Background: There is a need for effective, safe and well-tolerated pharmacotherapies for patients with major depressive disorder (MDD) who have inadequate response to antidepressant treatments (ADTs). This analysis aimed to summarize the short-term efficacy and safety of adjunctive brexpiprazole in adults with MDD. Research design and methods: A pooled analysis of data from the 6-week, randomized, double-blind treatment phases of four studies of adjunctive brexpiprazole 1-3 mg/day versus placebo in outpatients with MDD and inadequate response to ADTs (n = 1,853). Efficacy was measured by Montgomery-Åsberg Depression Rating Scale (MADRS) scores, and safety by treatment-emergent adverse events (TEAEs). Results: ADT + brexpiprazole 2-3 mg/day showed greater improvement in MADRS Total score from baseline to Week 6 than ADT + placebo (least squares mean difference: -2.15; confidence limits: -2.82, -1.48; p < 0.0001; Cohen's d effect size: 0.33). TEAEs with incidence ≥5% with ADT + brexpiprazole 1-3 mg/day were akathisia (8.0% versus 2.6% with ADT + placebo), headache (5.8% versus 6.0%), and weight increased (5.8% versus 1.6%). Conclusions: Adjunctive brexpiprazole is an efficacious and well-tolerated treatment option for adult patients with MDD and inadequate response to ADTs. Study limitations included a lack of active comparator.
Keywords: Adjunctive; antidepressant; brexpiprazole; clinical trial; major depressive disorder.