title: Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy.
abstract: BACKGROUND
  Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT).
  
  
  METHODS
  This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery-Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10.
  
  
  RESULTS
  Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo).
  
  
  CONCLUSIONS
  These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.
authors.affiliation: 1Department of Psychiatry,University of California,San Francisco,California,USA.
authors.forename: J Craig
authors.initials: JC
authors.lastname: Nelson
authors.affiliation: 2Medical Affairs Neuroscience Department,Bristol-Myers Squibb,Plainsboro,New Jersey,USA.
authors.forename: Zia
authors.initials: Z
authors.lastname: Rahman
authors.affiliation: 3Field Medical Affairs Department,Otsuka America Pharmaceutical,Inc.,Princeton,New Jersey,USA.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Laubmeier
authors.affiliation: 4Global Biometric Sciences Department,Bristol-Myers Squibb,Plainsboro,New Jersey,USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Eudicone
authors.affiliation: 5Global Medical,Regulatory Affairs and Alliances,Otsuka Pharmaceutical Development & Commercialization,Inc.,Princeton,New Jersey,USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: McQuade
authors.affiliation: 6Global Clinical Research Neuroscience,Bristol-Myers Squibb,Wallingford,Connecticut,USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Berman
authors.affiliation: 7NS Global Clinical Research,Bristol-Myers Squibb,Wallingford,Connecticut,USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Marcus
authors.affiliation: 8CNS Global Medical Affairs,Otsuka Pharmaceutical Development & Commercialization,Inc.,Princeton,New Jersey,USA.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Baker
authors.affiliation: 9Medical Affairs Neuroscience Department,Bristol-Myers Squibb,Plainsboro,New Jersey,USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sheehan
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole