Cariprazine is an atypical antipsychotic currently under investigation as an adjunctive to antidepressant treatment (ADT) for patients with major depressive disorder (MDD). Here results of an 18- to 19-week randomized double-blind placebo-controlled Phase 3 study evaluating the efficacy of adjunctive cariprazine (1.5-4.5 mg/day[d]) with ADT in participants with previous inadequate response to ADT are presented. ADT response was assessed in an 8-week open-label period; inadequate responders were randomized (N = 530) to open-label ADT plus placebo (n = 261) or cariprazine (n = 269) for the 8-week double-blind phase (NCT01715805). Primary and secondary endpoints were changes at week 8 (cariprazine versus placebo) in Montgomery-Åsberg Depression Rating Scale (MADRS) total score and in Sheehan Disability Scale (SDS) score, respectively, which were analyzed by mixed-effect models for repeated measures. Cariprazine did not significantly improve scores in either compared to placebo, but non-significantly reduced depressive symptoms (MADRS least-squares mean difference [LSMD]: -0.2, P = 0.7948 and SDS LSMD: -0.7, P = 0.2784). Of additional efficacy parameters, cariprazine significantly improved Clinical Global Impressions - Improvement (CGI-I) scores versus placebo (LSMD: -0.2; P = 0.0410). A greater proportion of participants achieved MADRS response with cariprazine vs placebo, but differences were not significant. Cariprazine was generally well-tolerated, and metabolic parameters and body weight changes were not meaningfully different than placebo. Common newly-emergent adverse events included akathisia and restlessness. The lack of significant improvement in depressive symptoms with adjunctive cariprazine and ADT for MDD in inadequate responders contrasts with previously published results, therefore additional studies are needed to understand role of adjunctive cariprazine in MDD.
Keywords: Phase 3; antidepressant agents; antipsychotic agents; cariprazine; clinical trial; depressive disorder; major depressive disorder; randomized-placebo controlled trial; treatment-resistant.