Safety and Tolerability of Cariprazine for the Adjunctive Treatment of Major Depressive Disorder: A Pooled Analysis of Phase 2B and 3 Clinical Trials

Abstract: Background: Safety of cariprazine in patients with major depressive disorder (MDD) with inadequate response to antidepressants was evaluated. Methods: Safety, tolerability, and efficacy of cariprazine as adjunctive treatment for patients with MDD with inadequate response to antidepressant alone was assessed in 5 placebo-controlled studies (two 6-week fixed-dose studies; three 8-week flexible-dose studies) and one 26-week open-label flexible-dose study. Fixed doses (1.5 and 3 mg/d) and flexible doses (0.1-4.5 mg/d) of cariprazine were evaluated. Safety assessments included adverse-event (AE) reporting, clinical laboratory tests, weight/vital signs, and suicide evaluation with Columbia-Suicide Severity Rating Scale (C-SSRS). Pooled analyses of safety endpoints incidence performed using frequently used (modal) daily-dose taken during the study. Results: 2,222 MDD patients with ongoing antidepressant treatment with cariprazine, representing 370 patient-years of exposure in placebo-controlled and open-label studies. In placebo-controlled studies: 1,969 patients randomized to cariprazine (dose range, 0.1-4.5 mg/d); 1,108 patients randomized to placebo. Treatment-emergent AEs occurred in 61% of cariprazine- and 48% of placebo-treated patients; discontinuation from AE occurred with 6% of cariprazine- and 2% of placebo-treated patients. Akathisia (cariprazine=11%; placebo=2%) and restlessness (cariprazine=6%; placebo=2%) occurred in at least 5% of cariprazine-treated patients, at a rate at least twice that of placebo-treated patients. In long-term safety study, mean weight change was 1.6 kg over 6-months. Other safety endpoints were consistent with cariprazine safety profile in bipolar disorder and schizophrenia indications. Conclusion: Cariprazine is safe and well-tolerated in MDD patients with inadequate response to antidepressant monotherapy; no new safety signals. Data is consistent with currently approved prescribing information.Short Description: Cariprazine was assessed as an adjunctive treatment in adults with MDD who otherwise responded inadequately to antidepressant monotherapy using data from six placebo-controlled studies. Cariprazine was safe and well-tolerated, no new safety signals were observed, and the data is consistent with the currently approved prescribing information.Name of Sponsoring Organization(s): AbbVie