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

BMC Psychiatry. 2012 Nov 14;12:199. doi: 10.1186/1471-244X-12-199.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Autonomic Nervous System / drug effects*
  • Autonomic Nervous System / physiopathology
  • Dose-Response Relationship, Drug
  • Electrocardiography / instrumentation
  • Electrocardiography / methods
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology


  • Antipsychotic Agents