Full-spectrum efficacy of cariprazine across manic and depressive symptoms of bipolar I disorder in patients experiencing mood episodes: Post hoc analysis of pooled randomized controlled trial data

Introduction: Patients with bipolar I disorder may experience mood destabilization or treatment-emergent affective switch (TEAS) from one symptom pole to the other spontaneously or following treatment. Optimal treatment should address symptoms from both poles without precipitating destabilization. Methods: These were pooled post hoc analyses of data from randomized, double-blind, placebo-controlled studies of cariprazine 3-12 mg/d for bipolar I mania (NCT00488618, NCT01058096, NCT01058668) and cariprazine 1.5 mg/d or 3 mg/d for bipolar I depression (NCT01396447, NCT02670538, NCT02670551). Changes from baseline in Montgomery-& Aring;sberg Depression Rating Scale (MADRS) total score at week 6 and Young Mania Rating Scale (YMRS) total score at week 3 were analyzed in each indication using a mixed-effects model for repeated measures. Percentages of patients with increasing levels of endpoint response and TEAS (bipolar mania = MADRS total score >= 19; bipolar depression = YMRS score >= 16) were determined. Results: Cariprazine significantly reduced manic and depressive symptoms in patients with bipolar I disorder mood episodes. In patients with a manic episode and up to mild baseline depressive symptoms, cariprazine also significantly reduced depressive symptoms. In patients with a depressive episode and manic symptoms in remission at baseline, numerical reduction (without statistical significance) in YMRS indicated no worsening of mania. In both indications, cariprazine-treated patients had numerically greater response rates (presenting symptom pole) than placebo-treated patients; lower percentages of cariprazine- than placebo-treated patients had TEAS at visits where data were collected. Limitations: Post hoc analysis. Conclusion: Results suggested that cariprazine had full-spectrum efficacy across symptoms from both poles in patients with bipolar I disorder mood episodes; TEAS risk was low. Patient-level response suggested that improvement was clinically relevant.