title: Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis.
abstract: OBJECTIVE
  The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.
  
  
  METHODS
  The data in this analysis were derived from a study of patients meeting DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/d (n=109) or placebo (n=100). We defined "irritability" as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability.
  
  
  RESULTS
  Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (-22.6 vs. -9.5, p<0.0001, effect size [ES]=1.4) and without (-19.9 vs. -13.8, p<0.0001, ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (-1.4 vs. -0.3, p=0.0012, ES=1.0) and the YMRS disruptive-aggressive item (-1.0 vs. -0.3, p=0.0002, ES=1.2).
  
  
  CONCLUSIONS
  In our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.
authors.affiliation: 1Department of Psychiatry and Behavioral Sciences,Baylor College of Medicine,Houston,Texas.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Swann
authors.affiliation: 2Department of Psychiatry,Massachusetts General Hospital,Boston,Massachusetts.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: 3Sunovion Pharmaceuticals Inc.,Fort Lee,New Jersey, andMarlborough,Massachusetts.
authors.forename: Joyce
authors.initials: J
authors.lastname: Tsai
authors.affiliation: 3Sunovion Pharmaceuticals Inc.,Fort Lee,New Jersey, andMarlborough,Massachusetts.
authors.forename: Yongcai
authors.initials: Y
authors.lastname: Mao
authors.affiliation: 3Sunovion Pharmaceuticals Inc.,Fort Lee,New Jersey, andMarlborough,Massachusetts.
authors.forename: Andrei
authors.initials: A
authors.lastname: Pikalov
authors.affiliation: 3Sunovion Pharmaceuticals Inc.,Fort Lee,New Jersey, andMarlborough,Massachusetts.
authors.forename: Antony
authors.initials: A
authors.lastname: Loebel
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D000069056:Lurasidone Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000069056:Lurasidone Hydrochloride
keywords: Major depressive disorder; atypical antipsychotics; irritability; lurasidone; mixed-features specifier