Influence of antipsychotic agents on heart rate variability in male WKY rats: Implications for cardiovascular safety

Ying Chieh Wang, Chun Yu Chen, Terry B J Kuo, Ching Jung Lai, Cheryl C H Yang

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Background: Sudden cardiac death is higher among schizophrenic patients and is associated with parasympathetic hypoactivity. Antipsychotic agents are highly suspected to be a precipitating factor. Thus, we aimed to test if the antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic function, excluding the confounding effect of altered sleep structure by the drugs. Methods: In this study, haloperidol, risperidone and clozapine were given separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days. Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals were recorded at baseline and 5 days after drug treatments. Sleep scoring was based on EEG and EMG signals. Cardiac autonomic function was assessed using heart rate variability analysis. Results: Clozapine increased heart rate and suppressed cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more severe during sleep. Haloperidol tended to decrease heart rate while risperidone mildly increased heart rate; however, their effects were less obvious than those of clozapine. There was a significant drug-by-stage interaction on several heart rate variability measures. Conclusion: Taking this evidence as a whole, we conclude that haloperidol has a better level of cardiovascular safety than either risperidone or clozapine. Application of this approach to other psychotropic agents in the future will be a useful and helpful way to evaluate the cardiovascular safety of the various psychotropic medications that are in clinical use.

Original languageEnglish
Pages (from-to)216-226
Number of pages11
Issue number4
Publication statusPublished - Jun 2012
Externally publishedYes


  • Antipsychotics
  • Autonomic activity
  • Cardiovascular safety
  • Heart rate variability
  • Schizophrenia

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Psychiatry and Mental health
  • Biological Psychiatry


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