Cariprazine
Vraylar
Second-Generation Antipsychotic (Partial D2/D3 Agonist)Generic availableTDM data
The mechanism of action of cariprazine is unknown. However, the efficacy of cariprazine could be mediated through a combination of partial agonist activity at central dopamine D 2 and serotonin 5-HT 1A receptors and antagonist activity at serotonin 5-HT 2A receptors. Cariprazine forms two major metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR), that have in vitro receptor binding profiles similar to the parent drug.
Compare Cariprazine →FDA-Approved Indications
- Schizophrenia (adults; adolescents 13+)
- Acute manic or mixed episodes in Bipolar I (adults; pediatric 10+)
- Bipolar I depression (adults)
- MDD — adjunct to antidepressants (adults)
Common Off-Label Uses
- Treatment-resistant depression (adjunct)
- Bipolar depression maintenance
What Sets This Drug Apart
- D3-preferring partial agonist (Ki 0.085 nM D3 vs 0.49 nM D2) — distinguishes it from aripiprazole; D3 preference may confer advantages for negative symptoms and motivation
- Active metabolite DDCAR has half-life of 1-3 weeks per FDA label; clinical effects may not reach steady state for 4-8 weeks and adverse effects can emerge weeks after dose changes
- Broadest monotherapy indication set among partial-agonist SGAs: schizophrenia, acute mania, and bipolar depression all FDA-approved as monotherapy
- Among the highest akathisia rates in the SGA class (20% vs 5% placebo in bipolar mania at 3-6 mg; RR 3.16 in schizophrenia)
- Mixed metabolic profile: LDL favorable (lowest P-score in NMA), triglycerides neutral, but glucose upper-quartile — monitor glucose more closely than lipids
- Prolactin-lowering signature shared with aripiprazole; low sexual dysfunction risk relative to risperidone/paliperidone
Boxed Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Increased Mortality in