title: The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials.
abstract: OBJECTIVE
  Although most patients with schizophrenia are not aggressive, individuals with the disorder have increased risk of hostile behavior. Cariprazine, a dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, was evaluated for antihostility effects in patients with schizophrenia.
  
  
  METHODS
  Post hoc analyses were conducted using pooled data from 3 positive randomized, placebo-controlled, phase 2/3 studies in inpatients (18-60 years) with acute exacerbation of schizophrenia according to DSM-IV-TR criteria; data were collected between 2008 and 2011. The principal post hoc outcome was mean change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) hostility item (P7); separate analyses adjusted for certain PANSS positive symptoms and sedation covariates. Analyses were based on the pooled intent-to-treat population (N = 1,466) using a mixed-effects model for repeated measures approach; separate analyses were conducted in subgroups categorized by baseline hostility item scores (P7: ≥ 2, ≥ 3, ≥ 4).
  
  
  RESULTS
  The least squares mean difference (LSMD) in change from baseline to week 6 was statistically significant on all PANSS hostility item analyses in favor of cariprazine versus placebo: unadjusted (-0.28; P < .0001), adjusted for PANSS positive symptoms (-0.12; P < .05), adjusted for positive symptoms plus sedation (-0.12; P < .05). The magnitude of change for cariprazine increased with greater baseline hostility (LSMD vs placebo for ≥ 2, ≥ 3, ≥ 4 subgroups: -0.32, -0.37, -0.51, respectively; P < .01 all).
  
  
  CONCLUSIONS
  Significant improvement on the hostility item was seen in cariprazine- versus placebo-treated patients with schizophrenia; the effect of cariprazine increased with greater levels of baseline hostility.
  
  
  BACKGROUND
  ClinicalTrials.gov identifiers: NCT00694707, NCT01104766, and NCT01104779.
authors: 11 Medical Park Dr, Ste 106, Pomona, NY 10970 citrome@cnsconsultant.com.
authors: Leslie
authors: L
authors: Citrome
authors: Suresh
authors: S
authors: Durgam
authors: Kaifeng
authors: K
authors: Lu
authors: Paul
authors: P
authors: Ferguson
authors: István
authors: I
authors: Laszlovszky
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D005260:Female; D006791:Hostility; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine