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


CONCLUSIONS
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.
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Ying-Chieh
YC
Wang
Chun-Yu
CY
Chen
Terry B J
TB
Kuo
Ching-Jung
CJ
Lai
Cheryl C H
CC
Yang
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D058256:Brain Waves / Q000187:drug effects; D004562:Electrocardiography; D004569:Electroencephalography; D004576:Electromyography; D005071:Evoked Potentials / Q000187:drug effects; D005133:Eye Movements / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D012890:Sleep / Q000187:drug effects
D014150:Antipsychotic Agents