title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ClinicalTrials.gov identifier: NCT01469377.
authors.affiliation: Forest Research Institute, Clinical Development, Harborside Financial Center, Jersey City, NJ 07311 suresh.durgam@actavis.com.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
authors.forename: Willie
authors.initials: W
authors.lastname: Earley
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.forename: Dayong
authors.initials: D
authors.lastname: Li
authors.forename: György
authors.initials: G
authors.lastname: Németh
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Montgomery
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance / Q000187:drug effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine