Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies
Stephen Marder, W Wolfgang Fleischhacker, Willie Earley, Kaifeng Lu, Yan Zhong, György Németh, István Laszlovszky, Erzsébet Szalai, Suresh Durgam, Stephen Marder, W Wolfgang Fleischhacker, Willie Earley, Kaifeng Lu, Yan Zhong, György Németh, István Laszlovszky, Erzsébet Szalai, Suresh Durgam
Abstract
Schizophrenia affects various symptom domains, including positive and negative symptoms, mood, and cognition. Cariprazine, a dopamine D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, with preferential binding to D3 receptors, is approved for the treatment of adult patients with schizophrenia (US, Europe) and mania associated with bipolar I disorder (US). For these investigations, data were pooled from 3 positive, 6-week, double-blind, placebo-controlled, phase II/III trials of cariprazine in patients with acute exacerbation of schizophrenia (NCT00694707, NCT01104766, NCT01104779); 2 trials were fixed-dose and 1 trial was flexible-dose. Post hoc analyses evaluated mean change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) -derived symptom factors (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, anxiety/depression) and PANSS single items for cariprazine (1.5-9.0 mg/d) versus placebo. P values were not adjusted for multiple comparisons. At week 6, statistically significant differences versus placebo were seen for cariprazine on all 5 PANSS factors (P < 0.01 all). Effects sizes ranged from 0.21 (anxiety/depression) to 0.47 (disorganized thought). Dose-response analysis from the fixed-dose studies found significant differences for all cariprazine doses (1.5, 3.0, 4.5, and 6.0 mg/d) versus placebo in PANSS total score, and in negative symptom and disorganized thought factor scores (P < 0.001). Differences between cariprazine and placebo were also statistically significant on 26 of 30 PANSS single items (P < 0.05). In these post hoc analyses, cariprazine was effective versus placebo in improving all 5 PANSS factor domains, suggesting that it may have broad-spectrum efficacy in patients with acute schizophrenia.
Keywords: 5-HT1a serotonin receptor; Atypical antipsychotic; Cariprazine; Dopamine receptor; Schizophrenia.
Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.
Source: PubMed