Full Range of Clinical Improvement in Depression Symptoms With Adjunctive Cariprazine Treatment in Patients With Major Depressive Disorder: Results From a Randomized Phase 3 Clinical Trial

Abstract: Background: Clinical trial results often report mean changes, though individual responses may be more valuable in clinical practice. This analysis explored the ability of adjunctive cariprazine to produce a range of improvements in depressive symptoms in patients with major depressive disorder (MDD) and inadequate response to antidepressant monotherapy (ADT). Methods: Data from a randomized controlled MDD trial (NCT03738215) of cariprazine 1.5 or 3 mg/d + ADT versus placebo + ADT were analyzed. Improvement in depressive symptoms was evaluated by change from baseline to week 6 in Montgomery–Åsberg Depression Rating Scale (MADRS) total scores; patients achieving increasing levels of MADRS response (≥5, ≥10, ≥15, ≥20, and ≥25 points) was determined; missing data was imputed using LOCF. Results: There were 751 patients in the analysis (1.5 mg/d=250, 3.0 mg/d=252; placebo=249). Mean MADRS total score change from baseline was significantly different versus placebo (-11.5) for cariprazine 1.5 mg/d (-14.1; adjusted P=.0050), but not cariprazine 3 mg/d (-13.1). In post hoc analysis, a greater proportion of patients receiving cariprazine + ADT versus placebo + ADT improved ≥5 points (1.5 mg/d and 3.0 mg/d=84%; placebo=74%), ≥10 points (1.5 mg/d=64%; 3.0 mg/d=66%; placebo=54%), and ≥15 points (1.5 mg/d=46%; 3.0 mg/d=43%; placebo=35%). More cariprazine 1.5 mg/d patients versus placebo patients improved ≥20 points (1.5 mg/d=33%; 3.0 mg/d=24%; placebo=23%) and ≥25 points (1.5 mg/d=19%; 3.0 mg/d=11%; placebo=12%). Conclusions: Adjunctive cariprazine produced a range of patient-specific reductions in MADRS total score that were generally greater than placebo, suggesting that mean changes may not reflect individual patient response.Short Description: This post hoc analysis evaluated the efficacy of adjunctive cariprazine + ADT treatment compared with placebo + ADT across the full range of clinical benefits on MADRS total score in MDD patients with inadequate response to monotherapy ADT. Treatment with cariprazine was associated with greater individual improvement in depressive symptoms than placebo at various response levels. These data may provide clinically important patient-specific efficacy information for the adjunctive use of cariprazine in patients with MDD.Name of Sponsoring Organization(s): AbbVie