Effects of Adjunctive Brexpiprazole on Individual Depressive Symptoms and Functioning in Patients With Major Depressive Disorder and Anxious Distress: Post Hoc Analysis of Three Placebo-Controlled Studies.

Purpose/background: Anxiety symptoms in major depressive disorder (MDD) are frequent, and they decrease response to antidepressant treatment (ADT), and affect patient functioning. This post hoc analysis examined the efficacy of adjunctive brexpiprazole on individual depressive symptoms and functioning in patients with MDD with anxious distress.

Methods/procedures: Data were included from three 6-week, randomized, double-blind, placebo-controlled studies of adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (ClinicalTrials.gov identifiers: NCT01360645, NCT01360632, NCT02196506). Patients were stratified using proxy criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, anxious distress. Changes in Montgomery-Åsberg Depression Rating Scale item scores and Sheehan Disability Scale mean score from baseline to week 6 were determined for ADT + brexpiprazole (2 and 2-3 mg) versus ADT + placebo.

Findings/results: At baseline, 450 of 746 patients (60.3%, 2 mg analysis) and 670 of 1162 patients (57.7%, 2-3 mg analysis) had anxious distress. In patients with anxious distress, ADT + brexpiprazole 2 mg or 2 to 3 mg showed greater improvements than ADT + placebo (P < 0.05) on the Montgomery-Åsberg Depression Rating Scale items of apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, lassitude, inability to feel, and pessimistic thoughts (Cohen d effect sizes, 0.18-0.44), and on Sheehan Disability Scale mean score (effect sizes, 0.21-0.23).

Implications/conclusions: Adjunctive brexpiprazole is efficacious in reducing core depressive symptoms, sleep, and appetite, as well as improving functioning, in patients with MDD and anxious distress who have inadequate response to ADTs.