Efficacy of adjunctive cariprazine across individual depressive symptoms in major depressive disorder: a post-hoc analysis

Abstract: Background: Patients with major depressive disorder (MDD) who have inadequate response to antidepressant treatment (ADT) may require adjunctive therapy. Cariprazine (CAR), a dopamine D3 preferring D3/D2 and serotonin 5HT1A receptor partial agonist, was evaluated as an adjunctive MDD treatment. Methods: The primary endpoint in this post-hoc analysis assessed the efficacy of CAR across a range of depressive symptoms by evaluating individual items of the Montgomery-Asberg Depression Rating Scale (MADRS) in outpatients from a phase 3 study from baseline to 6 weeks; pooled data from CAR 1.5 mg/d + ADT and CAR 3.0 mg/d + ADT vs placebo (PBO) + ADT were compared (NCT03738215). Results: Based on 751 patients (CAR 1.5 mg/d + CAR 3.0 mg/d = 502, PBO = 249), the LSMD (95% CI) for MADRS individual item score change from baseline to Week 6 was significant in favor of CAR vs PBO for “apparent sadness” (-0.2 [-0.44, -0.03], P = 0.0247), “reported sadness” (-0.4 [-0.58, -0.16], P = 0.0006), “reduced appetite” (-0.3 [-0.50, -0.10], P = 0.0036), “lassitude” (-0.3 [-0.56, -0.12], P = 0.0025), “inability to feel” (-0.3 [-0.51, -0.06, P = 0.0126), “pessimistic thoughts” (-0.3 [-0.45, -0.07], P = 0.0088), and “suicidal thoughts” (-0.1 [-0.20,-0.02], P = 0.0127). AEs were consistent with the established CAR safety profile. Conclusions: In patients with MDD and an inadequate response to ADT alone, adjunctive treatment with CAR produced significantly greater improvement across multiple MADRS individual depressive symptoms compared to PBO.Short Description: In 751 patients with major depressive disorder, cariprazine efficacy (1.5 mg/day and 3.0 mg/day) vs placebo (in addition to antidepressant therapy for all groups) was evaluated for 6 weeks by individually assessing items of the MADRS scale (examining a range of depressive symptoms). Cariprazine showed significant favor in “apparent sadness”, “reported sadness”, “reduced appetite”, “lassitude”, “inability to feel”, “pessimistic thoughts”, and “suicidal thoughts”. Adverse events were consistent with the established cariprazine safety profile.Name of Sponsoring Organization(s): AbbVie, Inc.