Cariprazine is an antipsychotic medication and received approval by the U.S. 
Food and Drug Administration for the treatment of schizophrenia in September 
2015. Cariprazine is a dopamine D3 and D2 receptor partial agonist, with a 
preference for the D3 receptor. Cariprazine is also a partial agonist at the 
serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A 
receptors. The recommended dose range of cariprazine for the treatment of 
schizophrenia is 1.5-6 mg/d; the starting dose of 1.5 mg/d is potentially 
therapeutic. Cariprazine is administered once daily and is primarily metabolized 
in the liver through the CYP3A4 enzyme system and, to a lesser extent, by 
CYP2D6. There are two active metabolites of note, desmethyl-cariprazine and 
didesmethyl-cariprazine; the latter's half-life is substantially longer than 
that for cariprazine and systemic exposure to didesmethyl-cariprazine is several 
times higher than that for cariprazine. Three positive, 6-week, Phase 2/3, 
randomized controlled trials in acute schizophrenia demonstrated superiority of 
cariprazine over placebo. Pooled responder rates were 31% for cariprazine 1.5-6 
mg/d vs. 21% for placebo, resulting in a number needed to treat (NNT) of 10. In 
a 26-72 week, randomized withdrawal study, significantly fewer patients relapsed 
in the cariprazine group compared with placebo (24.8% vs. 47.5%), resulting in 
an NNT of 5. The most commonly encountered adverse events (incidence ≥5% and at 
least twice the rate of placebo) are extrapyramidal symptoms (number needed to 
harm [NNH] 15 for cariprazine 1.5-3 mg/d vs. placebo and NNH 10 for 4.5-6 mg/d 
vs. placebo) and akathisia (NNH 20 for 1.5-3 mg/d vs. placebo and NNH 12 for 
4.5-6 mg/d vs. placebo). Short-term weight gain appears small (approximately 8% 
of patients receiving cariprazine 1.5-6 mg/d gained ≥7% body weight from 
baseline, compared with 5% for those randomized to placebo, resulting in an NNH 
of 34). Cariprazine is associated with no clinically meaningful alterations in 
metabolic variables, prolactin, or the ECG QT interval. Cariprazine is also 
approved for the acute treatment of manic or mixed episodes associated with 
bipolar I disorder. Clinical trials are ongoing in patients with acute bipolar I 
depression and as adjunctive treatment to antidepressant therapy in patients 
with major depressive disorder.