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

Int J Neuropsychopharmacol. 2025 Aug 1;28(8):pyaf050. doi: 10.1093/ijnp/pyaf050.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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

Keywords: antidepressant; brexpiprazole; depression; disease course; treatment optimization.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents* / administration & dosage
  • Antidepressive Agents* / adverse effects
  • Antidepressive Agents* / therapeutic use
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Major Depressive Disorder* / drug therapy
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Quinolones* / administration & dosage
  • Quinolones* / adverse effects
  • Quinolones* / pharmacology
  • Quinolones* / therapeutic use
  • Randomized Controlled Trials as Topic
  • Thiophenes* / administration & dosage
  • Thiophenes* / adverse effects
  • Thiophenes* / pharmacology
  • Thiophenes* / therapeutic use
  • Treatment Outcome

Substances

  • brexpiprazole
  • Thiophenes
  • Quinolones
  • Antidepressive Agents

Associated data

  • ClinicalTrials.gov/NCT01360645
  • ClinicalTrials.gov/NCT01360632
  • ClinicalTrials.gov/NCT02196506