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‐HT(1A) and dopamine D(2) receptors at similar potency, and an antagonist at 5‐HT(2A) and noradrenaline alpha(1B/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.