比較Clozapine與非Clozapine抗精神病藥物對思覺失調症病人心率變異性之影響

Comparing the Effects of Clozapine with Non-clozapine on Heart Rate Variability in Patients with Schizophrenia

目的：本研究利用無線輕便型心率探測儀，探討不同活動時段間clozapine 與其他抗精 神病藥物對慢性思覺失調症病人心律變異性之影響。方法：本研究對象為北部某精神科專科 醫院 30 名（全為男性）慢性思覺失調症住院病人，區分為 clozapine（9 名）及非 clozapine （21 名）兩組, 接受24 小時心律記錄後，要求完成三分鐘登階運動，將其心律變異記錄區 分為五個活動時段，分別為日間、夜眠、午睡、運動及運動後。結果：與非clozapine 組比 較，服用clozapine 組在五個活動時段均顯著的呈現較快的心律及較高的 low-frequency/highfrequency 比值（均p < 0.001）。而在運動後時段可以發現clozapine 組有顯著較低的HF 值 (p < 0.01)。同時在運動後心律回復率 (heart rate recovery ratio) 比較中，發現 clozapine 組比非 clozapine 組在運動後有顯著較差的心律回復性 (p < 0.01)，尤其運動後的第三及四分鐘（均 p < 0.001）。討論：本研究使用無線輕便裝置以減少個案因肢體不便而造成之誤差，結果仍 支持clozapine 會造成心律較快的共識，且顯然此影響發生在全天活動，判斷與交感神經系 統作用增強有關。而clozapine 組在運動後則呈現明顯較多副交感神經作用抑制，尤其是在 第三及四分鐘期間。由於副交感神經作用長期以來被視為因心臟疾患猝死之重要指標，本研 究結果可提供臨床個案使用clozapine 於有心臟相關疾患及預防猝死之重要參考。

Objectives: With portable wireless heart rate detector, we intended in this study to investigate autonomic nervous activities with heart rate variability analysis during different daily activities in patients with schizophrenia treated with clozapine and non-clozapine antipsychotic drugs. Methods: We enrolled 30 male inpatients with schizophrenia (9 with clozapine treatment, 21 with non-clozapine antipsychotic treatment) participated. They received a 24-hr electrocardiogram recordings during 24 hours daily-life activities as usual and 3-minute step-test exercise. Their records were manually divided into fi ve periods of activities, namely, daytime, nap, sleep, exercise, and after exercise. Results: Compared to those with non-clozapine antipsychotics, the patients with clozapine were found to be signifi - cantly associated with increased heart rates and elevated low frequency/high-frequency ratio during all fi ve daily activities (all p < 0.001). Clozapine group was also demonstrated signifi cantly decreased high frequency band power only in after- exercise state (p < 0.01). The signifi cant difference in resting heart rate recovery ratios between two groups was found (p < 0.01) especially at the third and fourth minutes after exercise (all p < 0.01). Conclusion: In line with existing studies, the results confi rmed changes in autonomic nervous activity in patients treated with clozapine, with marked difference at all day activities and heart rate recovery after exercise. These changes are primarily due to drug-related elevation in sympathetic activity and inhibition in vagal tone, independent of age, depression and severity of symptoms. The data also suggested a possible risk of cardiovascular adversity in the clozapine treatment among patients with chronic schizophrenia especially after exercises.