Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia
Open accessAbstract
Background: Antipsychotic drugs are considered a trigger factor for autonomic dysregulation, which has been shown to predict potentially fatal arrhythmias in schizophrenia. However, the dose-dependent effect of antipsychotic drugs and other psychotropic drugs on autonomic nervous system (ANS) activity remain unclear. The purpose of this study was to investigate the dose-dependent effect of antipsychotic drugs and other clinical factors on ANS activity in an adequate sample size of patients with schizophrenia. Methods: A total of 211 Japanese patients with schizophrenia and 44 healthy subjects participated in this study. ANS activity was assessed by means of heart rate variability (HRV) power spectral analysis. Antipsychotic drug treatment and various clinical factors were investigated for each participant. The patient group was categorized into three subgroups according to daily dose of antipsychotic drug, and HRV was compared between groups. Results: The results showed significantly decreased low-frequency and high-frequency components of HRV in the patient group compared to the control group. The high-dose group showed a significantly lower HRV than the medium-dose group and an even lower HRV than the low-dose group. In addition, a significant association between HRV and antipsychotic drug dose was identified by multiple regression analysis. HRV was not associated with age, sex, body mass index, duration of illness, or daily dose of other psychotropic drugs. Conclusion: These results suggest that antipsychotic drugs exert a significant dose-dependent effect on the extent of decline in ANS activity, and that optimal antipsychotic medication is required to avoid possible cardiovascular adverse events in patients with schizophrenia.
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The effects of anticholinergic antiparkinsonian agents on ANS activity may be related not only to their anticholinergic affinity but also to dose.
“In addition, it should be noted that this study did not find any effects of anticholinergic antiparkinsonian agents on ANS activity; however, given the low dose of these agents in the study (3.2 ± 1.5 mg/day biperiden equivalent), the effects of such agents may not only be related to their anticholinergic affinity but also dose.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [33]
The Discussion and conclusion reports no correlation between ANS activity and antiparkinsonian-drug dose at 3.2 ± 1.5 mg/day (biperiden equivalent), but suggests the drugs might affect ANS activity at higher doses. It does not link the effects of antiparkinsonian agents to their anticholinergic affinity; its discussion of receptor affinity concerns antipsychotic drugs. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPatients with schizophrenia have relatively preserved sympathetic functioning and do not differ significantly from healthy controls.
“Consistent with the findings of several previous studies31–34, these results imply that patients with SCZ have relatively preserved sympathetic functioning and do not differ significantly with HCs.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [33]
Significant decreases in heart rate variability and ANS activity are only observed with antipsychotic doses of at least 501 mg/day chlorpromazine equivalent.
“More specifically, significant decreases in HRV and ANS activity were only observed with AP doses ≥501 mg/day chlorpromazine equivalent.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [33]
The extent to which antipsychotics exacerbate autonomic dysfunction in schizophrenia may depend on the type of antipsychotic and its mechanisms of action.
“The extent to which APs exacerbate autonomic dysfunction in SCZ may be dependent on the type of AP taken and their respective mechanisms of action in the body (i.e., interaction with different neurotransmitter systems/receptors) (Fig. 2)33.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [33]
The study did not find any effects of anticholinergic antiparkinsonian agents on ANS activity.
“In addition, it should be noted that this study did not find any effects of anticholinergic antiparkinsonian agents on ANS activity; however, given the low dose of these agents in the study (3.2 ± 1.5 mg/day biperiden equivalent), the effects of such agents may not only be related to their anticholinergic affinity but also dose.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [33]
Exacerbation of autonomic dysfunction with antipsychotics is dose dependent, with statistically significant associations between daily dose of antipsychotic drugs and parasympathetic nervous system activity.
“Furthermore, the exacerbation of autonomic dysfunction with APs has been found to be dose dependent, with multiple regression analyses revealing statistically significant associations between daily dose of AP drugs and PSNS activity33.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [33]
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References 41 · Cited by 56
- Authors
- Iwamoto, Y., Kawanishi, C., Kishida, I., Furuno, T., Fujibayashi, M., Ishii, C., Ishii, N., Moritani, T., Taguri, M., & Hirayasu, Y.
- Affiliations
- Yokohama City University (JP)
- Setsunan University (JP)
- Kyoto University (JP)
- Corresponding author
- Kawanishi, Chiaki
- Venue
- BMC Psychiatry
- Published
- 2012-11-14
- Volume
- 12
- Issue
- 1
- Pages
- 199-199
- ISSN
- 1471-244X (ISSN-L)
- PMC
- PMC3534356
- OpenAlex
- W2023490381
- Cited by
- 56
- References
- 41
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 3
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- antipsychotic drugs, dose-dependent effects, autonomic nervous system activity, schizophrenia, heart rate variability, autonomic dysfunction, cardiovascular adverse events, arrhythmia risk, psychotropic drugs
- MeSH terms
- Adult, Aged, Autonomic Nervous System, Dose-Response Relationship, Drug, Electrocardiography, Female, Heart Rate, Humans, Japan, Male, Middle Aged, Psychiatric Status Rating Scales, Schizophrenia, Antipsychotic Agents
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