阿立哌唑治疗精神分裂症的血药浓度与临床效应关系研究

Relationship between serum concentration and clinical efficacy of aripiprazole in the treatment of patients with schizophrenia

目的:研究阿立哌唑治疗精神分裂症的血药浓度与临床效应之间关系,探索阿立哌唑血药浓度的治疗窗。方法:采用前瞻性研究方法,应用非固定剂量药物治疗8周。以高效液相色谱仪测定阿立哌唑的谷浓度,阳性和阴性症状量表(PANSS)、临床总体印象-病情严重程度量表(CGI-SI)评定疗效,治疗时出现的症状量表(TESS)评定不良反应。采用受试者运筹特征曲线(ROC曲线)获得血药浓度的最佳截断值,结合四分位间距法推测阿立哌唑血药浓度的治疗窗。并分析血药浓度与药物剂量、临床疗效、不良反应等之间的相关性。结果:入组80例患者,治疗有效47例、无效29例,另外4例脱落。总的不良反应发生率为32.5%。阿立哌唑血药浓度与药物剂量、PANSS减分率及TESS分值间呈正相关,与CGI-SI分值呈负相关。药物剂量与疗效无相关性。最低有效血药浓度为363μg/L,发生不良反应的血药浓度阈值为540μg/L。有效组血药浓度的四分位间距为348～623μg/L。血药浓度在350～540μg/L的范围内疗效较好,副反应较轻。结论:阿立哌唑治疗精神分裂症的血药浓度与临床效应之间存在相关性,较适宜的治疗窗是350～540μg/L。

AIM ： To explore the relationship between serum concentration and clinical efficacy of aripiprazole in the treatment of patients with schizophrenia,and the suitable therapeutic window of aripiprazole. METHODS ： Prospective study method was adopted.The dosages of aripiprazole were unfixed for eight weeks.The trough serum concentrations were determined by high performance liquid chromatography（HPLC）.The clinical efficacy was evaluated with the Positive and Negative Syndrome Scale（PANSS） and the Clinical Global Impression-Severity of Illnes（CGI-SI）,side effects were done with the Treatment Emergent Symptom Scale（TESS）.The optimized cutoff value of serum concentration was procured by the receiver operator curve（ROC）,and the therapeutic window of aripiprazole was evaluated combining quartering interval.The correlation among serum concentration and dosage,therapeutic effect and side effect of aripiprazole were analyzed. RESULTS ：80 subjects were participated in the study,47 cases were effective,29 cases were ineffective,4 cases were lost.The total side effect incidence rate was 32.5 %.The trough serum concentration was significantly positive correlated with dosages,the decreasing ratios of PANSS scores and TESS scores,respectively,and the trough serum concentration was significantly negative correlated with CGI-SI scores.There was no significant correlation between dosages and therapeutic effect.The lowest effective trough serum concentration was 363 μg/L,the trough serum concentration threshold occurring side effects was 540 μg/L,the quartering interval of trough serum concentration in the effective group was 348-623 μg/L.The efficacy of aripiprazole was best and its side effects were mildest when serum aripiprazole levels were in the range of 350-540 μg/L. CONCLUSION ： The serum concentration of aripiprazole in the treatment of patients with schizophrenia is correlated with clinical efficacy.The suitable therapeutic window for patients treated with aripiprazole is 350-540 μg/L.