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

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

Methods: Data were pooled from three international, randomized, double-blind, placebo-controlled, Phase 3 trials. Adult outpatients with MDD and inadequate response to antidepressant treatments were enrolled. Patients were stratified post hoc into minimal and partial response subgroups based on their response over an 8-week prospective antidepressant treatment period. Adjunctive brexpiprazole 2-3 mg/day (versus adjunctive placebo) was investigated in a 6-week randomized treatment period. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions - Severity of illness (CGI-S). 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: 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). Significance Statement Depression is a common mental disorder associated with a constant feeling of sadness or lack of interest in daily life. Treatment with antidepressant medication can help to improve symptoms of depression. However, the amount of improvement varies from person to person. For people who still have symptoms on antidepressants, one option is to add brexpiprazole. Brexpiprazole is a medication that can help to improve symptoms of depression when taken with an antidepressant. Our study used data from clinical trials to look at the effects of brexpiprazole in people with either "minimal" or "partial" improvement on antidepressant. We found that, in both groups, people who added brexpiprazole had a greater improvement in symptoms than people who added a placebo (dummy drug). This means that adding brexpiprazole may help people with depression regardless of the amount of improvement they had on antidepressant alone.

Keywords: clinical trials; depression; subgroup analysis; treatment augmentation; treatment optimization.