Tohen Mauricio, Ketter Terence A, Zarate Carlos A, Suppes Trisha, Frye Mark, Altshuler Lori, Zajecka John, Schuh Leslie M, Risser Richard C, Brown Eileen, Baker Robert W
Lilly Research Laboratories, IN 46285, USA.
Am J Psychiatry. 2003 Jul;160(7):1263-71. doi: 10.1176/appi.ajp.160.7.1263.
Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex.
This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest.
Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness.
In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.
很少有双盲试验比较过用于双相情感障碍的药物的长期疗效和安全性。作者报告了一项奥氮平与丙戊酸镁为期47周的对比研究。
这项为期47周的随机双盲研究，将灵活给药的奥氮平（5 - 20毫克/天）与丙戊酸镁（500 - 2500毫克/天）用于双相情感障碍的躁狂或混合发作进行比较（N = 251）。唯一允许使用的其他精神活性药物是用于躁动的劳拉西泮。主要疗效指标是杨氏躁狂评定量表；事先在方案中定义的纳入阈值分数≥20，缓解阈值分数≤12，复发阈值分数≥15。分析技术包括用于从基线变化的混合模型重复测量方差分析、用于分类比较的Fisher精确检验（双侧）以及对感兴趣事件发生时间的Kaplan - Meier估计。
在47周的时间里，奥氮平组杨氏躁狂评定量表评分的平均改善程度显著更大。奥氮平组有症状的躁狂缓解的中位时间显著短于丙戊酸镁组，分别为14天和62天。在47周内，有症状的躁狂缓解率（分别为56.8%和45.5%）以及随后躁狂或抑郁复发率（42.3%和56.5%）在两种治疗之间无显著差异。在奥氮平治疗期间显著更频繁出现的治疗中出现的不良事件是嗜睡、口干、食欲增加、体重增加、静坐不能和高丙氨酸转氨酶水平；丙戊酸镁组的是恶心和紧张。
在这项对急性双相躁狂进行的为期47周的研究中，奥氮平比丙戊酸镁出现症状缓解更快，总体躁狂改善更大，但双相复发率没有差异。
