Impact of Antipsychotics and Anticholinergics on Autonomic Modulation in Patients With Schizophrenia
Abstract
Antipsychotics are associated with cardiovascular risk, but the relationship between their anticholinergic properties and cardiac function is not clear. We hypothesize that antipsychotics with a high muscarinic affinity (HMA) may reduce parasympathetic modulation, which should be observable by means of heart rate variability (HRV) measurement. We also assume that anticholinergics, which are commonly used in patients with schizophrenia to treat drug-induced parkinsonism, interact with antipsychotics, and this may also affect HRV. Fifty-five patients with schizophrenia were recruited into this study. Twenty-eight subjects used antipsychotics with an HMA and 27 subjects used antipsychotics with a low muscarinic affinity (LMA). Heart rate variability values between the patients on antipsychotics with HMA and those on antipsychotics with LMA were compared. Correlation and regression analysis were then performed to clarify the relationship between HMA, LMA, and HRV. The influence of anticholinergics was also assessed by correlation analysis. The HMA group showed significantly reduced low-frequency (LF) power, high-frequency (HF) power, total power (TP), and normalized LF (LF%) than the LMA group. Regression analysis supported the hypothesis that muscarinic affinity was related to LF (β = -0.447; P < 0.001), HF (β = -0.390; P = 0.002), and TP (β = -0.399; P = 0.001). The interaction between LMA and anticholinergic use also influenced LF% (β = 0.326; P = 0.006). In the LMA group, the use of anticholinergics was positively correlated with LF% and LF/HF. In the HMA group, after exclusion of the patients using anticholinergics, the equivalent dose of antipsychotics showed a negative correlation with HF. Our results suggest that the muscarinic affinity of antipsychotics affects both sympathetic and parasympathetic modulation and that anticholinergics interact with antipsychotics to influence HRV.
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There is a negative correlation between neurocardiac control and the degree of antipsychotic affinity and antagonism of muscarinic receptors, with high muscarinic affinity antipsychotics clozapine, olanzapine and quetiapine showing greater reductions in heart rate variability than low muscarinic affinity antipsychotics risperidone and aripiprazole.
“There appears to be a negative correlation between neurocardiac control and the degree of AP affinity and antagonism of muscarinic receptors (M1-M5), with high muscarinic affinity APs (clozapine, olanzapine and quetiapine) showing greater reductions in HRV than low muscarinic affinity APs (risperidone and aripiprazole)48–50.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [48]
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Huang, W., & Liao, S. (2025) · Springer eBooks · doi:10.1007/978-3-031-73368-0_164
Self-citationGhazzal, B., Hasan, I., Hasan, N., Ghazzal, Z. B., & Refaat, M. M. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1949249
- Authors
- Huang, W.-L., Chang, L.-R., Kuo, T. B. J., Lin, Y.-H., Chen, Y.-Z., & Yang, C. C. H.
- Affiliations
- National Taiwan University Hospital (TW)
- National Central University (TW)
- National Yang Ming University (TW)
- Corresponding author
- Huang, Wei-Lieh
- Chang, Li-Ren
- Lin, Yu-Hsuan
- Chen, Ying-Zai
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2013-04
- Volume
- 33
- Issue
- 2
- Pages
- 170-177
- ISSN
- 0271-0749 (ISSN-L)
- OpenAlex
- W2063369531
- Cited by
- 46
- References
- 47
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 9 · 2018: 7 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 2
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Taiwan University Hospital
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- antipsychotic drugs, anticholinergic agents, schizophrenia, heart rate variability, parasympathetic modulation, sympathetic modulation, drug-induced parkinsonism, cardiac autonomic function, low-frequency power, high-frequency power
- MeSH terms
- Adult, Cross-Sectional Studies, Female, Heart Rate, Humans, Male, Middle Aged, Receptors, Muscarinic, Regression Analysis, Schizophrenia, Antipsychotic Agents, Cholinergic Antagonists
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