Open Access Open Badges Research article

Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia

Yohko Iwamoto12, Chiaki Kawanishi1*, Ikuko Kishida12, Taku Furuno1, Mami Fujibayashi34, Chie Ishii2, Norio Ishii2, Toshio Moritani3, Masataka Taguri5 and Yoshio Hirayasu1

Author Affiliations

1 Department of Psychiatry, Yokohama City University School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

2 Fujisawa Hospital, Kanagawa Prefecture, Japan

3 Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan

4 The Division of Physical and Health Education, Setsunan University, Osaka, Japan

5 Department of Biostatistics and Epidemiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan

For all author emails, please log on.

BMC Psychiatry 2012, 12:199  doi:10.1186/1471-244X-12-199

Published: 14 November 2012



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.


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.


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.


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.

Adverse drug effect; Antipsychotic drug; Autonomic nervous system; Heart rate variability; Schizophrenia