title: Lurasidone in the treatment of bipolar depression with mixed (subsyndromal hypomanic) features: post hoc analysis of a randomized placebo-controlled trial.
abstract: OBJECTIVE
  Mixed (subsyndromal hypomanic) features are prevalent in patients with bipolar depression and are associated with more severe and complex illness, including increased risk for suicide attempts, higher switch to mania during antidepressant therapy, and a higher rate of recurrence. The aim of this post hoc analysis was to evaluate the efficacy and safety of lurasidone in the treatment of patients with bipolar depression presenting with mixed features.
  
  
  METHODS
  Patients with a DSM-IV-TR diagnosis of major depressive episode associated with bipolar I disorder, with or without rapid cycling, and with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20 and a Young Mania Rating Scale (YMRS) score ≤ 12 were randomly assigned to 6 weeks of double-blind, once-daily treatment with lurasidone 20-60 mg, lurasidone 80-120 mg, or placebo. The presence of mixed features was defined as a YMRS score ≥ 4 at study baseline. Efficacy analyses included change in MADRS total score from baseline to week 6 (the primary outcome in the original study, conducted between April 2009 and February 2012).
  
  
  RESULTS
  At baseline, mixed features were present in 56% of patients (lurasidone, n = 182/323; placebo, n = 90/162). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in MADRS scores in the mixed features group (-15.7 vs -10.9; P = .001; week 6; mixed model for repeated measures [MMRM]; effect size, 0.48) and in the group without mixed features (-15.2 vs -10.8; P = .002; week 6; MMRM; effect size, 0.48). Rates of protocol-defined treatment-emergent hypomania or mania were similar for patients with mixed features (lurasidone, 2.2%; placebo, 3.2%) and without mixed features (lurasidone, 3.4%; placebo, 0.0%).
  
  
  CONCLUSIONS
  Lurasidone was found in this post hoc analysis to be efficacious in the treatment of patients with bipolar depression who present with mixed features (assessed cross-sectionally at study baseline). No increased risk of treatment-emergent mania was observed in either group.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00868699.
authors.affiliation: University of Toronto, Departments of Psychiatry and Pharmacology, Mood Disorders Psychopharmacology Unit, 399 Bathurst St, MP 9-325, Toronto, ON, Canada M5T 2S8 roger.mcintyre@uhn.on.ca.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.forename: Josephine
authors.initials: J
authors.lastname: Cucchiaro
authors.forename: Andrei
authors.initials: A
authors.lastname: Pikalov
authors.forename: Hans
authors.initials: H
authors.lastname: Kroger
authors.forename: Antony
authors.initials: A
authors.lastname: Loebel
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D003865:Major Depressive Disorder / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054833:Isoindoles / Q000009:adverse effects / Q000627:therapeutic use*; D000069056:Lurasidone Hydrochloride; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D015203:Reproducibility of Results; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D054833:Isoindoles; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride