CNS Drugs

, Volume 31, Issue 6, pp 513–525 | Cite as

Cariprazine: A Review in Schizophrenia

  • Karly P. Garnock-Jones
Adis Drug Evaluation


Cariprazine (Vraylar™) is a dopamine D3-preferring D2/D3 receptor partial agonist indicated for the treatment of patients with schizophrenia. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the use of cariprazine in patients with this disorder. In 6-week, phase IIb and III trials in patients with schizophrenia, cariprazine was significantly more efficacious than placebo in improving schizophrenia symptoms, including improvements in Positive and Negative Syndrome Scale (PANSS) total scores. It was associated with a significantly longer time to relapse than placebo in a long-term, phase III, relapse-prevention study. Cariprazine was also significantly more efficacious than risperidone in improving PANSS Factor Score for Negative Symptoms in a phase III trial in patients with predominantly negative symptoms of schizophrenia, a typically difficult to treat group of patients. Cariprazine was generally well tolerated in clinical trials, with most adverse events being of mild to moderate severity, and metabolic changes observed were considered generally not clinically significant. Cariprazine is a useful addition to the treatment options for schizophrenia, and may be of particular use in patients with predominantly negative symptoms.



During the peer review process, the manufacturer of cariprazine was also offered an opportunity to review this article. Any changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards


The preparation of this review was not supported by any external funding.

Conflict of interest

Karly Garnock-Jones is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information about this Adis Drug Review can be found at


  1. 1.
    National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management (CG178). 2014. Accessed 28 Apr 2017.
  2. 2.
    Heilbronner U, Samara M, Leucht S, et al. The longitudinal course of schizophrenia across the lifespan: clinical, cognitive, and neurobiological aspects. Harv Rev Psychiatry. 2016;24(2):118–28.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lehman AF, Lieberman JA, Dixon LB, et al. American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. 2nd ed. 2010. Accessed 28 Apr 2017.
  4. 4.
    Leucht S, Davis JM. Schizophrenia, primary negative symptoms, and soft outcomes in psychiatry. Lancet. 2017;389(10074):1077–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Nemeth G, Laszlovszky I, Czobor P, et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial. Lancet. 2017;389(10074):1103–13.CrossRefPubMedGoogle Scholar
  6. 6.
    Actavis Pharma Inc. Vraylar™ (cariprazine) capsules: US prescribing information. 2017. Accessed 28 Apr 2017.
  7. 7.
    Gross G, Wicke K, Drescher KU. Dopamine D(3) receptor antagonism - still a therapeutic option for the treatment of schizophrenia. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(2):155–66.CrossRefPubMedGoogle Scholar
  8. 8.
    Kiss B, Horvath A, Nemethy Z, et al. Cariprazine (RGH-188), a dopamine D3 receptor-preferring, D3/D2 dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther. 2010;333(1):328–40.CrossRefPubMedGoogle Scholar
  9. 9.
    Kiss B, Némethy Z, Laszlovszky I, et al. Pharmacological characteristics of major human metabolites of cariprazine [abstract no. P8-062]. In: 169th annual meeting of the American Psychiatric Association. 2016.Google Scholar
  10. 10.
    Girgis RR, Slifstein M, D’Souza D, et al. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO. Psychopharmacology (Berl). 2016;233(19–20):3503–12.CrossRefGoogle Scholar
  11. 11.
    Choi YK, Adham N, Kiss B, et al. Long-term effects of cariprazine exposure on dopamine receptor subtypes. CNS Spectr. 2014;19(3):268–77.CrossRefPubMedGoogle Scholar
  12. 12.
    Choi YK, Adham N, Kiss B, et al. Long-term effects of aripiprazole exposure on monoaminergic and glutamatergic receptor subtypes: comparison with cariprazine. CNS Spectr. 2017. doi: 10.1017/S1092852916000894.PubMedGoogle Scholar
  13. 13.
    Citrome L. Cariprazine in schizophrenia: clinical efficacy, tolerability, and place in therapy. Adv Ther. 2013;30(2):114–26.CrossRefPubMedGoogle Scholar
  14. 14.
    Zimnisky R, Chang G, Gyertyan I, et al. Cariprazine, a dopamine D3-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse. Psychopharmacology (Berl). 2013;226(1):91–100.CrossRefGoogle Scholar
  15. 15.
    Gyertyán I, Kiss B, Saghy K, et al. Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents. Neurochem Int. 2011;59(6):925–35.CrossRefPubMedGoogle Scholar
  16. 16.
    Watson DJ, King MV, Gyertyan I, et al. The dopamine D3-preferring D2/D3 dopamine receptor partial agonist, cariprazine, reverses behavioural changes in a rat neurodevelopmental model for schizophrenia. Eur Neuropsychopharmacol. 2016;26(2):208–24.CrossRefPubMedGoogle Scholar
  17. 17.
    Neill JC, Grayson B, Kiss B, et al. Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology. Eur Neuropsychopharmacol. 2016;26(1):3–14.CrossRefPubMedGoogle Scholar
  18. 18.
    Castner SA, Abbott AL, Adham N, et al. Subchronic treatment with the partial dopamine agonist cariprazine protects against ketamine-induced cognitive deficits in a nonhuman primate model relevant to schizophrenia [abstract no. M28]. Neuropsychopharmacology. 2014;39(Suppl):S129.Google Scholar
  19. 19.
    Periclou A, Phillips L, Bihorel S, et al. Characterization of population pharmacokinetics of cariprazine and its major metabolites [abstract no. 104]. In: 169th annual meeting of the American Psychiatric Association. 2016.Google Scholar
  20. 20.
    Nakamura T, Kubota T, Iwakaji A, et al. Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment). Drug Des Dev Ther. 2016;10:327–38.CrossRefGoogle Scholar
  21. 21.
    Carrothers T, Willavize S, Jaworowicz D, et al. Relationship of cariprazine plasma concentration to efficacy and safety in patients with schizophrenia or bipolar mania [abstract no. P6-014]. In: 169th annual meeting of the American Psychiatric Association. 2016.Google Scholar
  22. 22.
    Durgam S, Litman RE, Papadakis K, et al. Cariprazine in the treatment of schizophrenia: a proof-of-concept trial. Int Clin Psychopharmacol. 2016;31(2):61–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Durgam S, Starace A, Li D, et al. An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial. Schizophr Res. 2014;152(2–3):450–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Durgam S, Cutler AJ, Lu K, et al. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial. J Clin Psychiatry. 2015;76(12):e1574–82.CrossRefPubMedGoogle Scholar
  25. 25.
    Kane JM, Zukin S, Wang Y, et al. Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: results from an international, phase III clinical trial. J Clin Psychopharmacol. 2015;35(4):367–73.PubMedGoogle Scholar
  26. 26.
    Durgam S, Earley W, Li R, et al. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. Schizophr Res. 2016;176(2–3):264–71.CrossRefPubMedGoogle Scholar
  27. 27.
    Citrome L, Durgam S, Lu K, et al. The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials. J Clin Psychiatry. 2016;77(1):109–15.CrossRefPubMedGoogle Scholar
  28. 28.
    Fleischhacker W, Marder S, Lu K, et al. Efficacy of cariprazine vs. placebo across schizophrenia symptom domains: pooled analyses from 3 phase II/III trials [abstract no. T93]. Neuropsychopharmacology. 2014;39(Suppl):S351–2.Google Scholar
  29. 29.
    Durgam S, Laszlovszky I, Nagy K, et al. Categorical improvements in severity of mania and schizophrenia symptoms: pooled analyses of cariprazine phase II/III trials [abstract no. P-03-014]. Int J Neuropsychopharmacol. 2014;17(Suppl 1):54.Google Scholar
  30. 30.
    Debelle M, Faradzs-zade S, Szatmari B, et al. Cariprazine in negative symptoms of schizophrenia: post-hoc analyses of a fixed-dose phase III, randomized double-blind placebo-and active-controlled trial [abstract]. Eur Psychiatry. 2015;30(Suppl 1):242.CrossRefGoogle Scholar
  31. 31.
    Debelle M, Faradzs-zade S, Szatmari B, et al. Cariprazine in negative symptoms of schizophrenia: post hoc analyses of a fixed-dose, placebo-and active-controlled trial [abstract no. P.3.d.022]. Eur Neuropsychopharmacol. 2014;24(Suppl 2):S534.CrossRefGoogle Scholar
  32. 32.
    Earley W, Durgam S, Debelle M, et al. Cariprazine for negative symptoms of schizophrenia: pooled post hoc analysis of 2 randomized, double-blind, placebo-and active-controlled trials [abstract no. M204]. Neuropsychopharmacology. 2015;40(Suppl):S233–4.Google Scholar
  33. 33.
    Debelle M, Kahn R, Laszlovszky I, et al. Cariprazine as monotherapy for the treatment of predominant negative symptoms of patients with schizophrenia: a double-blind, active comparator-controlled trial [abstract no. M206]. Neuropsychopharmacology. 2015;40(Suppl):S235–6.Google Scholar
  34. 34.
    Durgam S, Greenberg WM, Li D, et al. Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study. Psychopharmacology (Berl). 2016;234(2):199–209.CrossRefGoogle Scholar
  35. 35.
    Cutler A, Durgam S, Wang Y, et al. Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study. CNS Spectr. 2017. doi: 10.1017/S1092852917000220.PubMedGoogle Scholar
  36. 36.
    Nasrallah HA, Cutler AJ, Wang Y, et al. Safety and tolerability of cariprazine in long-term treatment of schizophrenia: integrated summary of safety data [abstract no. P.3.d.025]. Eur Neuropsychopharmacol. 2014;24(Suppl 2):S536.CrossRefGoogle Scholar
  37. 37.
    Marder S, Zukin S, Lu K, et al. Metabolic safety of cariprazine in patients with schizophrenia [abstract no. M156]. Neuropsychopharmacology. 2015;40(Suppl):S205.Google Scholar
  38. 38.
    Remington G, Foussias G, Fervaha G, et al. Treating negative symptoms in schizophrenia: an update. Curr Treat Options Psychiatry. 2016;3:133–50.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kreyenbuhl J, Buchanan RW, Dickerson FB, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010;36(1):94–103.CrossRefPubMedGoogle Scholar
  40. 40.
    Haddad PM, Brain C, Scott J. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Relat Outcome Meas. 2014;5:43–62.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Higashi K, Medic G, Littlewood KJ, et al. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review. Ther Adv Psychopharmacol. 2013;3(4):200–18.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations