To evaluate the efficacy of adjunctive aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive aripiprazole to ADT in patients with major depressive disorder who had a minimal response [<25% reduction on the Montgomery–Åsberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ≤10. Rates were examined using analysis of covariance and Cochran–Mantel–Haenszel tests. Kaplan–Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (−10.3 vs. −6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.
aUniversity of California, San Francisco, California
bUniversity of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
cBristol-Myers Squibb, Plainsboro, New Jersey
dBristol-Myers Squibb, Wallingford, Connecticut
eOtsuka Pharmaceutical Development and Commercialization Inc., Princeton, New Jersey, USA
Previous presentations: ACNP 2009 Annual meeting, 6–9 December, Hollywood, Florida, USA. Poster 77; APA 2010 Annual meeting, 22–26 May, San Diego, California, USA; NCDEU 2010 Annual meeting, 14–17 June, Boca Raton, Florida, USA; ECNP 2010 Annual meeting, 30 August–1 September, Amsterdam, The Netherlands.
Clinical trial registration: a study of adjunctive aripiprazole in patients with major depressive disorder. ID numbers: NCT00095823, NCT00095758 and NCT00105196. Registry: www.clinicaltrials.gov
Correspondence to James Craig Nelson, MD, Department of Psychiatry, University of California San Francisco, 401 Parnassus Ave, San Francisco, CA 94143, USA Tel: +1 415 476 7405; fax: +1 415 476 7320; e-mail: CraigN@lppi.ucsf.edu
Received October 18, 2011
Accepted December 7, 2011