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-Åsberg 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.