Cariprazine for the Treatment of Bipolar Disorder

Perspectives in Psychiatric Care

Volumn 53, Issue 3, 2017, Pages 148-155

  Findlay, Lillian Jan ^a   El Mallakh, Peggy L ^a   El Mallakh, Rif S ^b  

^a UNIVERSITY OF KENTUCKY   (United States)

^b University of Louisville School of Medicine   (United States)

Author keywords

Bipolar depression; bipolar disorder; cariprazine; dopamine D2 receptor; dopamine D3 receptor; mania

Indexed keywords

CARIPRAZINE; DOPAMINE RECEPTOR STIMULATING AGENT; NEUROLEPTIC AGENT; PIPERAZINE DERIVATIVE;

BIPOLAR DISORDER; HUMAN;

ANTIPSYCHOTIC AGENTS; BIPOLAR DISORDER; DOPAMINE AGONISTS; HUMANS; PIPERAZINES;

EID: 84962833207     PISSN: 00315990     EISSN: 17446163     Source Type: Journal    
DOI: 10.1111/ppc.12150     Document Type: Review

References (57)

1. 2 receptors. Bioorganic and Medicinal Chemistry Letters, 22, 3437–3440.
2. Anonymous. (2014). Cariprazine performs well for schizophrenia, bipolar mania. Current Psychiatry. Retrieved from http://www.currentpsychiatry.com/home/article/cariprazine-performs-well-for-schizophrenia-bipolar-mania/d003a3cfa939d896e7ae82c56b012a92.html
3. Bakker, P. R., van Harten, P. N., & van Os, J. (2006). Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: A meta analysis. Schizophrenia Research, 83(2-3), 185–192.
4. Barth, V., Need, A. B., Tzavara, E. T., Giros, B., Overshiner, C., Gleason, S. D.,.. Witkin, J. M. (2013). In vivo occupancy of dopamine D3 receptors by antagonists produces neurochemical and behavioral effects of potential relevance to attention-deficit-hyperactivity disorder. Journal of Pharmacology and Experimental Therapeutics, 344(2), 501–510.
5. 2 receptor mRNA. Brain Research, 564, 203–219.
6. Burris, K. D., Molski, T. F., Xu, C., Ryan, E., Tottori, K., Kikuchi, T., … Molinoff, P. B. (2002). Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. Journal of Pharmacology and Experimental Therapeutics, 302(1), 381–389
7. Caccia, S., Invernizzi, R. W., Nobili, A., & Pasina, L. (2013). A new generation of antipsychotics: Pharmacology and clinical utility of cariprazine in schizophrenia. Therapeutic Clinical Risk Management, 9, 319–328.
8. Citrome, L. (2013a). Cariprazine in schizophrenia: Clinical efficacy, tolerability, and place in therapy. Advances in Therapy, 30(2), 114–126.
9. Citrome, L. (2013b). Cariprazine: Chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opinion in Drug Metabolism and Toxicology, 9(2), 193–206.
10. Citrome, L. (2013c). A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: An evidenced-based medicine approach. CNS Drugs, 27, 879–911.
11. ClinicalTrials.gov. (2015). Cariprazine relative to placebo in the prevention of relapse of symptoms in patients with schizophrenia. Retrieved from https://clinicaltrials.gov/ct2/show/NCT01412060
12. Cosi, C., Carilla-Durand, E., Assié, M. B., Ormiere, A. M., Maraval, M., Leduc, N., & Newman-Tancredi, A. (2006). Partial agonist properties of the antipsychotics SSR181507, aripiprazole and bifeprunox at dopamine D2 receptors: G protein activation and prolactin release. European Journal of Pharmacology, 535(1–3), 135–144.
13. Cutler, A., Lieberman, J., Wan, S., Migliore, R., Laszlovszky, I., Németh, G., & Durgam, S. (2015). Cariprazine in acute exacerbation of schizophrenia: A fixed-dose phase iii, randomized, double-blind, placebo- and active-controlled trial. Presented at the PsychCongress, Chicago, IL. Retrieved from http://www.psychcongress.com/posters/cariprazine-acute-exacerbation-schizophrenia-fixed-dose-phase-iii-randomized-double-blind.
14. 3 receptors on neurotensin mRNA expression in nucleus accumbens. European Journal of Neuroscience, 6, 1384–1387.
15. Durgam, S., Nasrallah, H. A., Cutler, A., Wang, Y., Lu, K., Nagy, K., & Laszlovszky, I. (2014). Safety and tolerability of cariprazine in long-term treatment of schizophrenia: Integrated summary of safety data (poster #P-05-027). Presented at the International College of Neuropsychopharmacology (CINP) 29th World Congress, June 22–26, 2014, Vancouver, Canada, and announced in a press release. Retrieved from http://www.prnewswire.com/news-releases/richter-and-actavis-announce-positive-phase-iii-results-for-cariprazine-in-the-prevention-of-relapse-in-patients-with-schizophrenia-300022547.html
16. Durgam, S., Starace, A., Li, D., Migliore, R., Ruth, A., Nemeth, G., & Laszlovsky, I. (2014). An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: A phase II, randomized clinical trial. Schizophrenia Research, 152, 450–457.
17. Durgam, S., Starace, A., Li, D., Migliore, R., Ruth, A., Nemeth, G., & Laszlovsky, I. (2015). The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: A phase II trial. Bipolar Disorders, 17(1), 63–75.
18. El-Mallakh, R. S., Elmaadawi, A. Z., Gao, Y., Lohano, K., & Roberts, R. J. (2011). Current and emerging therapies for the management of bipolar disorders. Journal of Central Nervous System Disorders, 3, 189–197.
19. Forest Laboratories, Inc. (2010). Forest Laboratories, Inc. and Gedeon Richter Plc announce results from a phase II study of cariprazine for the treatment of bipolar depression. Press release, August 30, 2010. Retrieved from http://news.frx.com/press-release/rd-news/forest-laboratories-inc-and-gedeon-richter-plc-announce-results-phase-ii-stu-0
20. Forest Laboratories, Inc. (2011). Forest Laboratories, Inc. and Gedeon Richter Plc announce results from a phase II study of cariprazine as adjunctive therapy in major depressive disorder. Press release, February 28, 2011. Retrieved from http://investor.frx.com/press-release/rd-news/forest-laboratories-inc-and-gedeon-richter-plc-announce-results-phase-ii-study.
21. Forest Laboratories, Inc. (2012a). Forest Laboratories, Inc. and Gedeon Richter Plc. announce results from two positive phase III trials with the investigational antipsychotic cariprazine for the treatment of schizophrenia. Press release, February 28, 2012. Retrieved from http://news.frx.com/press-release/rd-news/forest-laboratories-inc-and-gedeon-richter-plc-announce-results-two-positive-p.
22. Forest Laboratories, Inc. (2012b). Forest Laboratories, Inc. and Gedeon Richter Plc. announce of results from two phase III trials with the investigational antipsychotic cariprazine for the treatment of schizophrenia. Press release, November 6, 2012. Retrieved from http://news.frx.com/press-release/rd-news/forest-laboratories-inc-and-gedeon-richter-plc-announce-results-two-positive-p.
23. Forest Laboratories, Inc. (2014a). Forest Laboratories, Inc. and Gedeon Richter Plc. announce positive phase IIb topline results for cariprazine for the treatment of bipolar depression. Press release, March 31, 2014. Retrieved from http://investor.frx.com/press-release/r-and-d-news/forest-laboratories-inc-and-gedeon-richter-plc-announce-positive-phase–0.
24. Forest Laboratories, Inc. (2014b). Forest Laboratories, Inc. and Gedeon Richter Plc. announce positive phase IIb topline results for cariprazine as adjunctive therapy in the treatment of major depressive disorder. Press release, March 21, 2014. Retrieved from http://investor.frx.com/press-release/r-and-d-news/forest-laboratories-inc-and-gedeon-richter-plc-announce-positive-phase-ii.
25. Fountoulakis, K. N., Kelsoe, J. R., & Akiskal, H. (2012). Receptor targets for antidepressant therapy in bipolar disorder: An overview. Journal of Affective Disorders, 138(3), 222–238.
26. 2 receptor ß-arrestin interactions. Pharmacology Research Perspectives, 3(1), e00073.
27. George, M., Amrutheshwar, R., Rajkumar, R. P., Kattimani, S., & Dkhar, S. A. (2013). Newer antipsychotics and upcoming molecules for schizophrenia. European Journal of Clinical Pharmacology, 69, 1497–1509.
28. Gross, G., Wicke, K., & Drescher, K. U. (2013). Dopamine D₃ receptor antagonism – Still a therapeutic option for the treatment of schizophrenia. Naunyn Schmiedeberg's Archives of Pharmacology, 386(2), 155–166.
29. Gründer, G., Kungel, M., Ebrecht, M., Göröcs, T., & Modell, S. (2006). Aripiprazole: Pharmacodynamics of a dopamine partial agonist for the treatment of schizophrenia. Pharmacopsychiatry, 39(Suppl. 1), S21–S25.
30. Gyertyán, I., Kiss, B., Sághy, K., Laszy, J., Szabó, G., Szabados, T.,.. Szombathelyi, Z. (2011). 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. Neurochemistry International, 59(6), 925–935.
31. Horacek, J., Bubenikova-Valesova, V., Kopecek, M., Palenicek, T., Dockery, C., Mohr, P., & Höschl, C. (2006). Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs, 20(5), 389–409.
32. Javitt, D. C. (2015). Current and emergent treatments for symptoms and neurocognitive impairment in schizophrenia. Current Treatment Options in Psychiatry, 1, 107–120.
33. Johnson, M., Kozielska, M., Pilla Reddy, V., Vermeulen, A., Barton, H.A., Grimwood, S.,.. Proost, J. H. (2014). Dopamine D2 receptor occupancy as a predictor of catalepsy in rats: A pharmacokinetic-pharmacodynamic modeling approach. Pharmacy Research, 31(10), 2605–2617.
34. Kapás, M., Pásztor Mészáros, G., Yu, B., Shi, J., Knoche, B., Laszlovszky, I., & Bolton, G. (2008). (P.3.c.051) Comparison of the pharmacokinetic behaviour of RGH-188 in schizophrenic patients and healthy volunteers. European Neuropsychopharmacology, 18(Suppl. 4), S433.
35. Kapur, S., Remington, G., Jones, C., Wilson, A., DaSilva, J., Houle, S., & Zipursky, R. (1996). High levels of dopamine D-2 receptor occupancy with low-dose haloperidol treatment: A PET study. American Journal of Psychiatry, 153(7), 948–950.
36. Kapur, S., Zipursky, R., Roy, P., Jones, C., Remington, G., Reed, K., & Houle, S. (1997). The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: A PET study. Psychopharmacology (Berlin), 131(2), 148–152.
37. Kirschner, N., Gémesi, L. I., Vastag, M., Ágaine-Csongor, É., Domány, G., Kapás, M., & Tihany, K. (2008). In vitro metabolism of RGH-188. Presented at the 10th European International Society of the Study of Xenobiotics (ISSX), Meeting, May 18–21, Vienna, Austria. Retrieved from https://issx.confex.com/issx/10euro/webprogram/Paper8686.html
38. 2 dopamine receptor antagonist-partial agonist antipsychotic candidate: In vitro and neurochemical profile. Journal of Pharmacology and Experimental Therapeutics, 333(1), 328–340.
39. Laszlovsky, I., Németh, G., Mészáros, P., Kapás, M., Brooks, D. J., Pavese, N., & Szombathelyi, Z. (2007). (P.3.c.053) Dopamine D2/D3 receptor occupancy of RGH-188, a D3/D2 antagonist/partial agonist antipsychotic, in healthy volunteers. European Neuropsychopharmacology, 17(Suppl. 4), S455.
40. Leucht, S., Samara, M., Heres, S., Patel, M. X., Woods, S. W., & Davis, J. M. (2014). Dose equivalents for second-generation antipsychotics: The minimum effective dose method. Schizophrenia Bulletin, 40(2), 314–326.
41. Lieberman, J., Cutler, A., Wan, S., Migilore, R., Ruth, A., Laslovsky, I., … Durgam, S. (2013). Cariprazine in acute exacerbation of schizophrenia: A fixed-dose randomised, double-blind, placebo-and-active-controlled trial. European Neuropsychopharmacology, 23, S477–S478.
42. Litman, R., Papadakis, K., Durgam, S., & Xie, J. (2008). Use of cariprazine in the treatment of schizophrenia: A proof-of-concept trial. Poster Presentation 61, 60th Institute on Psychiatric Services of the American Psychiatric Association, October 2–5, Chicago, IL.
43. Madras, B. K. (2013). History of the discovery of the antipsychotic dopamine D2 receptor: A basis for the dopamine hypothesis of schizophrenia. Journal of the History of Neuroscience, 22(1), 62–78.
44. Nordstrom, A. L., Farde, L., Wiesel, F. A., Forslund, K., Pauli, S., Halldin, C., & Uppfeldt, G. (1993). Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects – A double-blind PET study of schizophrenic-patients. Biological Psychiatry, 33(4), 227–235.
45. Papp, M., Gruca, P., Lasoń-Tyburkiewicz, M., Adham, N., Kiss, B., & Gyertyán, I. (2014). Attenuation of anhedonia by cariprazine in the chronic mild stress model of depression. Behavioural Pharmacology, 25(5-6), 567–574.
46. Pásztor Mészáros, G., Agai-Csongor, E., & Kapaś, M. (2008). Sensitive LC-MS/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-cariprazine in human plasma and urine. Journal of Pharmaceutical and Biomedical Analysis, 48(2), 388–397.
47. Pásztor Mészáros, G., Kapás, M., Borsos, M., Laszlovszky, I., Németh, G., Tihanyi, K., & Szombathelyi, Z. (2007). (P.3.c.047) Pharmacokinetics of RGH-188, a new dopamine D3/D2 antagonist/partial agonist atypical antipsychotic, in healthy subjects. European Neuropsychopharmacology, 17(Suppl. 4), S451–S452.
48. Potkin, S., Keator, D., Mukherjee, J., Preda, A., Highum, D., Gage, A.,.. Laszlovsky, I. (2009). (P.1.e.028) Dopamine D3 and D2 receptor occupancy of cariprazine in schizophrenic patients. European Neuropsychopharmacology, 19(Suppl. 3), S316.
49. 3 receptors in islands of Calleja and shell of nucleus accumbens of the rat: Opposite and synergistic functional interactions. European Journal of Neuroscience, 10, 1676–1686.
50. Seeman, P. (2002). Atypical antipsychotics: Mechanism of action. Canadian Journal of Psychiatry, 47, 27–38.
51. Sheynikhovich, D., Otani, S., & Arleo, A. (2011). The role of tonic and phasic dopamine for long-term synaptic plasticity in the prefrontal cortex: A computational model. Journal of Physiology Paris, 105(1–3), 45–52.
52. Sokoloff, P., Diaz, J., Levesque, D., Pilon, C., Dimitriadou, V., Griffon, N.,.. Schwartz, J. C. (1995). Novel dopamine receptor subtypes as targets for antipsychotic drugs. Annals of the New York Academy of Sciences, 757, 278–292.
53. 3) as a target for neuroleptics. Nature, 347, 146–151.
54. Thase, M. E., Jonas, A., Khan, A., Bowden, C. L., Wu, X., McQuade, R. D.,.. Owen, R. (2008). Aripiprazole monotherapy in nonpsychotic bipolar I depression: Results of 2 randomized, placebo-controlled studies. Journal of Clinical Psychopharmacology, 28(1), 13–20.
55. 11C]raclopride. Neuropsychopharmacology, 27(2), 248–259.
56. 3-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse. Psychopharmacology (Berlin), 226(1), 91–100.
57. Zukin, S. R., Kane, J., Cutler, A. J., Wang, Y., Mokliatchouk, O., Laslovsky, I., & Durgam, S. (2012). Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: A phase III, international, randomized, double-blind, placebo-controlled trial. Neuropsychopharmacology, 38(S1), S319.