丙戊酸钠治疗双相Ⅰ型障碍患者方案优化与实施个体化剂量的研究  

Optimized therapeutic scheme and individualized dosage of sodium valproate in patients with bipolar disorder sub-type Ⅰ

作　　者：杨甫德[1] 李娟[1] 谭云龙[1] 陈大春[1] 姚复新[1] 张兴理[1] 李尚明[1] 冀成君[1] 黄文升[1] 张广慧[1] 吉中孚[1] 舒良[2] 

机构地区：[1]北京回龙观医院临床精神药理研究室,北京100096 [2]北京大学第六医院,北京100083

出　　处：《中国新药杂志》2009年第1期47-52,共6页Chinese Journal of New Drugs

基　　金：首都医学发展基金(2003-3069)

摘　　要：目的：探讨丙戊酸钠联合氯硝西泮治疗对双相障碍Ⅰ型躁狂发作患者的疗效和安全性。方法：共入组60例患者，随机分入丙戊酸钠联合氯硝西泮治疗组与丙戊酸钠联合氟哌啶醇对照组进行治疗，丙戊酸钠实施个体化药物剂量调整方案。于基线时、治疗第1，2，3，4，6，8，10，12，16周末，分别采用临床总体印象疾病总体严重度量表-双相障碍版（CGI—BP）、Young躁狂评定量表（YMRS）、简明精神病量表（BPRS）、汉密尔顿抑郁评定量表（HAMD-21）、功能总体评定量表评定（GAS）评定疗效和测定丙戊酸钠血浓度。在基线状态、治疗第4，8，12，16周时，进行血生化、血常规、尿常规、ECG检查以及药物治疗副反应量表（TESS）评定，以评价安全性。结果：①2组自治疗1周末CGI—BP（5．0±0．4，4．6±0．6）和YMRS（26．7±3．7，26．0±3．8）得分均较治疗前（5．3±0．5，5．2±0．4；30．4±1．5，29．7±1．4）有明显下降，差异有显著性（P〈0．05），自治疗第4周起，社会功能也较基线时有显著改善，而两组之间在上述指标方面的差异均无显著性（P〉0．05）。治疗16周末，试验组和对照组的缓解率分别为93．3％和90％。②对照组（63％）出现不良反应的总发生率高于试验组（40％）。（④丙戊酸钠的有效治疗血浓度范围为76～124μg·mL^-1，有效维持血浓度范围为67～87μg·mL^-1。结论：丙戊酸钠联合氯硝西泮治疗双相Ⅰ型障碍的疗效同丙戊酸钠联合氟哌啶醇相当，且转相率低，不良反应更少，安全性更高。Objective： To evaluate the clinical efficacy and safety of sodium valproate combined with clonazepam in treating patients with bipolar disorder sub-type Ⅰ and mixed episodes. Methods： Eligible patients （ n = 60） were randomized to receive sodium valproate combined with clonazepam （SVC group） or haloperidol （SVH group） , the dosages of sodium valproate were individualized. The clinical global impress scale-bipolar disorder （CGI-BP）, Young mania rating scale （YMRS）, brief psychiatric rating scale （BPRS）, Hamilton depression scale （HAMD-21）, and global assessment scale were assessed, and plasma concentration of sodium valproate was as- sayed before （baseline） and 1 , 2, 3,4, 6, 8, 10, 12, 16 weeks after the treatments. Blood routine and biochemistry, urine routine and electrocardiogram were determined, and treatment emergent symptoms scale （TESS） was assessed for evaluating safety before and 4, 8, 12, 16 weeks after the treatments. Results： ① The scores of CGIBP （5.0±0.4 and 4.6 ±0.6） and YMRS （26.7 ±3.7 and 26.0 ±3.8） 1 week after the treatment in both SVC and SVH groups were markedly lower than the baseline scores （5.3 ± 0.5 and 5.2 ± 0.4 ; 30.4 ± 1.5 and 29.7 ± 1.4 ; P 〈 0.05 for each score）. The social function was significantly improved since the 4th week, and the effectiveness was similar in both groups. At the end of 16th week, the effective rates were 93% and 90% , respeetively, in SVC and SVH groups. ② During the treatments, the observable side effeets were higher in SVH group （63%） than SVC group （40%）. ③The plasma effective concentration of sodium valproate was （76 - 124） μg.mL^-1 ; the effeetive maintainable concentration was （67 -87） μg. mL^-1. Conclusion： Compared to sodium valproate combined with haloperidol, the efficacies of combination with clonazepam are equivalent in treating patients with bipolar disorder sub-type Ⅰ. Moreover , the prevalence of turning to other type episodes and side effects are lower.

关 键 词：双相障碍Ⅰ型 丙戊酸钠 疗效 不良反应 

分 类 号：R971[医药卫生—药品]