# Adjunctive brexpiprazole in patients with unresolved symptoms of depression on antidepressant treatment who are early in the disease course: post hoc analysis of randomized controlled trials

## TL;DR

Adding brexpiprazole to antidepressants helps reduce depression symptoms in patients both early and late in their disease course.

## Contribution

Shows brexpiprazole is effective regardless of how long a patient has had depression.

## Key findings

- Brexpiprazole improved MADRS scores more than placebo in both early and late disease subgroups.
- Adverse events were common but similar across subgroups for brexpiprazole and placebo.
- Earlier treatment with brexpiprazole may offer greater benefits for patients and healthcare systems.

## Abstract

Treatment for major depressive disorder (MDD) should be optimized as early as possible in the disease course to minimize patient suffering and maximize clinical benefits. This post hoc analysis aimed to investigate the efficacy and safety of adjunctive brexpiprazole in patients who were earlier and later in the disease course.

Data were pooled from three 6-week, randomized, double-blind, placebo-controlled trials of adjunctive brexpiprazole in adult outpatients with MDD and inadequate response to antidepressant treatment. “Earlier” and “later” disease course subgroups were defined based on the proxies of median age, age at diagnosis, number of episodes, episode duration, and number of prior antidepressants. Efficacy was assessed by changes in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, and safety by treatment-emergent adverse events.

Greater improvement in MADRS total score at week 6 (P < .05) was observed for antidepressant + brexpiprazole 2–3 mg/day (n = 579) versus antidepressant + placebo (n = 583) in all subgroups representing earlier and later disease course, with treatment effects (least-squares mean differences in score change) ranging from −1.79 to −2.92 points. The incidence of treatment-emergent adverse events across subgroups was 53.1%–67.2% for antidepressant + brexpiprazole 2–3 mg/day and 43.0%–51.8% for antidepressant + placebo, with no consistent differences in patients who were earlier or later in the disease course.

Adjunctive brexpiprazole improved depressive symptoms earlier in the disease course, when benefits to patients and healthcare systems can be maximized. Adjunctive brexpiprazole also improved depressive symptoms later in the disease course; there was no advantage of delaying brexpiprazole treatment.

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