Adjunctive Brexpiprazole in Patients With Major Depressive Disorder and Irritability: An Exploratory Study.

Fava, Maurizio; Ménard, François; Davidsen, Charlotte Kampp; Baker, Ross A

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. TRIALS REGISTRATION ClinicalTrials.gov identifier: NCT01942785.