Adjunctive brexpiprazole in patients with major depressive disorder who show minimal or partial response to antidepressant treatment: post hoc analysis of randomized controlled trials.

Abstract

Importance: Many patients with major depressive disorder (MDD) have <50% symptom reduction on antidepressant treatment, and may benefit from an adjunctive atypical antipsychotic.

Objective: To investigate the efficacy and safety of adjunctive brexpiprazole in patients with minimal (>0% to <25%) and partial (≥25 to <50%) response to antidepressant treatment.

Design: Data were pooled from three international, 6-week, randomized, double-blind, placebo-controlled, Phase 3 trials.

Setting: Outpatient.

Participants: Adults with MDD and inadequate response to antidepressant treatments. Patients were stratified into minimal and partial response subgroups based on their response over an 8-week prospective antidepressant treatment period.

Interventions: Adjunctive brexpiprazole 2-3 mg/day or adjunctive placebo.

Main outcomes and measures: Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions - Severity of illness (CGI-S) in the 6-week randomized adjunctive treatment period. Safety was assessed by treatment-emergent adverse events (TEAEs).

Results: In patients with minimal response to antidepressant treatment (n = 663), least squares (LS) mean (SE) MADRS total score change over the randomized treatment period was -8.8 (0.3) points for antidepressant + brexpiprazole and -6.3 (0.3) points for antidepressant + placebo; the LS mean difference at Week 6 was -2.47 (95% CI, -3.38 to -1.55); p<.001; Cohen's d, 0.41. In patients with partial response to antidepressant treatment (n = 235), corresponding changes were -6.4 (0.5) and -4.9 (0.5) points; LS mean difference, -1.53 (-2.94 to -0.11); p=.035; Cohen's d, 0.28. CGI-S results aligned with MADRS results. In patients with minimal response to antidepressant treatment, the incidence of TEAEs was 196/328 (59.8%) for antidepressant + brexpiprazole and 160/335 (47.8%) for antidepressant + placebo. In patients with partial response to antidepressant treatment, corresponding values were 63/115 (54.8%) and 49/120 (40.8%).

Conclusions and relevance: Adjunctive brexpiprazole may be efficacious in MDD regardless of whether patients show minimal or partial response to antidepressant treatment.

Trial registration: Post hoc analysis of NCT01360645, NCT01360632, NCT02196506 (ClinicalTrials.gov).