Adjunctive Aripiprazole Doubles the Rate of Early and Sustained Response 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).
Objective: The goal of treating major depressive disorder (MDD) is sustained remission of symptoms,1 ideally beginning early in the course of therapy. However, antidepressant therapy (ADT) often requires 6–8 weeks to determine if it has reached its intended effect, and this delay may impede the successful clinical use of ADT. This post-hoc analysis investigated if the effect of adjunctive aripiprazole on early and sustained response (ESusR) compared with ADT alone. ESusR is a particularly rigorous efficacy measure because patients must respond early (at Week 2) and at all subsequent time points.
Methods: Data from three similar studies were pooled.1,2 All patients had to have an inadequate response to 1–3 trials of ADT. Each study included an 8-week prospective ADT phase (Phase B), followed by a 6-week randomized phase of adjunctive aripiprazole versus adjunctive placebo (Phase C). ESusR was defined as a patient who had a response (≥50% improvement in Montgomery Asberg Depression Rating Scale [MADRS] total score during Phase C) to treatment at Week 2 and sustained that response at all subsequent visits (Weeks 3, 4, 5, and 6) among patients who attended all visits.
Results: : The rate of ESusR in the adjunctive aripiprazole group was 11.6% (45/387) versus 5.4% (21/387) in the adjunctive placebo group (P=0.002; odds ratio [OR]=2.3, 95% CI: 1.3, 3.9). Out of the overall population, 22.7% (88/387) of adjunctive-aripiprazole treated patients and 10.9% (42/387) of adjunctive-placebo recipients responded at Week 2. Of those who had an early response, 51.1% (45/88) of patients in the adjunctive aripiprazole group and 50.0% (21/42) of patients in the adjunctive placebo group attained ESusR (P=0.904). Among patients who achieved ESusR on adjunctive aripiprazole, the most common adverse events were akathisia (20.0%), restlessness (17.8%), fatigue (13.3%), insomnia (13.3%), and blurred vision (11.1%), which are similar to the general aripiprazole population.1,2 The mean weekly ending dose of aripiprazole in those who achieved ESusR was 8.5 mg/day, compared with 11.8 mg with adjunctive placebo.
Conclusions: Adjunctive aripiprazole treatment produced ESusR more than twice as often as ADT monotherapy. The early onset of adjunctive aripiprazole efficacy may be clinically valuable as it allows for earlier identification of response leading to better patient management.
Demonstrate the efficacy of adjunctive aripiprazole in inducing early and sustained response using a measure of symptoms in patients with major depressive disorder
Assist clinicians in making earlier treatment decisions for their patients
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