title: Adjunctive Brexpiprazole in Patients With Major Depressive Disorder and Irritability: An Exploratory Study.
abstract: OBJECTIVE
  To evaluate the effects of adjunctive brexpiprazole on symptoms of irritability in patients with major depressive disorder (MDD).
  
  
  METHODS
  Patients diagnosed with MDD according to DSM-IV-TR criteria who had inadequate response to antidepressant treatment continued treatment with their current antidepressant for 2 weeks. Patients still having inadequate response, and with irritability, received 6 weeks of open-label treatment with their current antidepressant at the same dose and adjunctive brexpiprazole (target dose: 3 mg/d). Brexpiprazole was discontinued at week 6, and the patients continued with their antidepressant until week 10. Changes from baseline to week 6 and week 6 to week 10 were analyzed.
  
  
  RESULTS
  This study was conducted between October 7, 2013, and July 30, 2014. Fifty-four patients were treated with adjunctive brexpiprazole. At week 6, clinically relevant improvements were observed in Sheehan Irritability Scale total (-21.1) and item 1 (irritable mood) (-3.5) scores, Kellner Symptom Questionnaire total (-24.4) and anger-hostility subscale (-7.7) scores, and 30-item Inventory of Depressive Symptomatology, clinician version (IDS-C₃₀), item 6 (irritable mood) score (-1.2). More (15 patients) stopped than developed (5 patients) anger attacks during treatment, as measured by the Anger Attacks Questionnaire. The Clinical Global Impressions-Severity of Illness score improved (-1.4), as did the depressive symptoms (IDS-C₃₀ total score, -17.8; Kellner Symptom Questionnaire depression subscale score, -7.7; and Montgomery-Asberg Depression Rating Scale total score, -14.2). Irritability symptoms worsened after brexpiprazole discontinuation, assessed at week 10. Adjunctive brexpiprazole was well tolerated.
  
  
  CONCLUSIONS
  Adjunctive treatment with brexpiprazole may represent a strategy for patients with MDD and inadequate response to antidepressant treatment who have symptoms of irritability.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01942785.
authors.affiliation: Massachusetts General Hospital, 55 Fruit St, Bulfinch 351, Boston, MA 02114. mfava@mgh.harvard.edu.|Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: François
authors.initials: F
authors.lastname: Ménard
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Charlotte Kampp
authors.initials: CK
authors.lastname: Davidsen
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Baker
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018490:Serotonin Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D015363:Quinolones; D018490:Serotonin Agents; D013876:Thiophenes; C000591922:brexpiprazole