title: Remission and recovery associated with lurasidone in the treatment of major depressive disorder with subthreshold hypomanic symptoms (mixed features): post-hoc analysis of a randomized, placebo-controlled study with longer-term extension.
abstract: OBJECTIVE
  This post-hoc analysis assessed rates of symptomatic and functional remission, as well as recovery (combination of symptomatic and functional remission), in patients treated with lurasidone for major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features).
  
  
  METHODS
  Patients with MDD plus two or three manic symptoms (defined as per the DSM-5 mixed-features specifier) were randomly assigned to flexible-dose lurasidone 20-60 mg/day (n=109) or placebo (n=100) for 6 weeks, followed by a 3-month open-label, flexible-dose extension study for U.S. sites only (n=48). Cross-sectional recovery was defined as the presence of both symptomatic remission (Montgomery-Åsberg Depression Rating Scale score ≤ 12) and functional remission (all Sheehan Disability Scale [SDS] domain scores ≤3) at week 6, and at both months 1 and 3 of the extension study ("sustained recovery").
  
  
  RESULTS
  A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed cross-sectionally) compared to placebo (12.2%, p=0.002) at week 6. The number of manic symptoms at baseline moderated the effect size for attaining cross-sectional recovery for lurasidone treatment (vs. placebo) (p=0.028). Sustained recovery rates were higher in patients initially treated with lurasidone (20.8%) versus placebo (12.5%).
  
  
  CONCLUSIONS
  In this post-hoc analysis of a placebo-controlled study with open-label extension that involved patients with MDD and mixed features, lurasidone was found to significantly improve the rate of recovery at 6 weeks (vs. placebo) that was sustained at month 3 of the extension study. The presence of two (as opposed to three) manic symptoms moderated recovery at the acute study endpoint.
authors.affiliation: 1Icahn School of Medicine at Mount Sinai,New York,New York,USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Goldberg
authors.affiliation: 2Global Health Economics and Outcomes Research,Sunovion Pharmaceuticals Inc.,Marlborough,Massachusetts,USA.
authors.forename: Daisy
authors.initials: D
authors.lastname: Ng-Mak
authors.affiliation: 3COS and Associates Ltd.,Central,Hong Kong,People's Republic of China.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Siu
authors.affiliation: 2Global Health Economics and Outcomes Research,Sunovion Pharmaceuticals Inc.,Marlborough,Massachusetts,USA.
authors.forename: Chien-Chia
authors.initials: CC
authors.lastname: Chuang
authors.affiliation: 2Global Health Economics and Outcomes Research,Sunovion Pharmaceuticals Inc.,Marlborough,Massachusetts,USA.
authors.forename: Krithika
authors.initials: K
authors.lastname: Rajagopalan
authors.affiliation: 4Research and Development,Sunovion Pharmaceuticals Inc.,Fort Lee,New Jersey,USA.
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; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008134:Long-Term Care; 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; functional remission combined symptomatic and functional remission; lurasidone; mixed features