Research paperTolerability of cariprazine in the treatment of acute bipolar I mania: A pooled post hoc analysis of 3 phase II/III studies

•Post hoc safety analyses assessed cariprazine in patients with bipolar I disorder.•The FDA-recommended dose range for patients with bipolar mania is 3-6 mg/d.•Cariprazine was generally safe and well-tolerated within the recommended dose range.

BackgroundAtypical antipsychotics have broad-spectrum efficacy against core symptoms of acute mania/mixed states in bipolar disorder; however, they are associated with clinically significant adverse effects (AEs).MethodsThis post hoc analysis evaluated the safety and tolerability of the atypical antipsychotic cariprazine in the treatment of adult patients with acute manic/mixed episodes of bipolar I disorder. Data were taken from three 3-week randomized, double-blind, placebo-controlled, flexible-dose trials of cariprazine 3-12 mg/d. Patient subgroups categorized by modal daily dose (3-6 mg/d; 9-12 mg/d) were used to assess dose response.ResultsThe pooled safety population comprised 1065 patients (placebo=442; cariprazine 3-6 mg/d=263; cariprazine 9-12 mg/d=360). More cariprazine- than placebo-treated patients reported double-blind treatment-emergent AEs; the overall AE incidence was similar among cariprazine-dose groups. AEs reported in ≥5% of cariprazine patients overall with at least twice the incidence of placebo were akathisia, extrapyramidal symptoms, restlessness, and vomiting. The incidence of SAEs was low and similar between the placebo- and cariprazine-treatment groups. Metabolic parameter changes were small and generally similar between cariprazine and placebo groups; mean increases in fasting glucose levels were greater with cariprazine (3-6mg/d=6.6 mg/dL; 9-12 mg/d=7.2 mg/dL) than placebo (1.7 mg/dL). Mean weight change was 0.54 kg and 0.17 kg for cariprazine and placebo, respectively; weight increase ≥7% was <3% in all treatment groups. Cariprazine was not associated with clinically meaningful changes in electrocardiogram parameters.LimitationsPost hoc analysis, flexible-dose design, short trial duration.ConclusionCariprazine was generally safe and well-tolerated in patients with manic/mixed episodes associated with bipolar I disorder.