Cariprazine Augmentation to Antidepressant Therapy in Major Depressive Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Trial

Psychopharmacol Bull. 2018 Jun 20;48(4):62-80.


Cariprazine is an atypical antipsychotic currently under investigation as an adjunctive to antidepressant treatment (ADT) for patients with major depressive disorder (MDD). Here results of an 18- to 19-week randomized double-blind placebo-controlled Phase 3 study evaluating the efficacy of adjunctive cariprazine (1.5-4.5 mg/day[d]) with ADT in participants with previous inadequate response to ADT are presented. ADT response was assessed in an 8-week open-label period; inadequate responders were randomized (N = 530) to open-label ADT plus placebo (n = 261) or cariprazine (n = 269) for the 8-week double-blind phase (NCT01715805). Primary and secondary endpoints were changes at week 8 (cariprazine versus placebo) in Montgomery-Åsberg Depression Rating Scale (MADRS) total score and in Sheehan Disability Scale (SDS) score, respectively, which were analyzed by mixed-effect models for repeated measures. Cariprazine did not significantly improve scores in either compared to placebo, but non-significantly reduced depressive symptoms (MADRS least-squares mean difference [LSMD]: -0.2, P = 0.7948 and SDS LSMD: -0.7, P = 0.2784). Of additional efficacy parameters, cariprazine significantly improved Clinical Global Impressions - Improvement (CGI-I) scores versus placebo (LSMD: -0.2; P = 0.0410). A greater proportion of participants achieved MADRS response with cariprazine vs placebo, but differences were not significant. Cariprazine was generally well-tolerated, and metabolic parameters and body weight changes were not meaningfully different than placebo. Common newly-emergent adverse events included akathisia and restlessness. The lack of significant improvement in depressive symptoms with adjunctive cariprazine and ADT for MDD in inadequate responders contrasts with previously published results, therefore additional studies are needed to understand role of adjunctive cariprazine in MDD.

Keywords: Phase 3; antidepressant agents; antipsychotic agents; cariprazine; clinical trial; depressive disorder; major depressive disorder; randomized-placebo controlled trial; treatment-resistant.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology*
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / pharmacology*
  • Severity of Illness Index


  • Antidepressive Agents
  • Antipsychotic Agents
  • Piperazines
  • cariprazine

Associated data