title: Adjunctive brexpiprazole in patients with major depressive disorder and anxiety symptoms: an exploratory study.
abstract: Major depressive disorder (MDD) with concurrent anxiety symptoms may signal a difficult-to-treat patient. Brexpiprazole is a serotonin-dopamine activity modulator: a partial agonist at 5-HT1Aand dopamine D2receptors at similar potency, and an antagonist at 5-HT2Aand noradrenaline alpha1B/2Creceptors. The objective of this Phase IIIb study was to explore effectiveness, safety, and tolerability of brexpiprazole adjunctive to antidepressant (ADT) monotherapy in patients with MDD and anxiety symptoms (NCT02013531).
  
  
  
  Patients with MDD, Hamilton Anxiety Rating Scale (HAM-A) total score ≥ 20, and inadequate response to current ADT received open-label brexpiprazole 1-3 mg day-1(target dose 2 mg day-1) + ADT for 6 weeks. Efficacy endpoints included change from baseline at Week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, HAM-A total score, and Sheehan Disability Scale (SDS). Safety and tolerability assessments included adverse events (AEs).
  
  
  
  Of 37 participants enrolled, 32 (86.5%) completed the study. Baseline mean (SD) MADRS total score was 30.1 (5.1); mean HAM-A total score was 26.9 (5.0). Improvements from baseline were observed at Week 6 for least squares mean change in MADRS total score (-19.6,p< .0001 vs. baseline), HAM-A total score (-17.8,p< .0001) and mean (SD) SDS mean score [-3.6 (2.6)]. Brexpiprazole was well tolerated. The most frequent treatment-emergent AEs were increased appetite (13.5%) and diarrhea, dry mouth, and dizziness (all 10.8%).
  
  
  
  These open-label results support the anxiolytic effects of adjunctive brexpiprazole in the treatment of patients with MDD.
authors: Veterans Affairs Medical Center Tuscaloosa AL USA; University of Alabama School of Medicine Birmingham AL USA.
authors: Lori L
authors: LL
authors: Davis
authors: Otsuka Pharmaceutical Co., Ltd. Tokyo Japan.
authors: Ai
authors: A
authors: Ota
authors: Otsuka Pharmaceutical Development & Commercialization, Inc. Princeton NJ USA.
authors: Pamela
authors: P
authors: Perry
authors: Otsuka Pharmaceutical Co., Ltd. Tokyo Japan.
authors: Kana
authors: K
authors: Tsuneyoshi
authors: H. Lundbeck A/S Valby Denmark.
authors: Emmanuelle
authors: E
authors: Weiller
authors: Otsuka Pharmaceutical Development & Commercialization, Inc. Princeton NJ USA.
authors: Ross A
authors: RA
authors: Baker
mesh_terms: D001007:Anxiety / Q000150:complications* / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000150:complications* / Q000188:drug therapy*; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D018490:Serotonin Agents / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists; D011619:Psychotropic Drugs; D015363:Quinolones; D018490:Serotonin Agents; D013876:Thiophenes; C000591922:brexpiprazole
keywords: antidepressant treatments; anxiety; clinical trials; depression; mood disorders