Efficacy of dose increase among nonresponders to low-dose aripiprazole augmentation in patients with inadequate response to antidepressant treatment: a randomized, double-blind, placebo-controlled, efficacy trial.
Author(s): Mischoulon D, Witte J, Levy M, Papakostas GI, Pet LR, Hsieh WH, Pencina MJ, Ward S, Pollack MH, Fava M
Affiliation(s): 1 Bowdoin Sq, 6th Floor, Massachusetts General Hospital, Boston, MA 02114, USA. firstname.lastname@example.org.
Publication date & source: 2011-09-20, J Clin Psychiatry., [Epub ahead of print]
OBJECTIVE: To examine the efficacy of a dose increase of aripiprazole to 5 mg/d in subjects with major depressive disorder (MDD) who did not respond to 4 weeks of treatment with aripiprazole 2 mg/d in a randomized, double-blind, placebo-controlled, parent study. METHOD: 221 Subjects with Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition-diagnosed DSM-IV-TR MDD (mean +/- SD age, 45 +/- 11 years; 64% women) with inadequate antidepressant response were recruited from September 2008-July 2009 and randomized to 60 days of double-blind augmentation with either aripiprazole or placebo in two 30-day phases. The study was performed across 8 academic hospital sites and 14 nonacademic (private clinic) sites throughout the United States. Randomization in a 2:3:3 ratio per sequential parallel comparison design was drug/drug (aripiprazole 2 mg/d in phase 1 and 5 mg/d in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1 and aripiprazole 2 mg/d in phase 2). In phase 2, we examined efficacy of an aripiprazole dose increase to 5 mg/d in nonresponders to 2 mg/d by assessing response rates (>/= 50% reduction in Montgomery-Asberg Depression Rating Scale [MADRS] score [primary outcome measure]) and score changes in MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, 9-item Patient Health Questionnaire (PHQ-9), the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, and patient-rated versions of the CGI-I and CGI-S scales. RESULTS: Response rate for aripiprazole 2 mg/d in phase 1 was 18.5% (n/n = 10/54). Among 39 nonresponders who increased their dose to 5 mg/d, response rate was 12.8% (95% CI, 4.30%-27.43%), with significant overall mean +/- SD reductions in MADRS scores (-9.46 +/- 7.83 [95% CI, -12.00 to -6.92]; P < .0001), Symptoms Questionnaire Distress scores (19.51 +/- 17.73 [95% CI, 13.60 to 25.43]; P < .0001), PHQ-9 scores (-7.92 +/- 5.92 [95% CI, -9.89 to -5.94]; P < .0001), and CGI-S scores (-0.86 +/- 0.86 [95% CI, -1.15 to -0.58]; P < .0001). Differences in efficacy between drug and placebo groups were nonsignificant, however. Aripiprazole and placebo were well tolerated. CONCLUSIONS: Augmentation with aripiprazole 5 mg/d may provide only a modest additional benefit in patients who do not benefit from lower doses. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00683852. (c) Copyright 2011 Physicians Postgraduate Press, Inc.