Adjunctive brexpiprazole in patients with major depressive disorder and anxiety symptoms: an exploratory study.

Background: Major depressive disorder (MDD) with concurrent anxiety symptoms may signal a difficult-to-treat patient. Brexpiprazole is a serotonin-dopamine activity modulator: a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors. The objective of this Phase IIIb study was to explore effectiveness, safety, and tolerability of brexpiprazole adjunctive to antidepressant (ADT) monotherapy in patients with MDD and anxiety symptoms (NCT02013531).

Methods: Patients with MDD, Hamilton Anxiety Rating Scale (HAM-A) total score ≥ 20, and inadequate response to current ADT received open-label brexpiprazole 1-3 mg day-1 (target dose 2 mg day-1) + ADT for 6 weeks. Efficacy endpoints included change from baseline at Week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, HAM-A total score, and Sheehan Disability Scale (SDS). Safety and tolerability assessments included adverse events (AEs).

Results: Of 37 participants enrolled, 32 (86.5%) completed the study. Baseline mean (SD) MADRS total score was 30.1 (5.1); mean HAM-A total score was 26.9 (5.0). Improvements from baseline were observed at Week 6 for least squares mean change in MADRS total score (-19.6, p < .0001 vs. baseline), HAM-A total score (-17.8, p < .0001) and mean (SD) SDS mean score [-3.6 (2.6)]. Brexpiprazole was well tolerated. The most frequent treatment-emergent AEs were increased appetite (13.5%) and diarrhea, dry mouth, and dizziness (all 10.8%).

Conclusions: These open-label results support the anxiolytic effects of adjunctive brexpiprazole in the treatment of patients with MDD.