- Antipsychotic medication causes a wide range of predictable adverse effects, and has long been associated with sudden unexplained and unexpected death in psychiatric patients, despite controversies surrounding the issue. In light of the evidence that sudden cardiovascular-related death is associated with neuroleptic medication, we are especially interested in examining whether measurements of the power spectral analysis (PSA) of heart rate variability (HRV) are differentially affected by various antipsychotic medications. We will also examine the cases in which PAS provides information regarding the relative safety of the various groups of drugs under investigation, in terms of their influence on the sympathetic-parasympathetic balance. The primary aim of this study is to utilize spectral analysis of heart rate variability as a tool to examine the differential arythmogenic effects of antipsychotic medications. The secondary aim was to examine the QT interval in schizophrenic patients receiving this treatment. Standardized heart rate analysis was carried out in twenty-one schizophrenic patients receiving monotherapy with the following medications: treatment with 300-700 mg/day of clozapine, eighteen schizophrenic patients treated with 5-10 mg/day haloperidol, seventeen schizophrenic patients treated with 5-20 mg/day Olanzapine, and 53 healthy subjects. Our results show that schizophrenic patients treated with clozapine had significantly higher HR, lower HRV, lower high frequency (HF) and higher low frequency (LF) components compared to the patients treated with haloperidol, olanzapine, and the matched control subjects. Prolonged QTc intervals were more common in patients receiving treatment than in the control group, although the PR and QRS intervals did not differ significantly. The overall results showed that, patients treated with neuroleptic medication, especially clozapine, presented autonomic dysregulation and cardiac repolarization changes. Care should be taken in prescribing clozapine to patients prone to cardiovascular side effects.