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Original Research

Efficacy and Safety of Adjunctive Cariprazine in Inadequate Responders to Antidepressants: A Randomized, Double-Blind, Placebo-Controlled Study in Adult Patients With Major Depressive Disorder

Suresh Durgam, MD; Willie Earley, MD; Hua Guo,P hD; Dayong Li, PhD; György Németh, MD, PhD; István Laszlovszky, PharmD; Maurizio Fava, MD; and Stuart A. Montgomery, MD, FRCPsych

Published: March 23, 2016

Article Abstract

Background: Cariprazine is an atypical antipsychotic currently under investigation as adjunctive therapy in patients with major depressive disorder (MDD) who have inadequate response to standard antidepressant therapy.

Method: A randomized, double-blind, placebo-controlled, flexible-dose study was conducted from December 2011 to December 2013 in adults who met DSM-IV-TR criteria for MDD and had an inadequate antidepressant response. Eligible patients were randomized to 8-week adjunctive treatment with placebo (n = 269), cariprazine 1-2 mg/d (n = 274), or cariprazine 2-4.5 mg/d (n = 276). The primary efficacy parameter was change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) total score; P values were adjusted for multiple comparisons. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms (ECGs), and suicidality.

Results: Compared with placebo, reduction in MADRS total score at week 8 was significantly greater with adjunctive cariprazine 2-4.5 mg/d (least squares mean difference [LSMD] = -2.2; adjusted P = .0114), but not with cariprazine 1-2 mg/d (LSMD = 0.9; adjusted P = .2404). Significant LSMDs for MADRS total score change were detected at all earlier study visits (weeks 2, 4, 6) in the 2- to 4.5-mg/d group and at weeks 2 and 4 in the 1- to 2-mg/d group (all P values < .05). Treatment-emergent adverse events reported in 10% of patients in either cariprazine dosage group were akathisia (22.3%), insomnia (13.6%), and nausea (12.8%) (all in 2- to 4.5-mg/d group). Mean changes in metabolic parameters, vital signs, and ECG parameters were generally similar between groups. No suicide-related adverse events were reported.

Discussion: These results show that adjunctive cariprazine 2-4.5 mg/d was effective and generally well tolerated in adults with MDD who had inadequate responses to standard antidepressants. Further clinical studies to confirm these results are warranted.

Trial Registration: identifier: NCT01469377

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