title: A placebo-controlled crossover study of iloperidone augmentation for residual anger and irritability in major depressive disorder.
abstract: BACKGROUND
  Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone's safety and efficacy as an augmentation agent in outpatients with partially remitted major depressive disorder (MDD) with residual symptoms of anger and irritability.
  
  
  METHODS
  A total of 13 outpatients with partially remitted MDD [currently treated with selective serotonin reuptake inhibitors (SSRIs)] received four weeks of iloperidone or placebo, followed by one week of washout. Patients were then crossed over to the other treatment arm for 4 weeks. Treatment arms were randomized and double blind; and two sites were used for the study. Analyses compared treatment response using the Symptom Questionnaire (SQ) Anger/Hostility Subscale as the primary outcome measure.
  
  
  RESULTS
  There was no significant differential effect of iloperidone × weeks on the SQ Anger/Hostility Subscore over the course of the study, compared with placebo × weeks, regardless of administration order (p = 0.77).
  
  
  CONCLUSIONS
  Iloperidone did not significantly outperform placebo on measures of anger or irritability in patients with partially remitted MDD and residual anger/irritability.
authors.affiliation: Massachusetts General Hospital, Depression Clinical and Research Program, Boston, MA, USA Harvard Medical School, Boston, MA.
authors.forename: Dawn F
authors.initials: DF
authors.lastname: Ionescu
authors.affiliation: Massachusetts General Hospital, Depression Clinical and Research Program, Harvard Medical School, 55 Fruit Street, Bulfinch 351, Boston, MA 02114, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: Massachusetts General Hospital, Depression Clinical and Research Program, Boston, MA, USA.
authors.forename: Daniel Ju Hyung
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Massachusetts General Hospital, Depression Clinical and Research Program, Boston, MA, USA Harvard Medical School, Boston, MA.
authors.forename: Lee
authors.initials: L
authors.lastname: Baer
authors.affiliation: Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.affiliation: Massachusetts General Hospital, Depression Clinical and Research Program, Boston, MA, USA Harvard Medical School, Boston, MA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cusin
keywords: anger; augmentation; iloperidone; irritability; major depressive disorder