小剂量利培酮强化抗抑郁剂治疗双相抑郁发作的疗效和安全性研究

Efficacy and safety of low dosage risperidone added on valproate and citalopram in the treatment of acute bipolar depression

目的考察小剂量利培酮强化抗抑郁剂治疗对双相抑郁发作的疗效和安全性。方法符合入组标准的住院患者,先接受2周的丙戊酸钠(valproate,VPA)合并西酞普兰(citalopram,CIT)治疗。2周末相对于基线的蒙哥马利抑郁量表(Montgomery and Asberg Depression Scale,MADRS)减分率<50%者按照1∶1的比例采用数字表法随机分配至丙戊酸钠+西酞普兰组(VPA+CIT)或丙戊酸钠+西酞普兰+利培酮组(risperidone,RIS),接受为期6周的随机开放治疗,进行疗效评价及安全性评价。结果治疗终点VPA+CIT+RIS组和VPA+CIT组MADRS、简明精神病量表(Brief Psychiatric Rating Scale,BPRS)、临床疗效总评量表-严重程度(Clinical Global Impression-severity of illness,CGI-S)和临床疗效总评量表-改善程度(Clinical Global Impressionimprovement of illness,CGI-I)评分较导入期末均明显降低,其中MADRS、BPRS、杨氏躁狂量表(Young Mania Rating Scale,YMRS)两组对比差异没有统计学意义(P>0.05)。CGI-I 2组对比,差异具有统计学意义(P<0.05)。BPRS阳性因子评分两组对比,差异没有统计学意义(P>0.05)。随机治疗第1周末BPRS阳性因子评分VPA+CIT+RIS组较VPA+CIT组明显降低,差异有统计学意义(P<0.05),显示VPA+CIT+RIS组较VPA+CIT组在改善阳性精神病性症状方面起效更快。在随机治疗第2周,VPA+CIT+RIS组有效率为66.0%,VPA+CIT组为33.3%,显示VPA+CIT+RIS组较VPA+CIT组起效更快。结论 VPA+CIT+RIS与VPA+CIT治疗双相抑郁发作均安全有效。在快速起效及降低转相风险方面,VPA+CIT+RIS组优于VPA+CIT组。

Objective To evaluate the augmentation efficacy and safety of low dosage risperidone, added on the usual treatment （ valproate and citalopram） in the acute treatment of bipolar depression. Methods A total of 46 inpatients with a diagnostic criteria for acute depression episode with bipolar disorder according to DSM-IV-TR were first given valproate and citalopram treatment. The subjects who achieve little clinical response（ i. e. reduction from baseline in total MADRS score by〈50%） at the end of 2-week will enter into the randomized open-label 6-week treatment phase. The eligible subjects will be randomized to treatment with valproate ＆amp; citalopram or valproate ＆amp; citalopram ＆amp; risperidone in a 1：1 ratio. Efficacy rating scales to be used in the study include MADRS, YMRS, BPRS（ total score and positive subscale）, CGI-S, and CGI-I. The evaluations of safety and tolerability include SAS, treatment-emergent mania, clinical laboratory tests, vital signs , ECG, and adverse events reports. Results At the end of treatment, the scores of MADRS, BPRS, GIC-I, and CGI-S in both treatment groups decreased significantly compared with the end of run-in period . There were statistically significant differences between groups in YMRS and CGI-I（P〈0. 05）, but not in MADRS and BPRS（total score and positive subscale）. At week 1 of randomized treatment period, the scores of BPRS positive subscale decreased sharply in the VPA＋CIT＋RIS group than those in the VPA＋CIT group, the difference was statistically significant（P〈0. 05）. At week 2 of randomized treatment period, the response rates of the VPA＋CIT＋RIS group was superior to the VPA＋CIT group, the difference was statistically significant（P〈0. 05）. It suggested that the time to response of the VPA＋CIT＋RIS group is shorter than that of the VPA＋CIT group. Conclusion Both VPA＋CIT＋RIS and VPA＋CIT are efficacious and well tolerated for the acute treatment of bipolar depression. For the treatment of psychosis and reducing the treatment-emergent mania, the VPA＋CIT group was better than the VPA＋CIT group.