Dubé Sanjay, Tollefson Gary D, Thase Michael E, Briggs Susan D, Van Campen Luann E, Case Michael, Tohen Mauricio
Lilly Research Laboratories, Indianapolis, IN 46285, USA.
Bipolar Disord. 2007 Sep;9(6):618-27. doi: 10.1111/j.1399-5618.2007.00491.x.
The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination.
Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed. The Montgomery-Asberg Depression Rating Scale measured depressive symptoms. Multiple analytic methods were applied, including traditional (mean differences) analysis, pattern analysis, survival analysis of sustained response, mixed-effects regression, and area-under-the-curve analysis.
Traditional analysis showed significantly greater improvement in depression scores at week 1 for olanzapine/fluoxetine combination versus placebo (-9.55 versus -5.08, p < 0.001) and for olanzapine versus placebo (-8.31 versus -5.08, p < 0.001). Pattern analysis revealed olanzapine/fluoxetine combination had a significantly greater percentage of early persistent responders than placebo or olanzapine (32.4% versus 12.7%, p < 0.001; and 18.3%, p < 0.05, respectively). Survival analysis showed a significantly shorter time to sustained response for the combination versus placebo (p < 0.001), for olanzapine versus placebo (p = 0.04), and for the combination versus olanzapine (p = 0.03). Mixed-effects regression analysis revealed a significant therapy-by-time interaction (p < 0.001). Early area-under-the-curve analysis revealed a significantly greater percentage of improvement for the combination versus placebo (26.7% versus 13.9%, p < 0.001) and for olanzapine versus placebo (22.0% versus 13.9%, p < 0.001).
Based on consistent results from related methods of measuring onset, olanzapine/fluoxetine combination demonstrated rapid onset of antidepressant effect (within 7 days) compared to placebo that was sustained over 8 weeks of treatment in a sample of BD patients. Using multiple statistical techniques may help profile a drug's onset of effect.
本次分析研究了奥氮平/氟西汀联合用药抗抑郁作用的起效情况。
这些事后分析的数据来自一项在双相抑郁症（BD）患者中比较奥氮平、安慰剂及奥氮平/氟西汀联合用药的临床试验。研究对象为833例符合《精神疾病诊断与统计手册》第四版（DSM-IV）标准的双相I型障碍抑郁发作患者。采用蒙哥马利-阿斯伯格抑郁评定量表（Montgomery-Asberg Depression Rating Scale）评估抑郁症状。应用了多种分析方法，包括传统（均值差异）分析、模式分析、持续反应生存分析、混合效应回归分析及曲线下面积分析。
传统分析显示，在第1周时，奥氮平/氟西汀联合用药组的抑郁评分改善程度显著大于安慰剂组（分别为-9.55和-5.08，p<0.001），奥氮平组也显著大于安慰剂组（分别为-8.31和-5.08，p<0.001）。模式分析表明，奥氮平/氟西汀联合用药组早期持续有效者的比例显著高于安慰剂组或奥氮平组（分别为32.4%和12.7%，p<0.001；以及18.3%，p<0.05）。生存分析显示，联合用药组达到持续反应的时间显著短于安慰剂组（p<0.001），奥氮平组也短于安慰剂组（p = 0.04），联合用药组短于奥氮平组（p = 0.03）。混合效应回归分析显示治疗与时间存在显著交互作用（p<0.001）。早期曲线下面积分析显示，联合用药组的改善百分比显著高于安慰剂组（分别为26.7%和13.9%，p<0.001），奥氮平组也高于安慰剂组（分别为22.0%和13.9%，p<0.001）。
基于相关起效测量方法的一致结果，在双相抑郁症患者样本中，与安慰剂相比，奥氮平/氟西汀联合用药表现出快速的抗抑郁起效（7天内），且在8周治疗期内持续有效。使用多种统计技术可能有助于描绘药物的起效情况。
