Cariprazine for the Adjunctive Treatment of Major Depressive Disorder in Patients With Inadequate Response to Antidepressant Therapy: Results of a Randomized, Double-Blind, Placebo-Controlled Study

J Clin Psychiatry. 2023 Aug 16;84(5):22m14643. doi: 10.4088/JCP.22m14643.

Abstract

Objective: To assess the efficacy of cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, as adjunctive treatment for patients with major depressive disorder (MDD) and inadequate response to ongoing antidepressant therapy (ADT).

Methods: This randomized, double-blind, placebo-controlled study was conducted from November 2018 to September 2021. Adults with MDD per DSM-5 criteria were randomized (1:1:1) to cariprazine 1.5 mg/d or 3 mg/d plus ADT, or placebo plus ADT. The primary and secondary endpoints were change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score and Clinical Global Impressions-Severity of Illness (CGI-S) score, respectively.

Results: A total of 249 placebo-, 250 cariprazine 1.5 mg/d-, and 251 cariprazine 3 mg/d-treated patients were included in the modified intent-to-treat population. At week 6, the least squares mean change in MADRS total score was -13.8 for cariprazine 1.5 mg/d, -14.8 for cariprazine 3 mg/d, and -13.4 for placebo; differences versus placebo were not statistically significant. Mean change from baseline in CGI-S scores at week 6 was not significant for cariprazine versus placebo, although a trend toward significance was observed for 3 mg/d (P = .0573 [not adjusted for multiplicity]). Common treatment-emergent adverse events (≥ 5% either cariprazine group and twice placebo) were akathisia and insomnia.

Conclusions: There were no statistically significant differences for cariprazine 1.5 or 3 mg/d versus placebo on the primary or secondary outcomes. Cariprazine was generally well tolerated, and no new safety concerns were detected.

Clinical Trials Registration: ClinicalTrials.gov identifier NCT03739203.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / adverse effects
  • Antipsychotic Agents* / therapeutic use
  • Depressive Disorder, Major* / drug therapy
  • Double-Blind Method
  • Humans
  • Treatment Outcome

Substances

  • cariprazine
  • Antipsychotic Agents
  • Antidepressive Agents

Associated data

  • ClinicalTrials.gov/NCT03739203