Objective: To summarize efficacy data from two phase 2 and two phase 3 short-term,
multicenter, randomized, double-blind, placebo-controlled studies of brexpiprazole adjunctive to
antidepressant treatments (ADTs) in patients with major depressive disorder (MDD) with inadequate
response to ADTs.
Methods: Patients with MDD who were inadequate responders to 1–3 prior ADTs entered an 8-week
single-blind prospective treatment phase on physician-determined ADT. Patients with inadequate
response throughout the prospective treatment phase were randomized to receive either placebo or
brexpiprazole (phase 2: flexible dosage 0.15–3.0 mg/day; phase 3: fixed-dosages 1, 2, or 3 mg/day) as
adjunctive treatment to their ADT. The primary endpoint was change in Montgomery-Åsberg Depression
Rating Scale (MADRS) total score from baseline to week 6.
Results: Phase 2 studies suggested brexpiprazole doses of 1–3 mg/day were effective as an adjunctive
therapy. These observations were confirmed across the two phase 3 studies utilizing a pooled placebo
group versus brexpiprazole 1, 2, and 3 mg/day and a pooled analysis of all four studies (brexpiprazole 1–3
mg/day). Greater improvements were observed in MADRS total score with brexpiprazole+ADT versus
placebo+ADT (1 mg/day, p<0.01; 2 mg/day, p<0.01; 3 mg/day, p<0.001; brexpiprazole 1–3 mg/day,
Conclusion: Adjunctive brexpiprazole is an efficacious treatment option for patients with MDD and
inadequate response to ADT.
ClinicalTrials.gov: NCT00797966; NCT01052077; NCT01360632; NCT01360645.