Response and Remission Rates With Adjunctive Aripiprazole in Patients With Major Depressive Disorder Who Exhibit Minimal or No Improvement on Antidepressant Monotherapy

D. E. Casey; K. K. Laubmeier; J. M. Eudicone; R. Marcus; R. M. Berman; Z. Rahman; J. Sheehan

Disclosures

Int J Clin Pract. 2014;68(11):1301-1308. 

In This Article

Abstract and Introduction

Abstract

Background The efficacy of adjunctive aripiprazole in patients with major depressive disorder (MDD) with no improvement after 8 weeks of prior antidepressant monotherapy has not been evaluated.

Methods A post hoc analysis of three similarly designed, randomised, double-blind, placebo-controlled, phase III studies was conducted investigating the efficacy and safety of aripiprazole adjunctive to standard antidepressant treatment (ADT) in MDD patients with a prior inadequate response to one to three ADTs. Minimal improvement to antidepressant monotherapy was defined as a Clinical Global Impressions – Improvement (CGI-I) score of 3 and non-improvement as a CGI-I of 4 at weeks 6 and 8 of antidepressant monotherapy.

Results The end-point response rate for ADT minimal improvers receiving adjunctive aripiprazole was 38.8% vs. 26.6% for adjunctive placebo (p < 0.05; number needed to treat [NNT] = 9 [95% confidence interval: 4.8–27.7]), and for ADT non-improvers receiving adjunctive aripiprazole was 24.0% vs. 10.3% for adjunctive placebo (p < 0.05; NNT = 8 [95% confidence interval: 4.4–21.5]). ADT minimal improvers and non-improvers demonstrated significant improvements in response vs. ADT alone as early as after 1 and 2 weeks of adjunctive treatment, respectively. The end-point remission rate for ADT minimal improvers receiving adjunctive aripiprazole was 34.2% vs. 21.0% for adjunctive placebo (p < 0.05; NNT = 8), and for ADT non-improvers receiving adjunctive aripiprazole was 16.0% vs. 5.9% for adjunctive placebo (p < 0.05; NNT = 10). The most common adverse events for ADT minimal improvers and non-improvers receiving adjunctive aripiprazole were akathisia, restlessness and insomnia.

Conclusion Patients with minimal or no improvement after 8 weeks of antidepressant monotherapy significantly benefited from adjunctive aripiprazole treatment, supporting the efficacy of this treatment for MDD patients with all levels of response to ADT.

Introduction

Evidence from the Sequenced Treatment Alternatives to Relieve Depression or STAR*D trial (clinicaltrials.gov: NCT00021528) demonstrated that achieving remission in major depressive disorder (MDD) occurs in a minority of patients early in treatment and becomes more difficult with increasing rounds of treatment.[1] Therefore, with initial treatment, clinicians must weigh the benefit already achieved and the probability of remission with continued treatment against the probability of reaching remission and the potential side effect burden, associated with undertaking the next treatment step.[1] Specifically, clinicians must decide when remission is sufficiently unlikely and subsequent alternative treatments should be considered.

Treatment practice guidelines published by the American Psychiatric Association outline a variety of treatment options for patients with minimal and partial response to antidepressant treatment (ADT), including augmentation with a second agent.[2–4] Traditionally, augmentation has been employed for patients with MDD exhibiting partial response to ADT, while for patients with a minimal response to ADT, switching between agents is commonly preferred. A recent analysis, however, has shown that aripiprazole augmentation is a meaningful treatment option for patients with a minimal response to ADT [< 25% reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) total score], as well as for patients with a partial response to ADT (25–50% reduction in MADRS total score).[5] Notwithstanding this finding, clinicians will often switch medications rather than augment patients who do not show at least a partial response to ADT (e.g. > 25% reduction in MADRS total score).[2] It remains to be determined, however, whether adjunctive aripiprazole can result in significant and rapid benefits in patients who had no improvement with ADT.

This post hoc analysis used the Clinical Global Impressions–Improvement (CGI-I) scale to assess clinically relevant global response to treatment; specifically, whether adjunctive aripiprazole could provide benefits for patients who had no improvement with antidepressant monotherapy. As measurement-based care becomes more relevant in clinical practice, information about the use of a simple and practical scale, such as the CGI-I, that is both valid and reliable[6,7] is important. Response and remission rates were evaluated for patients receiving adjunctive aripiprazole treatment after exhibiting minimal or no improvement with 8 weeks of antidepressant monotherapy. Data were pooled from three similarly designed studies of aripiprazole augmentation of ADT in patients with MDD.[8–10] Minimal improvement to antidepressant monotherapy was defined as a CGI-I score of 3 and non-improvement was defined as a CGI-I score of 4 at weeks 6 and 8 of antidepressant monotherapy.

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