Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study

Abstract

Objective: To assess the efficacy, safety, and tolerability of brexpiprazole as adjunctive treatment in adults with major depressive disorder (MDD) and an inadequate response to prior antidepressant treatment (ADT).

Methods: Patients with a current major depressive episode after prior treatment with 1−3 ADTs entered an 8- or 10-week prospective treatment phase in which they received double-blind placebo adjunct to open-label ADT. Inadequate responders were randomized (2:2:1) to brexpiprazole 2−3 mg/day, placebo, or quetiapine extended-release (XR) 150−300 mg/day, adjunct to the same ADT, for 6 weeks. The primary efficacy endpoint was the change from baseline (randomization) to week 6 in Montgomery−Åsberg Depression Rating Scale (MADRS) total score. The key secondary efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score.

Results: Adjunctive brexpiprazole showed a greater improvement in MADRS total score than adjunctive placebo (least squares mean difference [95% confidence interval] = −1.48 [−2.56, −0.39]; p = .0078), whereas adjunctive quetiapine XR did not separate from placebo (−0.30 [−1.63, 1.04]; p = .66). Adjunctive brexpiprazole failed to separate from placebo on the SDS mean score (−0.23 [−0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items (family life and social life). The most frequent treatment-emergent adverse events in patients receiving brexpiprazole were akathisia (6.1%), somnolence (5.6%), and headache (5.6%).

Conclusions: Adjunctive brexpiprazole 2−3 mg/day improved symptoms of depression compared with adjunctive placebo in patients with MDD and an inadequate response to ADTs, and was well tolerated with no unexpected side effects.

Keywords:

• Brexpiprazole
• major depressive disorder
• adjunctive
• antidepressant
• clinical trial

Notes

Transparency

Declaration of funding

This study was supported by Otsuka Pharmaceutical Development & Commercialization Inc. (Princeton, US) and H. Lundbeck A/S (Valby, Denmark). The sponsors were responsible for the study design and conduct; the collection, management, analysis, and interpretation of the data; and the writing and reviewing of this article.

Declaration of financial/other relationships

M.H., A.S., P.Z., C.A., C.B., R.S., and R.D.M. have disclosed that they are full-time employees of Otsuka Pharmaceutical Development & Commercialization Inc. M.K.J. and N.H. have disclosed that they are full-time employees of H. Lundbeck A/S. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

Writing support was provided by Chris Watling, PhD, assisted by his colleagues at Cambridge Medical Communication Ltd (Cambridge, UK), and funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S.

All authors contributed towards data analysis/interpretation, drafting and revising the paper, and agree to be accountable for all aspects of the work.

Notes

^aPatients were randomly assigned to an 8- or 10-week prospective treatment phase (compared with an 8-week prospective treatment phase in previous adjunctive brexpiprazole studies) to further blind the timing of randomization.

^bWhich was achieved, compared with previous studies^7,8.