氯氮平治疗精神分裂症及血药浓度研究

Research for clozapine in schizophrenia and the relationship between plasma clozapine concentration and clinical response

目的 :探讨氯氮平治疗的适宜剂量及血药浓度与临床效应的关系。 方法 :氯氮平治疗精神分裂症 6周共 6 2例 (15 0 m g/d组 2 1例 ,30 0 mg/d组 2 0例 ,45 0 mg/d组 2 1例 )。用阳性和阴性症状量表 (PANSS)和副反应量表 (TESS)评定疗效及副反应。在治疗第 2、 4、 6周末晨服药前测血药浓度。 结果 :3种剂量组间有效率、 PANSS减分值、 TESS增分值均无显著差异 (P>0 .0 5 ) ,不同时段 PANSS分值改变也无明显组间差异 ,提示 3组间不仅疗效相当且起效快慢也无明显差异。完成血药浓度测定者 42例 ,有效血浓度低于以往研究推荐的 35 0～ 45 0μg/L。提示氯氮平血浓度治疗窗尚有较大探讨余地。 结论 :在一定范围内低剂量氯氮平能取得与高剂量同样的疗效 ,对临床工作中避免盲目大剂量用药有指导意义 ,同时也有助于人们对氯氮平血浓度治疗窗有新的认识。

Objective:This study tried to explore the optimal dosage of clozapine in the treatment of schizophrenia,and examine the relationship between plasma concentration of clozapine and clinical response. Method:62 schizophrenic patients diagnosed according to CCMD 2 R were randomly assigned to treat with 150,300 or 450mg of clozapine daily.Mental symptoms were monitored at baseline and at 1,2,4,6 week with the positive and negative symptom scale (PANSS).The side effects were monitored with the treatment emergent symptom scale (TESS).Plasma clozapine levels were obtained every 2 weeks. Results:No statistically significant differences in clinical improvement were found among the three dosages,nor in the side effects.Patients showing improvement had an average plasma concentration (329 2±75 5μg/L) lower than the optimal levels (350~450μg/L) recommended by former researches. Conclusion:It is confirmed that the dose of 150mg/d of clozapine appears to be as effective as higher doses in the treatment of schizophrenia.The target plasma clozapine concentration for satisfying efficacy warrants further research.