OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic 
with preferential binding to D3 receptors, is approved for the treatment of 
schizophrenia and manic or mixed episodes associated with bipolar I disorder. 
The efficacy and safety of cariprazine was established in three randomized, 
double-blind, placebo-controlled, 6-week trials in patients with acute 
exacerbation of schizophrenia. This 53-week study evaluated the long-term safety 
and tolerability of cariprazine in patients with schizophrenia.
METHODS: This was a multicenter, open-label, flexible-dose study of cariprazine 
3-9 mg/d in adults with schizophrenia. Participants included new patients and 
patients who had completed one of two phase III lead-in studies (NCT01104766, 
NCT01104779). Eligible patients entered a no-drug screening period of up to 1 
week followed by 48 weeks of flexibly dosed, open-label cariprazine treatment 
(3-9 mg/d) and 4 weeks of safety follow-up.
RESULTS: A total of 586 patients received open-label cariprazine treatment, ~39% 
of whom completed the study. No unexpected safety issues or deaths were 
reported. The most common (≥10%) adverse events (AEs) observed were akathisia 
(16%), headache (13%), insomnia (13%), and weight gain (10%). Serious AEs 
occurred in 59 (10.1%) patients, and 73 (12.5%) patients discontinued the study 
due to AEs during open-label treatment. Mean changes in metabolic, hepatic, and 
cardiovascular parameters were not considered clinically relevant. Mean body 
weight increased by 1.5 kg during the study, prolactin levels decreased 
slightly, and measures of efficacy remained stable.
CONCLUSIONS: Long-term cariprazine treatment at doses up to 9 mg/d appeared to 
be generally safe and well tolerated in patients with schizophrenia.