Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: Results from a post-hoc analysis of two randomised controlled trials

J Affect Disord. 2016 Sep 1;201:116-23. doi: 10.1016/j.jad.2016.05.013. Epub 2016 May 12.


Background: Anxiety symptoms are prevalent in major depressive disorder (MDD) and are associated with greater illness severity, suicidality, impaired functioning and poor response to antidepressant treatment (ADT). The efficacy and safety of brexpiprazole - a serotonin-dopamine activity modulator - as adjunctive treatment in patients with MDD was recently evaluated in two phase 3 studies. We here present a post-hoc analysis of the efficacy of adjunctive brexpiprazole in patients with MDD and symptoms of anxious distress, defined using proxies for DSM-5 criteria.

Methods: Eligible patients were randomized to 2mg brexpiprazole+ADT or placebo+ADT (NCT01360645); or 1mg brexpiprazole+ADT, 3mg brexpiprazole+ADT, or placebo+ADT (NCT01360632), respectively. Patients were defined as having anxious distress if they had ≥2 of the symptoms tension (MADRS item 3 score ≥3), restlessness (IDS item 24 score ≥2), concentration (MADRS item 6 score ≥3), or apprehension (HAM-D item 10 score ≥3). Primary efficacy endpoint was change in MADRS total score from baseline to Week 6.

Results: 55% of the patients had anxious distress at baseline. Adjunctive brexpiprazole showed greater improvement than adjunctive placebo on the primary efficacy endpoint in both patients with (least square mean difference to placebo+ADT: 2mg+ADT: -2.95, p=0.0023; 3mg+ADT: -2.81, p=0.0027); and without anxious distress (1mg+ADT: -2.37, p=0.0093; 3mg+ADT: -2.23, p=0.0131). Brexpiprazole in patients with anxious distress was not associated with an increased incidence of activating adverse events (e.g., akathisia).

Conclusions: Adjunctive brexpiprazole 2-3mg may be efficacious in reducing depressive symptoms and is well tolerated, in patients with MDD and anxious distress.

Keywords: Adjunctive treatment; Anxious distress; Brexpiprazole; Major depressive disorder.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / physiopathology
  • Depression
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Dopamine Agonists / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychomotor Agitation / drug therapy
  • Psychomotor Agitation / physiopathology
  • Quinolones / therapeutic use*
  • Serotonin Agents / therapeutic use*
  • Thiophenes / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents
  • Dopamine Agonists
  • Quinolones
  • Serotonin Agents
  • Thiophenes
  • brexpiprazole

Associated data