Among adults with major depressive disorder (MDD) who had an inadequate response to antidepressants alone, adjunctive low-dose cariprazine was found to safely and effectively reduce symptoms of depression. These findings were published in The American Journal of Psychiatry.
This phase 3, randomized, double-blind, placebo-controlled, parallel-group trial was conducted between 2018 and 2021 at 116 sites in the United States, United Kingdom, Bulgaria, Estonia, Germany, Hungary, and Ukraine. Patients (N=757) with MDD with inadequate control of depressive symptoms on antidepressants underwent a 1- to 2-week washout period for additional psychotropic medications but kept taking 1 antidepressant, and were then randomly assigned in a 1:1:1 ratio to receive 1.5 mg daily cariprazine (n=252), 3.0 mg daily cariprazine (n=252), or placebo (n=253) for 6 weeks, and were followed for an additional 4-week safety period. The high-dose cariprazine group was started at 1.5 mg/day for 2 weeks. The primary efficacy outcome was a change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score.
The low- and high-dose cariprazine and placebo cohorts comprised patients aged mean 43.3, 44.8, and 46.4 years; 75.8%, 71.4% and 72.7% were women; 81.3%, 85.3%, and 80.2% were White; 12.7%, 13.1%, and 13.4% had more than 1 antidepressant category failure; and they had a lifetime MDD duration of 12.8, 14.0, and 14.8 years, respectively.
At 6 weeks compared with placebo, 1.5 mg cariprazine was associated with a significant improvement in MADRS score (least squares mean difference [LSMD], -2.5; P =.0025) but 3.0 mg cariprazine dose was not (LSMD, -1.5; P =.0691). Significant improvements in MADRS scores were observed among the 1.5 mg cariprazine group as early as week 2 (P <.05).
Similarly, 1.5 mg cariprazine was significantly favored over placebo for improving Clinical Global Impressions (CGI) severity (LSMD, -0.3; P =.0091), CGI improvement (LSMD, -0.3; P =.0026), the Hamilton Depression Rating Scale (LSMD, -2.1; P =.0014), and the Hamilton Rating Scale for Anxiety (LSMD, -1.3; P =.0370) outcomes at week 6.
Compared with placebo, MADRS response (≥50% reduction) was associated with 1.5 mg cariprazine (odds ratio [OR], 1.5; 95% CI, 1.0-2.1; P =.0446).
The rates of 1 or more treatment-emergent adverse event (TEAE) were 49.6% for 1.5 mg and 49.2% for 3.0 mg cariprazine compared with 36.8% for placebo. One participant in each cariprazine group and 2 in the placebo group had a serious adverse event. Discontinuations due to TEAE occurred among 1.2% of the 1.5 mg cariprazine, 7.1% of the 3.0 cariprazine, and 2.4% of the placebo recipients.
The most common TEAEs in the 1.5 mg cariprazine group were headache (8.7%), nausea (7.9%), and insomnia (7.1%).
The major limitation of this study was the short study duration.
Study authors concluded, “These results suggest that adjunctive cariprazine at 1.5 mg/day is an effective treatment for depressive symptoms in adults with inadequate response to ongoing antidepressant treatment, helping to address an unmet need among patients with MDD.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
This article originally appeared on Psychiatry Advisor
Sachs GS, Yeung PP, Rekeda L, Khan A, Adams JL, Fava M. Adjunctive cariprazine for the treatment of patients with major depressive disorder: a randomized, double-blind, placebo-controlled phase 3 study. Am J Psychiatry. 2023;180(3):241-251. doi:10.1176/appi.ajp.20220504