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)

Clinical Trials and Network Institute (CTNI), Massachusetts General Hospital, Boston, MA 02114, USA.
Psychotherapy and Psychosomatics (Impact Factor: 9.2). 02/2012; 81(2):87-97. DOI: 10.1159/000332050
Source: PubMed


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.
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.
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.
This study provides clear support for the tolerability of low-dose aripiprazole as an ADT-augmenting agent, with marginal efficacy.

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    • "arable to those with AC or SW . Moreover , augmentation did not cause significantly greater weight gain . These results may be attributable to the lower aripiprazole dose used in our study than in the three RCTs ( Berman et al . , 2009 , 2007 ; Marcus et al . , 2008 ) . The tolerability of low - dose AT has also been demonstrated in a recent RCT ( Fava et al . , 2012 ) . Our study has several strengths . First , this is the first patient preference - based study comparing the effectiveness and tolera - bility among three treatment strategies to overcome partial or non - response to current antidepressants carried out in routine practice . Moreover , the uniformly Korean population is another strengt"
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