Efficacy of iloperidone in schizophrenia: A PANSS five-factor analysis

Background: 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. Method: 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,C9], 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. Results: 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. Conclusions: 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. (C) 2011 Elsevier B.V. All rights reserved.