Background: Brexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2c receptors.
Objectives: To evaluate efficacy outcomes of adjunctive treatment with brexpiprazole vs placebo in patients with MDD who demonstrated inadequate response to antidepressant treatment (ADT). Methods: This trial (NCT01360645) had 3 phases: screening (7-28 days); prospective 8-week, single-blind placebo plus an investigator-determined, open-label ADT; randomized: 6-week, double-blind, adjunctive brexpiprazole (2mg/day) vs placebo in patients with an inadequate response to ADT. Efficacy was measured using the MADRS total score, the SDS, the CGI-S, HAM-D 17, CGI-I and HAM-A scores. Changes from randomization to week 6 in efficacy scales were analyzed using a mixed model repeated measures analysis.
Results: In the 379 patients randomized, change in MADRS showed a 3.1 point treatment effect on efficacy population (P<0.001) and 3.2 on the amended efficacy population (P<0.001). Similar statistically robust findings were observed on the mean SDS, and the SDS family life subscale score. Secondary efficacy measures confirmed the effect of adjunctive brexpiprazole on reducing depressive symptoms. Responder rate was greater for adjunctive brexpiprazole subjects compared to subjects receiving placebo+ADT on both MADRS (23.5% vs 14.7%, P<0.05) and CGI improvement scales (44.4% vs 27.7%, P<0.001). A difference between adjunctive brexpiprazole and placebo+ADT was also observed on change in HAM-A total score (-3.94 vs -2.77, P<0.05).
Conclusions: In addition to clinical benefits on depressive symptoms, adjunctive brexpiprazole improved social functioning in patients with MDD who demonstrated inadequate response to ADT.