| Summary: | 碩士 === 慈濟大學 === 神經科學研究所 === 92 === 英文摘要 Antipsychotic medications have been associated with cardiovascular adverse effects and resulted in higher incidence of sudden unexplainable death in psychiatric patients than normal population. Most sudden deaths of cardiac origin are resulted from ventricular tachycardia or fibrillation, in which QTc interval prolongation and the cardiac autonomic function impairment may play an important role. The aim of this investigation is to apply power spectral analysis of heart rate variability (HRV) as a tool and recorded QTc interval from EKG to assess the potential arrythmogenic effects upon antipsychotics . Power spectral analysis was carried out in patients with schizophrenia on neuroleptic regimen therapy: haloperidol , risperdal, clozapine and in 45 healthy subjects. Another survey was performed on the single dosage of clozapine treatment subjects before and two hours after clozapine administrating. Frequency-domain of short-term, stationary HRV was performed to evaluate the R-R interval (RR), total variance (Var), low frequency power (LF, 0.04-0.15 Hz), high frequency power (HF, 0.15-0.40 Hz), low frequency power in normalized unit (LF%) and ratio of LF to HF (LF/HF). Results showed that prolonged QTc intervals were more common in haloperidal and clozapine treated patients than in controls although the PR and QRS intervals did not differ significantly. The risperdal treated groups showed no significant difference of QTc intervals than in controls. The HRV analysis showed that haloperidol and risperidal medication groups did not show significant difference in HRV components compared with control group. Clozapine medication group (mean dosage = 325mg/day) did show significant difference in lower RR, LF and HF components and when higher dosage (mean dosage = 402 mg/day) applied, clozapine would significant elated LF/HF. Clozapine medication group also show significant difference in lower RR, LF and HF components than haldol and risperidal medication groups. As in compared with normal control, clozapine in higher dosage group also show significant elated LF/HF parameter than haldol and risperidal medication groups. In the single dosage clozapine treated group, 2 hours after single dosage administrated, showed RR, LF and HF decreased but LF/HF increased significantly，to our surprise, by 20 hours after single dosage given, patient would exacerbated expyramidal symptoms accompanied with some psychotic symptoms. We concluded that patients under clozapine therapy exhibited parasympathetic modulation suppressed, elated sympathetic modulation and cardiac repolarisation change when higher dosage and single dosage applied, this may be the cause of higher sudden death rate in clozapine treated patient. Physicians should be aware of this adverse reaction. Keyword: Schizophrenia, antipsychotics, heart rate variability, QTc interval, parasympathetic activity, sympathetic activity
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