An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine in Patients With Bipolar I Depression.

Abstract

OBJECTIVE:

The authors evaluated the efficacy, safety, and tolerability of cariprazine, an atypical antipsychotic candidate, in adult patients with acute bipolar I depression.

METHOD:

This was an 8-week multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in adult patients with bipolar I disorder experiencing a current major depressive episode. Patients were randomly assigned (1:1:1:1) to receive placebo or cariprazine at 0.75, 1.5, or 3.0 mg/day. The primary and secondary efficacy parameters were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions severity subscale (CGI-S), respectively, analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population.

RESULTS:

The intent-to-treat population comprised 571 patients (141 in the placebo group and 140, 145, and 145 in the cariprazine 0.75-, 1.5-, and 3.0-mg/day groups). Cariprazine at 1.5 mg/day showed significantly greater improvement on MADRS total score change from baseline to week 6 compared with placebo; the least squares mean difference was -4.0 (95% CI=-6.3, -1.6; significant after adjustment for multiple comparisons). Cariprazine at 3.0 mg/day showed greater MADRS score reduction than placebo (-2.5, 95% CI=-4.9, -0.1; not significant when adjusted for multiple comparisons). The 0.75 mg/day dosage was similar to placebo. A similar pattern for significance was observed on the CGI-S (1.5 mg/day: least squares mean difference=-0.4, 95% CI=-0.6, -0.1; 3.0 mg/day: -0.3, 95% CI=-0.5, -0.0). The most common adverse events (≥10%) in cariprazine-treated patients were akathisia and insomnia; weight gain was slightly higher with cariprazine than with placebo.

CONCLUSIONS:

Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated, suggesting efficacy for the treatment of bipolar I depression.

• Authors: Suresh Durgam, Willie Earley, Alan Lipschitz, Hua Guo, István Laszlovszky, György Németh, Eduard Vieta, Joseph R Calabrese, Lakshmi N Yatham
• Journal: The American journal of psychiatry (Am J Psychiatry) Vol. 173 Issue 3 Pg. 271-81 (Mar 01 2016) ISSN: 1535-7228 [Electronic] United States
• PMID: 26541814 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Piperazines
• cariprazine

Topics

• Adult
• Antipsychotic Agents (administration & dosage, adverse effects)
• Bipolar Disorder (diagnosis, drug therapy, psychology)
• Depression (diagnosis, drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Monitoring
• Female
• Humans
• Male
• Middle Aged
• Piperazines (administration & dosage, adverse effects)
• Psychiatric Status Rating Scales
• Treatment Outcome