title: Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants.
abstract: OBJECTIVE
  To assess the efficacy, tolerability, and safety of brexpiprazole as adjunctive therapy to antidepressant treatments (ADTs) in adults with major depressive disorder (as defined by DSM-IV-TR criteria) and inadequate response to ADTs.
  
  
  METHODS
  Patients with historical inadequate response to 1-3 ADTs were enrolled. All patients entered a prospective 8-week phase on physician-determined, open-label ADT. Those with inadequate response were randomized to ADT + brexpiprazole 2 mg/d or ADT + placebo for 6 weeks. The study was conducted between July 2011 and May 2013. The primary efficacy end point was change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The key secondary end point was change from baseline to week 6 in Sheehan Disability Scale (SDS) mean score. The efficacy population comprised all patients who had ≥ 1 dose of study drug in the double-blind phase and both baseline and ≥ 1 postrandomization MADRS scores. The efficacy population per final protocol included patients from the efficacy population who met amended randomization criteria of inadequate response throughout prospective treatment.
  
  
  RESULTS
  Brexpiprazole (n = 175) reduced mean MADRS total score versus placebo (n = 178) at week 6 in the efficacy population per final protocol (-8.36 vs -5.15, P = .0002). Brexpiprazole improved SDS mean score versus placebo (-1.35 vs -0.89, P = .0349). The most common treatment-related adverse events were weight gain (brexpiprazole, 8.0%; placebo, 3.1%) and akathisia (7.4% vs 1.0%).
  
  
  CONCLUSIONS
  Adjunctive brexpiprazole therapy demonstrated efficacy and was well tolerated in patients with major depressive disorder and inadequate response to ADTs.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01360645.
authors: Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, 3535 Market St, Philadelphia, PA 19104 thase@mail.med.upenn.edu.
authors: Michael E
authors: ME
authors: Thase
authors: James M
authors: JM
authors: Youakim
authors: Aleksandar
authors: A
authors: Skuban
authors: Mary
authors: M
authors: Hobart
authors: Carole
authors: C
authors: Augustine
authors: Peter
authors: P
authors: Zhang
authors: Robert D
authors: RD
authors: McQuade
authors: William H
authors: WH
authors: Carson
authors: Margaretta
authors: M
authors: Nyilas
authors: Raymond
authors: R
authors: Sanchez
authors: Hans
authors: H
authors: Eriksson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000009:adverse effects* / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D015363:Quinolones; D013876:Thiophenes; C000591922:brexpiprazole