title: A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy among depressed outpatients with inadequate response to prior antidepressant therapy (ADAPT-A Study).
abstract: BACKGROUND
  We assessed the efficacy of low-dose aripiprazole added to antidepressant therapy (ADT) in major depressive disorder (MDD) patients with inadequate response to prior ADT.
  
  
  METHODS
  As per the sequential parallel comparison design, 225 MDD subjects were randomized to adjunctive treatment with aripiprazole 2 mg/day or placebo across two 30-day phases, with a 2:3:3 randomization ratio to drug/drug (aripiprazole 2 mg/day in phase 1; 5 mg/day in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1; aripiprazole 2 mg/day in phase 2). Eligible subjects were patients whose MDD was independently deemed 'valid' with SAFER criteria. Subjects had been receiving ADT for ≥8 weeks, and had inadequate response to ≥1 and <4 adequate ADTs in the current episode, as defined by the Antidepressant Treatment Response Questionnaire.
  
  
  RESULTS
  The pooled, weighted response difference between aripiprazole 2 mg/day and placebo in the two phases was 5.6% (p = 0.18; NS). The aripiprazole 2 mg/day-placebo difference on the Montgomery-Asberg Depression Rating Scale pooled across the two phases was -1.51 (p = 0.065; NS). Other secondary endpoint analyses showed nonsignificant pooled differences favoring aripiprazole over placebo. Of the 225 randomized subjects in phase 1, 2 dropped out in both arms, while in phase 2, of 138 phase 1 placebo nonresponders, 9 dropped out on aripiprazole and 5 on placebo. There were only minimal differences in adverse event rates between treatments, except for constipation, weight gain, and dry mouth, more common on aripiprazole.
  
  
  CONCLUSIONS
  This study provides clear support for the tolerability of low-dose aripiprazole as an ADT-augmenting agent, with marginal efficacy.
authors.affiliation: Clinical Trials and Network Institute (CTNI), Massachusetts General Hospital, Boston, MA 02114, USA. MFava@partners.org
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: David
authors.initials: D
authors.lastname: Mischoulon
authors.forename: Dan
authors.initials: D
authors.lastname: Iosifescu
authors.forename: Janet
authors.initials: J
authors.lastname: Witte
authors.forename: Michael
authors.initials: M
authors.lastname: Pencina
authors.forename: Martina
authors.initials: M
authors.lastname: Flynn
authors.forename: Linda
authors.initials: L
authors.lastname: Harper
authors.forename: Michael
authors.initials: M
authors.lastname: Levy
authors.forename: Karl
authors.initials: K
authors.lastname: Rickels
authors.forename: Mark
authors.initials: M
authors.lastname: Pollack
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D003248:Constipation / Q000139:chemically induced; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D000068180:Aripiprazole; D010879:Piperazines; D010919:Placebos; D015363:Quinolones; D017367:Selective Serotonin Reuptake Inhibitors