Hirschfeld Robert M A, Baker Jeffrey D, Wozniak Patricia, Tracy Katherine, Sommerville Kenneth W
University of Texas Medical Branch at Galveston, Galveston, USA.
J Clin Psychiatry. 2003 Jul;64(7):841-6. doi: 10.4088/jcp.v64n0717.
Previous studies have examined the safety and tolerability of oral-loaded divalproex sodium in the treatment of acute mania, but not the early efficacy of this dosing strategy. The purpose of this study was to evaluate the early efficacy of oral-loaded divalproex.
In this pooled analysis, 348 subjects from 3 randomized, double-blind, parallel-group, active- or placebo-controlled studies were used to compare the efficacy, safety, and tolerability of oral-loaded divalproex with standard-titration divalproex, lithium, olanzapine, or placebo. Subjects were inpatients diagnosed with acute mania associated with bipolar I disorder (DSM-III-R or -IV and SADS-Change Version). Patients were administered oral-loaded divalproex (20 or 30 mg/kg/day on days 1 and 2 followed by 20 mg/kg/day, and increased at physician's discretion), standard-titration divalproex initiated at 250 mg t.i.d. and titrated to 40-150 microg/mL, lithium (300 mg t.i.d. initial dose) titrated to 0.4 to 1.5 mEq/L, olanzapine (10 mg q.d. initial dose) up to 20 mg/day, or placebo.
The results demonstrate an early efficacy advantage for oral-loaded divalproex compared to standard-titration divalproex at days 5, 7/8, and 10. Efficacy was improved over lithium on day 7/8. There were no efficacy differences between divalproex loading and olanzapine. Divalproex loading showed greater efficacy than placebo at all time points. Divalproex loading was as well tolerated or better tolerated than the other active treatments as measured by adverse events and changes in laboratory parameters.
These results suggest the oral loading of divalproex leads to a more rapid antimanic effect when compared with standard-titration divalproex, lithium, or placebo and is better tolerated than olanzapine and as well tolerated as lithium or standard-titration divalproex.
既往研究已考察了口服负荷量丙戊酸二钠治疗急性躁狂的安全性和耐受性，但未涉及该给药策略的早期疗效。本研究的目的是评估口服负荷量丙戊酸二钠的早期疗效。
在这项汇总分析中，来自3项随机、双盲、平行组、活性药物或安慰剂对照研究的348名受试者被用于比较口服负荷量丙戊酸二钠与标准滴定法丙戊酸二钠、锂盐、奥氮平或安慰剂的疗效、安全性和耐受性。受试者为诊断为与双相I型障碍（DSM-III-R或-IV以及SADS-Change版本）相关的急性躁狂的住院患者。患者接受口服负荷量丙戊酸二钠（第1天和第2天为20或30 mg/kg/天，随后为20 mg/kg/天，并根据医生的判断增加剂量）、起始剂量为250 mg每日3次并滴定至40 - 150 μg/mL的标准滴定法丙戊酸二钠、起始剂量为300 mg每日3次并滴定至0.4至1.5 mEq/L的锂盐、起始剂量为10 mg每日1次并增至20 mg/天的奥氮平或安慰剂治疗。
结果显示，在第5天、第7/8天和第10天，与标准滴定法丙戊酸二钠相比，口服负荷量丙戊酸二钠具有早期疗效优势。在第7/8天，其疗效优于锂盐。丙戊酸二钠负荷量与奥氮平之间无疗效差异。在所有时间点，丙戊酸二钠负荷量显示出比安慰剂更好的疗效。根据不良事件和实验室参数变化衡量，丙戊酸二钠负荷量的耐受性与其他活性治疗相当或更好。
这些结果表明，与标准滴定法丙戊酸二钠、锂盐或安慰剂相比，口服负荷量丙戊酸二钠可导致更快的抗躁狂作用，且耐受性优于奥氮平，与锂盐或标准滴定法丙戊酸二钠相当。
