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

Objective: To evaluate the effects of adjunctive cariprazine on anxiety symptoms in adults with a DSM-5 diagnosis of major depressive disorder (MDD) and inadequate response to antidepressant therapy (ADT).

Methods: In this post hoc analysis of a phase 3 study (NCT03738215), we assessed the effects of adjunctive cariprazine 1.5 and 3.0 mg/d on depressive and anxiety symptoms. The modified intent-to-treat (mITT) population was evaluated, as well as subgroups with varying degrees of baseline anxiety, defined by Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization factor scores and Hamilton Anxiety Rating Scale (HAM-A) total scores. Least squares mean differences (LSMD) in change from baseline to week 6 in Montgomery Asberg Depression Rating Scale and HAM-A total scores and in HAM-D Anxiety/Somatization factor scores were reported.

Results: The mITT population included 751 patients. At week 6, cariprazine 1.5 mg/d +ADT resulted in significantly greater changes in depressive symptoms versus placebo in patients with elevated baseline anxiety (HAM-D Anxiety/Somatization factor subgroup: LSMD [95% CI], -2.4 [-4.2 to -0.7]); HAM A total score subgroup: -2.8 [-4.6 to -1.0]). Adjunctive cariprazine also significantly reduced anxiety symptoms in the overall mITT population, as measured by mean reductions in HAM-D Anxiety/Somatization factor (1.5 mg/d: -0.8 [-1.2 to -0.3]; 3.0 mg/d: -0.5 [-1.0 to -0.1]) and HAM-A total scores (1.5 mg/d: -1.3 [-2.5 to -0.1]). Similar trends were observed for adjunctive cariprazine 1.5 mg/d in subgroups of patients with elevated anxiety symptoms.

Conclusions: In addition to reducing depressive symptoms, adjunctive cariprazine may also reduce anxiety symptoms in patients with MDD, regardless of the level of baseline anxiety.