Efficacy of Adjunctive Cariprazine on Anxiety Symptoms in Patients With Major Depressive Disorder and Baseline Anxiety: Post Hoc Analysis of a Randomized Controlled Trial

Abstract: Background: Adjunctive cariprazine was evaluated in patients with major depressive disorder (MDD) and inadequate response to monotherapy antidepressant treatment (ADT), stratified by baseline anxiety. Methods: Post hoc analysis of a randomized, double-blind, placebo-controlled MDD trial (NCT03738215) of cariprazine+ADT (1.5 or 3 mg/d) versus placebo+ADT evaluated change from baseline to week 6 in Hamilton Anxiety Rating Scale (HAM-A) total score in anxiety subgroups: baseline HAM-A scores >7=at least mild, >14=at least moderate, >23=severe. Least squares mean differences (LSMDs) with 95% confidence intervals (95% CIs) were estimated using a mixed-effects model for repeated measures. Results: The analysis included 751 patients (cariprazine+ADT: 1.5 mg/d=250, 3 mg/d=252; placebo+ADT=249). Baseline anxiety was at least mild for 98.8% of patients, at least moderate for 82.6%, and severe for 34.9%. In the overall population, the LSMD (95% CI) in HAM-A total score change versus placebo+ADT at week 6 was significant for cariprazine 1.5 mg/d+ADT (-1.3 [-2.47, -0.08]; nominal P=0.037), but not for 3 mg/d+ADT (-0.8 [-1.96, 0.46]). In the at least mild and moderate subgroups, the LSMD in HAM-A total score versus placebo+ADT favored cariprazine 1.5 mg/d+ADT (mild=-1.3 [-2.52, -0.10]; moderate=-1.6 [-2.98, -0.23]), but not cariprazine 3 mg/d+ADT (mild=-0.8 [-2.00, 0.43]; moderate=-0.9 [-2.28, 0.52]). In the severe subgroup, the LSMD versus placebo+ADT was -2.0 (-4.7, 0.6) for cariprazine 1.5 mg/d+ADT and -2.3 (-4.9, 0.3) for 3 mg/d+ADT. Conclusions: In this post hoc analysis, adjunctive treatment with cariprazine was associated with reductions in anxiety in patients with MDD regardless of baseline anxiety severity.Short Description: In this post hoc analysis, data from a randomized, controlled clinical trial were used to evaluate cariprazine 1.5 or 3 mg/d plus antidepressant treatment (ADT) versus placebo plus ADT in patients with MDD and inadequate response to ongoing ADT, and baseline anxiety. At week 6, cariprazine plus ADT was associated with improved anxiety across varying levels of baseline anxiety symptoms. These results suggest that adjunctive cariprazine therapy may improve anxiety symptoms in patients with MDD.Name of Sponsoring Organization(s): AbbVie