New York University School of Medicine, New York, NY, USA.
Schizophr Res. 2011 Sep;131(1-3):75-81. doi: 10.1016/j.schres.2011.05.018. Epub 2011 Jun 22.
The Positive and Negative Syndrome Scale (PANSS) total score is widely used to assess antipsychotic efficacy, however schizophrenia is a multi-dimensional disorder. We conducted a 5-factor analysis for evaluating the efficacy of iloperidone vs. placebo across these different domains in the treatment of schizophrenia.
The 5-factor model was determined from pooled data from 7 clinical trials (4 placebo- and active-controlled and 3 non-inferiority active-comparator trials of iloperidone) in schizophrenia (N=3580).Five factors were derived (excitement/hostility [P4,P7,G8,G14], depression/anxiety [G1,G2,G3,G4,G6], cognition [P2,N5,N7,G5,G10,G11,G12,G13,G15], positive [P1,P3,P5,P6,G9], and negative [N1,N2,N3,N4,N6,G7,G16]) from a factor analysis on the covariance matrix of 30 baseline PANSS items using a varimax rotation; factors retained had eigenvalues of ≥ 0.5. These newly derived 5 factors differ only slightly from other 5-factor analyses published by others using different datasets. The analysis of covariance model was then applied to assess these efficacy outcomes from the 4-6 week double-blind placebo and active controlled clinical trials of iloperidone.
Based on the placebo-controlled trials, iloperidone improvements from baseline (least squared mean change ± standard error) were as follows: excitement/hostility, 0.4 ± 0.21 for 10-16 mg, 0.6 ± 0.43 for 20-24 mg vs. -1.0 ± 0.23 for placebo; P<0.001 for both iloperidone doses vs. placebo; depression/anxiety, 1.9 ± 0.21 for 10-16 mg, 1.9 ± 0.41 for 20-24 mg vs. 1.1 ± 0.22 for placebo; P<0.05 for 10-16 mg dose vs. placebo; cognition, 2.8 ± 0.35 for 10-16 mg, 3.9 ± 0.69 for 20-24 mg vs. 1.6 ± 0.38 for placebo; P<0.05 for both iloperidone doses vs. placebo; positive, 3.7 ± 0.26 for 10-16 mg, 4.1 ± 0.53 for 20-24 mg vs. 2.7 ± 0.29 for placebo; P<0.05 for both iloperidone doses vs. placebo; and negative, 2.2 ± 0.29 for 10-16 mg, 2.5 ± 0.58 for 20-24 mg vs. 1.3 ± 0.32 for placebo; P<0.05 for 10-16 mg vs. placebo. Active controls validated iloperidone efficacy.
Iloperidone demonstrated positive treatment effects on these newly derived PANSS factors. The 10-16 mg and 20-24 mg dose groups had similar efficacy on the PANSS factors, with the exception of the depression/anxiety and negative factors, on which the 10-16 mg dose group showed statistical separation from placebo and the 20-24 mg dose group did not. At 6 weeks, the lack of separation from placebo for the higher dose group may have been due to the much smaller sample size in that group.
阳性与阴性症状量表（PANSS）总分广泛用于评估抗精神病药的疗效，但精神分裂症是一种多维障碍。我们进行了 5 因子分析，以评估伊洛哌酮与安慰剂在治疗精神分裂症的不同领域中的疗效。
从 7 项临床试验（4 项安慰剂对照和活性对照试验，3 项非劣效性活性对照试验）的合并数据中确定 5 因子模型（N=3580）。从 30 个基线 PANSS 项目的协方差矩阵中使用最大方差旋转进行因子分析，得出 5 个因子（兴奋/敌意[P4，P7，G8，G14]，抑郁/焦虑[G1，G2，G3，G4，G6]，认知[P2，N5，N7，G5，G10，G11，G12，G13，G15]，阳性[P1，P3，P5，P6，G9]，和阴性[N1，N2，N3，N4，N6，G7，G16]）；保留的因子具有≥0.5 的特征值。这些新得出的 5 个因子与其他人使用不同数据集发布的其他 5 因子分析仅略有不同。然后应用协方差分析模型评估伊洛哌酮在 4-6 周双盲安慰剂和活性对照临床试验中的这些疗效结果。
基于安慰剂对照试验，伊洛哌酮从基线的改善（最小二乘均值变化±标准误差）如下：兴奋/敌意，10-16mg 组为 0.4±0.21，20-24mg 组为 0.6±0.43，安慰剂组为-1.0±0.23；10-16mg 和 20-24mg 剂量组均显著优于安慰剂（P<0.001）；抑郁/焦虑，10-16mg 组为 1.9±0.21，20-24mg 组为 1.9±0.41，安慰剂组为 1.1±0.22；10-16mg 剂量组显著优于安慰剂（P<0.05）；认知，10-16mg 组为 2.8±0.35，20-24mg 组为 3.9±0.69，安慰剂组为 1.6±0.38；10-16mg 和 20-24mg 剂量组均显著优于安慰剂（P<0.05）；阳性，10-16mg 组为 3.7±0.26，20-24mg 组为 4.1±0.53，安慰剂组为 2.7±0.29；10-16mg 和 20-24mg 剂量组均显著优于安慰剂（P<0.05）；阴性，10-16mg 组为 2.2±0.29，20-24mg 组为 2.5±0.58，安慰剂组为 1.3±0.32；10-16mg 剂量组显著优于安慰剂（P<0.05）。活性对照验证了伊洛哌酮的疗效。
伊洛哌酮在这些新得出的 PANSS 因子上显示出积极的治疗效果。10-16mg 和 20-24mg 剂量组在 PANSS 因子上具有相似的疗效，但抑郁/焦虑和阴性因子除外，在这些因子上，10-16mg 剂量组与安慰剂有统计学差异，而 20-24mg 剂量组则没有。在 6 周时，由于该组的样本量较小，高剂量组与安慰剂分离不明显。
