Cariprazine (CAR) is an antipsychotic drug for the treatment of schizophrenia (SCZ) and bipolar disorder (BD), and it acts as a partial agonist on the dopamine receptors (DR), D2, and D3. Although many single nucleotide polymorphisms (SNPs) in genes coding for these receptors are known to influence response to antipsychotics, to date, no study on CAR pharmacogenetics exists. In this pilot study, we investigated the relationship between SNPs in DRD2 (rs1800497 and rs6277) and DRD3 (rs6280), and response to CAR treatment, evaluated by the psychometric Brief Psychiatric Rating Scale (BPRS), in a cohort of Caucasian patients. We found a significant association between DRD2 rs1800497 and rs6277 and response to CAR treatment. When genotypes were combined into an arbitrary score, the receiver operating characteristic curve analysis showed that using a cut-off value of −2.5 the response to CAR treatment could be predicted with a positive likelihood ratio of 8.0. Our study report, for the first time, a correlation between SNPs in DRD2 and response to CAR treatment. After confirmation in a larger cohort of patients, our results could open the way for the identification of new tools for the provision of response to CAR treatment.

IntroductionCariprazine is a third-generation antipsychotic, approved for the treatment of schizophrenia and bipolar disorder and used off-label for schizoaffective disorder and treatment-resistant depression. Cariprazine is a partial agonist at dopamine receptors D2 and D3 and serotonin receptor 5HT1A and an antagonist at serotonin receptors 5HT2B and 5HT2A. It is metabolized by CYP3A4 in desmetyl-cariprazine and didesmethyl-cariprazine, both active metabolites with a half-life of 1–2 days and 2–3 weeks, respectively.Case ReportHere we show the cases of 3 outpatients diagnosed with bipolar I disorder (two patients) and schizoaffective disorder (one patients) and characterized by low adherence to treatment, satisfactory cognitive and personal functioning and average disease severity to whom we administered cariprazine as a monotherapy, on a two-times a week schedule (i.e., every 72–96 h). We evaluated response to treatment and disease remission according to conventional definitions, using rating scales BPRS, PANSS and BDI-II. Two-times a week treatment was set either after a disease relapse (one patient), after a sustained remission obtained with daily administration of cariprazine (one patient) or since our first evaluation (one patient). After 4 weeks of treatment all three patients satisfied criteria for response to treatment and remission, a result that was sustained for 8 (in one patients) and 12 months (in other two patients) and still ongoing.DiscussionReported results support our hypothesis that long half-lives of cariprazine and its metabolites provide an adequate therapeutic response with a two-times a week administration. In selected patients, cariprazine administered as a “oral long-acting” seems effective in treating acute episodes of illness and in sustaining remission, combining advantages of oral and long-acting injectable antipsychotics concerning therapeutic alliance.