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,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. 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.
RCT Entities:
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,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. 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.
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