Efficacy of adjunctive brexpiprazole on the core symptoms of major depressive disorder: A post hoc analysis of two pooled clinical studies

Background: Patients with major depressive disorder (MDD) who do not adequately respond to antidepressant treatment (ADT) may benefit from adjunctive atypical antipsychotics; however, certain agents target specific symptoms of depression and not the full syndrome. The aim of this analysis was to examine the effects of brexpiprazole, adjunct to ADT, on the core symptoms of MDD, defined using Montgomery-Asberg Depression Rating Scale (MADRS) items. Methods: This was a post hoc analysis of data from two 6-week, randomized, double-blind studies of adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (n = 1056). Efficacy was assessed using the MADRS core symptom subscale (MADRS(6)) and individual items (apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts). Results: At Week 6, adjunctive brexpiprazole showed a greater effect than adjunctive placebo on the MADRS6 (within-group Cohen's d effect sizes: brexpiprazole, 1.05; placebo, 0.71; p < 0.001 between groups) and on each of the six core symptoms (effect sizes: brexpiprazole, 0.64-0.94; placebo, 0.39-0.64; all p < 0.001). At Week 2, adjunctive brexpiprazole already showed a greater effect than adjunctive placebo on the MADRS6, and on five of the core symptoms (all p < 0.01). Limitations: This was a post hoc analysis of studies that were not designed for this purpose. Correction for multiple comparisons was not performed. Conclusions: Brexpiprazole, as adjunct to ADT, produced a statistically significant and clinically meaningful improvement on the core symptoms of MDD. Brexpiprazole is thought to exert its effects in MDD by treating the core symptoms of the disease.