NCDEU Poster Session 2012

Early and Sustained Response Achieved Across Multiple Measures With Adjunctive Aripiprazole in MDD Patients With an Inadequate Response to Antidepressant Monotherapy

Daniel E. Casey, MD; Kimberly K. Laubmeier, PhD; James M. Eudicone, MS, MBA; Ronald Marcus, MD; Robert M. Berman, MD; Ross A. Baker, PhD, MBA; and John Sheehan, PhD
From the Oregon Health and Science University, Portland (Dr Casey); Otsuka Pharmaceutical Development and Commercialization, Inc, Princeton, New Jersey (Drs Baker and Laubmeier); Bristol-Myers Squibb, Plainsboro, New Jersey (Dr Sheehan and Mr Eudicone); and Bristol-Myers Squibb, Wallingford, Connecticut (Drs Berman and Marcus).

This poster presentation was supported by Bristol-Myers Squibb (Princeton, NJ, USA) and Otsuka Pharmaceutical Co, Ltd (Tokyo, Japan).

Background: Medications with rapid antidepressant effects address an unmet need in major depressive disorder (MDD), as it can take 6–8 weeks to determine if an antidepressant will help a patient. However, a rapid, transient effect will not improve patients’ long-term outcomes. Because of this unmet need, we evaluated the early and sustained antidepressant effects of adjunctive aripiprazole in MDD. Because patients must respond early and at all time points, early and sustained response (ESusR) is a rigorous measure of efficacy. This post-hoc analysis investigated ESusR using measures of symptoms (Montgomery Asberg Depression Rating Scale [MADRS]), total clinical progress from baseline (Clinical Global Impression-Improvement scale [CGI-I]) and clinical state vs. other patients with depression (CGI-Severity scale [CGI-S]).

Methods: In this pooled analysis of three similar studies,1,2 patients had an inadequate response to 1–3 trials of antidepressant therapy (ADT). Each study had an 8-week prospective ADT phase (Phase B), then a 6-week randomized phase of adjunctive aripiprazole vs. adjunctive placebo (Phase C). ESusR was defined as a patient who had a response (≥50% improvement in MADRS total score; CGI-I or CGI-S scores of 1–2 during Phase C) at Week 2 and sustained that response at all subsequent visits (Weeks 3, 4, 5, and 6).

Results: The rate of ESusR by MADRS in the adjunctive aripiprazole group was 11.6% (45/387) vs. 5.4% (21/387) in the adjunctive placebo group (p=0.002; relative risk [RR]=2.2, 95% CI: 1.3, 3.5). Rate of ESusR by CGI-I in the adjunctive aripiprazole group was 30.9% (120/389) vs. 15.3% (59/386) in the adjunctive placebo group (p<0.0001; RR=2.0, 95% CI: 1.5, 2.7). For CGI-S, 13.6% (53/390) and 5.1% (20/389) of adjunctive aripiprazole and placebo patients had an ESusR (p<0.0001); RR=2.6, 95% CI: 1.6, 4.3). The mean weekly ending doses at Week 6 of aripiprazole in those with an ESusR by MADRS, CGI-I and CGI-S, respectively, were 8.5, 9.4 and 8.6 mg/d, compared to presumed doses of 11.8, 11.9 and 12.5 mg/d with adjunctive placebo.

Conclusions: Adjunctive aripiprazole treatment resulted in ESusR more than twice as often as ADT monotherapy using a symptom scale and two global response measures. These results suggest a response cut-off of MADRS improvement ≥50% is a more rigorous response definition than CGI-I 1–2. For all measures, patients who achieved ESusR received an average dose of 5–10 mg/d, reinforcing the recommended dose in MDD.

Learning Objectives:
Demonstrate the efficacy of adjunctive aripiprazole in inducing early and sustained responses in patients with major depressive disorder

Assist clinicians in making earlier treatment decisions for their patients

References
1.  Thase ME, Trivedi MH, Nelson JC, et al. Examining the efficacy of adjunctive aripiprazole in major depressive disorder: a pooled analysis of 2 studies. Prim Care Companion J Clin Psychiatry. 2008;10(6):440–447. PubMed

2.  Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009;14(4):197–206. PubMed

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