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.
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