Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA 92617, USA.
Schizophr Res. 2011 Nov;132(2-3):108-13. doi: 10.1016/j.schres.2011.07.028. Epub 2011 Aug 27.
Increasing rates of placebo response have eroded placebo-control group differences in randomized controlled trials, although the reasons for this trend remain unclear. Data were extracted from the placebo arms in two identically designed 6-week studies and one 52-week study in the ziprasidone clinical trial database. The objective of this analysis was to identify distinct patterns of placebo response trajectories that could capture individual variability in the time course of change during a 1-year trial using growth mixture latent class analyses. These long-term placebo response patterns were contrasted with two 6-week schizophrenia studies. The placebo response trajectory analysis that showed 58% (Group 4) had gradual improvement in the PANSS negative subscale score (p<0.05), fewer dropouts (p<0.05) and improvement in abnormal movements, contrasted with 3 other trajectory groups that showed worsening on these measures. Almost all subjects (98%) in this symptom improvement group were treated with conventional antipsychotics just prior to placebo treatment. In contrast, the trajectory analyses showed worsening of symptoms based on PANSS total score in the 1-year trial (+15.5, SEM 2.6). Some gradual improvement of symptoms (-14.0, SEM 1.6) was also noted in 67% (n=114) of patients in the 6-week short term trials. Our findings indicate that substantial heterogeneity in placebo response occurs in both short-term and long-term trials. The placebo response trajectories appeared to depend on the efficacy measure of symptom reduction chosen, prior antipsychotic use profile, and trial durations. Further research is warranted to examine the trajectory patterns of placebo responses in independent patient populations.
安慰剂反应率的增加已经削弱了随机对照试验中安慰剂对照的差异，尽管这种趋势的原因仍不清楚。数据是从齐拉西酮临床试验数据库中两项设计相同的 6 周研究和一项 52 周研究的安慰剂组中提取出来的。本分析的目的是使用增长混合潜在类别分析，确定能够捕捉到个体在 1 年试验过程中变化时间进程的不同安慰剂反应轨迹模式。使用这些长期安慰剂反应模式来对比两项 6 周精神分裂症研究。安慰剂反应轨迹分析显示，58%（第 4 组）的 PANSS 阴性量表评分逐渐改善（p<0.05），脱落率较低（p<0.05），异常运动改善，与其他 3 个轨迹组相比，这些指标的情况恶化。在这种症状改善组中，几乎所有患者（98%）在接受安慰剂治疗前都接受了传统抗精神病药物治疗。相比之下，根据 PANSS 总分，轨迹分析显示在 1 年试验中症状恶化（+15.5，SEM 2.6）。在 6 周短期试验中，67%（n=114）的患者也观察到症状逐渐改善（-14.0，SEM 1.6）。我们的发现表明，短期和长期试验中安慰剂反应存在很大的异质性。安慰剂反应轨迹似乎取决于所选症状缓解的疗效指标、先前抗精神病药物使用情况和试验持续时间。需要进一步研究，以检查独立患者群体中安慰剂反应的轨迹模式。
