Efficacy and Clinical Relevance of Adjunctive Cariprazine Treatment in Patients with Major Depressive Disorder: Post Hoc Analyses from a Phase III Study.

Objective: Efficacy analyses that go beyond the primary outcome of major depressive disorder (MDD) clinical trials and consider clinical relevance, response range, disease severity, and patient subpopulations may inform clinical decision-making. This post hoc analysis assessed clinically relevant outcomes associated with adjunctive cariprazine for MDD. Methods: Data from a randomized controlled trial (NCT03738215) of cariprazine 1.5 or 3 mg/d + antidepressant therapy (ADT) versus placebo + ADT were analyzed. Change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed and number of patients achieving thresholds of MADRS response (≥5, ≥10, ≥15, ≥20, and ≥25 points) were determined. MADRS severity shifts were reported as the proportion of patients with no change or worsened severity, 1, ≥1, and ≥2 category improvements. Other efficacy characterizations included improvements in each MADRS item score and MADRS total score improvement across demographic-defined (age, sex, race) patient subgroups, baseline ADT response, and number of prior ADTs. Results: More patients treated with adjunctive cariprazine versus placebo had MADRS total score improvements across all response thresholds and achieved ≥1 MADRS severity category improvement. Adjunctive cariprazine was associated with numerically greater improvements versus placebo in all individual MADRS items, with statistically significant improvements in 7/10 items. Adjunctive cariprazine was also associated with MADRS total score reductions, regardless of patient demographics, baseline ADT response, or number of prior ADTs. Conclusion: Results suggest that adjunctive cariprazine provides clinically meaningful improvements in depressive symptoms, with efficacy ranging across individual depressive symptoms and in diverse subpopulations.