and clinical findings are integrated.

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APs influence autonomic functioning by binding and inhibiting dopamine D2, α-adrenergic and cholinergic M3 neurotransmitter receptors in the central and peripheral nervous system which, synergistically, may induce cardiometabolic side-effects.
“APs influence autonomic functioning by binding and inhibiting dopamine D2, α-adrenergic and cholinergic M3 neurotransmitter receptors in the central and peripheral nervous system which, synergistically, may induce these cardiometabolic side-effects100,101.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [100]

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Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis
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Drug-Related Orthostatic Hypotension: Beyond Anti-Hypertensive Medications
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Authors: Leung, J. Y. T., Barr, A. M., Procyshyn, R. M., Honer, W. G., & Pang, C. C. Y.
Affiliations: University of British Columbia (CA)
Corresponding author: Barr, Alasdair M.
ORCID: Barr, Alasdair M.
Procyshyn, Ric M.
Honer, William G.
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2012-08
Volume: 135
Issue: 2
Pages: 113-122
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2012.04.003
OpenAlex: W2039425202
Cited by: 163
References: 163
Citations by year: 2026: 8 · 2025: 10 · 2024: 11 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 10 · 2019: 12 · 2018: 12 · 2017: 16 · 2016: 9 · 2015: 15 · 2014: 15 · 2013: 15 · 2012: 4
FWCI: 2.11
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords: antipsychotic drugs, cardiovascular side effects, autonomic nervous system, atypical antipsychotics, sudden death, orthostatic hypotension, tachycardia, ventricular arrhythmias, hERG channel blockade, adrenergic blockade, metabolic side effects, drug safety
MeSH terms: Animals, Autonomic Nervous System, Cardiovascular Diseases, Humans, Metabolic Diseases, Antipsychotic Agents

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Cardiovascular side-effects of antipsychotic drugs: The role of the autonomic nervous system

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