title: Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants.
abstract: BACKGROUND
  Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.
  
  
  METHODS
  Patients (N=1,147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2-20 mg/day). Primary outcome was the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).
  
  
  RESULTS
  Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (-10.1) than placebo (-6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).
  
  
  CONCLUSIONS
  For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196).
authors.affiliation: Neuroscience Global Clinical Research at Bristol-Myers Squibb, Wallingford, CT 06492, USA. Robert.Berman@bms.com
authors.forename: Robert M
authors.initials: RM
authors.lastname: Berman
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: René
authors.initials: R
authors.lastname: Swanink
authors.forename: Robert D
authors.initials: RD
authors.lastname: McQuade
authors.forename: William H
authors.initials: WH
authors.lastname: Carson
authors.forename: David
authors.initials: D
authors.lastname: Adson
authors.forename: Leslie
authors.initials: L
authors.lastname: Taylor
authors.forename: James
authors.initials: J
authors.lastname: Hazel
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Marcus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004351:Drug Resistance; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole