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

George I Papakostas,1 Prakash S Masand,2 Anita H Clayton,3 Vladimir Maletic4 ,† Julie L Adams,5 Ludmyla Rekeda,6 Manpreet Kaur Singh,7 Majid Kerolous8 1Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; 2Academic Medicine Education Institute, Duke-NUS, Singapore, Singapore; 3Department of Psychiatry & Neurobehavioral Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA; 4Department of Psychiatry and Behavioral Science, University of South Carolina School of Medicine, Greenville, SC, USA; 5Global Development, Psychiatry, AbbVie, North Chicago, IL, USA; 6Biostatistics, AbbVie, North Chicago, IL, USA; 7Department of Psychiatry and Behavioral Sciences, UC Davis Medical Center, Sacramento, CA, USA; 8Neuroscience Clinical Development, AbbVie, North Chicago, IL, USA†Dr. Vladimir Maletic passed away on December 11, 2024Correspondence: Majid Kerolous, Neuroscience Clinical Development, AbbVie, 1 N. Waukegan Road, North Chicago, IL, 60064, USA, Tel + 1 862 261 7425, Email [email protected]: 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.Keywords: cariprazine, atypical antipsychotics, major depressive disorder, post hoc analysis, full range of efficacy