Early Improvement With Cariprazine as a Predictor of Antidepressant and Anxiolytic Response in Bipolar Depression: Pooled Post Hoc Analysis of 2 Randomized Cariprazine Trials

Abstract: Introduction: Treatment non-response may indicate need for further clinical management; thus, early prediction of treatment response can aid clinical decision-making, including dose titration. This analysis evaluated whether early antidepressant/anxiolytic improvement with cariprazine predicted later treatment response. Methods: Pooled data from 2 randomized, double-blind, clinical trials (NCT02670538, NCT02670551; Nf981) of cariprazine 1.5 or 3.0 mg/d versus placebo in patients with bipolar I depression were analyzed. Cariprazine was initiated at 1.5 mg/d; patients in the 3.0 mg/d group were uptitrated on Day 15. The optimal predictive value threshold for early improvement was identified as ≥25% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) or Hamilton Anxiety Rating Scale (HAMA) total score at Week 2. Treatment response was defined as ≥50% reduction in MADRS/HAMA total score at Week 6. Odds ratios (OR) and positive predictive values (PPV) associated with early improvement were calculated. Results: A greater proportion of cariprazine- versus placebo-treated patients met criteria for MADRS early improvement (1.5 mg/d=49.1%; 3.0 mg/d=52.7%; placebo=42.9%). Among early improvers, 69% of patients in the 1.5 and 3.0 mg/d groups met criteria for MADRS response (1.5 mg/d: OR=8.6, PPV=69.0%; 3.0 mg/d: OR=7.8, PPV=69.5%) and 64% (OR=5.5; PPV=63.9%) and 60% (OR=5.7; PPV=59.9%) met HAMA response, respectively. Predictive results were generally similar based on HAMA early improvement. Among patients without early improvement, 21–32% achieved MADRS or HAMA response following uptitration to cariprazine 3.0 mg/d. Conclusion: While early improvement with cariprazine robustly predicted later treatment response, continuation of treatment and dose uptitration may also benefit patients without early improvement.Short Description: In this pooled post hoc analysis of 2 randomized trials of cariprazine 1.5 or 3.0 mg/d versus placebo in patients with bipolar I depression, early (Week 2) improvement of depression/anxiety symptoms with cariprazine predicted later (Week 6) antidepressant and anxiolytic responses. Some patients without early improvement responded when the cariprazine dose was increased to 3.0 mg/d. These results suggest that early improvement with cariprazine may predict later antidepressant and anxiolytic response in bipolar I depression.Name of Sponsoring Organization(s): AbbVie