Early improvement with cariprazine as a predictor of antidepressant, anxiolytic, and antimanic response in bipolar I mania and depression: A pooled post hoc analysis of randomized cariprazine trials.

Early symptomatic improvement may predict treatment response in bipolar I disorder. Cariprazine has demonstrated early treatment effects in bipolar I depression and mania studies; therefore, we assessed whether early improvement with cariprazine predicts eventual treatment response. Post hoc analyses used pooled data from randomized, double-blind, placebo-controlled bipolar I depression (NCT02670538 , NCT02670551) and mania (NCT00488618 , NCT01058096 , NCT01058668) trials. In depression studies (cariprazine 1.5 mg/d, 3 mg/d, or placebo), early improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) total scores (≥25 % improvement at day 15) and subsequent depressive/anxiety symptom response status (≥50 % improvement at week 6) were assessed. In mania studies (cariprazine 3–12 mg/d or placebo), early improvement in Young Mania Rating Scale (YMRS) total scores (≥25 % improvement at day 7) and manic symptom response status (≥50 % improvement at week 3) were assessed. Patients with bipolar I depression and early MADRS improvement were approximately 4- to 6-times as likely to achieve MADRS or HAM-A response than those without early improvement; patients with early HAM-A improvement were approximately 3- to 4-times as likely to achieve MADRS or HAM-A response. A subset of patients without early improvement with cariprazine 1.5 mg/d (20 %–31 %) subsequently responded following up-titration. Patients with mania and early YMRS improvement were approximately 5 times more likely to have manic symptom response than those without early improvement. Post hoc analysis; relatively short study durations; flexible-dosing (mania studies). Early symptom improvement with cariprazine may inform therapeutic decisions for patients with bipolar I disorder. • Early improvement with cariprazine predicted week 6 bipolar I depression response. • Early improvement in manic symptoms was also predictive of week 3 mania response. • Some patients without early improvement responded after cariprazine up-titration. [ABSTRACT FROM AUTHOR]