BACKGROUND: Atypical 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).
METHODS: This 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 3-12mg/d. Patient subgroups categorized by modal daily dose 
(3-6mg/d; 9-12mg/d) were used to assess dose response.
RESULTS: The pooled safety population comprised 1065 patients (placebo=442; 
cariprazine 3-6mg/d=263; cariprazine 9-12mg/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=6.6mg/dL; 
9-12mg/d=7.2mg/dL) than placebo (1.7mg/dL). Mean weight change was 0.54kg and 
0.17kg 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.
LIMITATIONS: Post hoc analysis, flexible-dose design, short trial duration.
CONCLUSION: Cariprazine was generally safe and well-tolerated in patients with 
manic/mixed episodes associated with bipolar I disorder.