Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: Results from a post-hoc analysis of two randomised controlled trials

Background: Anxiety symptoms are prevalent in major depressive disorder (MDD) and are associated with greater illness severity, suicidality, impaired functioning and poor response to antidepressant treatment (ADT). The efficacy and safety of brexpiprazole- a serotonin-dopamine activity modulator- as adjunctive treatment in patients with MDD was recently evaluated in two phase 3 studies. We here present a post-hoc analysis of the efficacy of adjunctive brexpiprazole in patients with MDD and symptoms of anxious distress, defined using proxies for DSM-5 criteria. Methods: Eligible patients were randomized to 2 mg brexpiprazole+ADT or placebo+ADT (NC101360645); or 1 mg brexpiprazole+ADT, 3 mg brexpiprazole+ADT, or placebo+ADT (NCf01360632), respectively. Patients were defined as having anxious distress if they had >= 2 of the symptoms tension (MADRS item 3 score >= 3), restlessness (IDS item 24 score >= 2), concentration (MADRS item 6 score >= 3), or apprehension (HAM-D item 10 score >= 3). Primary efficacy endpoint was change in MADRS total score from baseline to Week 6. Results: 55% of the patients had anxious distress at baseline. Adjunctive brexpiprazole showed greater improvement than adjunctive placebo on the primary efficacy endpoint in both patients with (least square mean difference to placebo+ADT: 2 mg+ADT:-2.95, p =0.0023; 3 mg+ADT:-2.81, p=0.0027); and without anxious distress (1 mg+ADT:-2.37, p=0.0093; 3 mg+ADT:-2.23, p=0.0131). Brexpiprazole in patients with anxious distress was not associated with an increased incidence of activating adverse events (e.g., akathisia). Conclusions: Adjunctive brexpiprazole 2-3 mg may be efficacious in reducing depressive symptoms and is well tolerated, in patients with MDD and anxious distress. (C) 2016 Elsevier B.V. All rights reserved.