New treatment options for patients with mental disorders (literature review)
Abstract
This work provides an overview of the new drug cariprazine in particular, its pharmacodynamics (acts as a partial agonist of D2- and D3-dopamine receptors, agonist of 5-HT1A-serotonin receptors, antagonist of 5-HT2B-, 5-HT2A- and 5-HT2C-serotonin receptors), which fundamentally distinguishes the new drug from its predecessors; according to the pharmacokinetics, cariprazine has the longest half-life of 2 to 6 days among the oral antipsychotics on the market today; clinical trials, their results and side effects of the new drug, both independently and in comparison with other antipsychotic drugs, are considered.
About the Authors
E. M. Semyonova
South-Urals State Medical University
Russian Federation
Russian Federation
Chelyabinsk
E. V. Malinina
South-Urals State Medical University
Russian Federation
Russian Federation
Chelyabinsk
References
1. Быков Ю. В., Беккер Р. А., Морозов П. В. Эффективность карипразина в лечении шизофрении, особенно с преобладанием негативной симптоматики // Психиатрия и психофармакотерапия. 2018. № 5. С. 27–37.
2. Морозов П. В., Медведев В. Э. Карипразин — новый антипсихотик для лечения эндогенных психических расстройств // Психиатрия и психофармакотерапия. 2014. Т. 16, № 1. С. 9–14.
3. Шмуклер А. Б. Карипразин — антипсихотик с новыми уникальными потенциальными возможностями для лечения шизофрении и аффективных расстройств // Социальная и клиническая психиатрия. 2014. Т. 24, № 2. С. 72–75.
4. Caccia S., Invernizzi R. W., Nobili A. et al. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia // Therapeutics and Clinical Risk Management. 2013. Vol. 9. P. 319–328.
5. Calabrese J. R., Keck P. E. Jr., Starace A. et al. Efficacy and safety of low-and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study // The Journal of Clinical Psychiatry. 2014. Vol. 76, № 3. P. 284–292.
6. Calabrese J. R., Keck P. E. Jr., Starace A. et al. Efficacy and safety of low-and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study // The Journal of Clinical Psychiatry. 2014. Vol. 76, № 3. P. 284–292.
7. Choi Y. K., Adham N., Kiss B. et al. Long-term effects of cariprazine exposure on dopamine receptor subtypes // CNS Spectrums. 2014. Vol. 19, № 3. P. 268–277.
8. 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 // The Journal of Clinical Psychiatry. 2016. Vol. 77, № 1. P. 109–115.
9. Citrome L. Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability // Expert Opinion on Drug Metabolism & Toxicology. 2013. Vol. 9, № 2. P. 193–206.
10. Citrome L. Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy // Advances in Therapy. 2013. Vol. 30, № 2. С. 102–113.
11. Cutler A. J., 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 Spectrums. 2018. Vol. 23, № 1. P. 39–50.
12. De P. D. Cariprazine: New dopamine biased agonist for neuropsychiatric disorders // Drugs of Today (Barcelona, Spain: 1998). 2016. Vol. 52, № 2. P. 97–110.
13. Durgam S., Cutler A. J., Lu K. et al. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo-and active-controlled trial // The Journal of Clinical Psychiatry. 2015. Vol. 76, № 12. P. e1574–e1582.
14. 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 // Schizophrenia Research. 2016. Vol. 176, № 2–3. P. 264–271.
15. Durgam S., Greenberg W. M., 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. 2017. Vol. 234, № 2. P. 199–209.
16. 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 // Schizophrenia Research. 2014. Vol. 152, № 2–3. P. 450–457.
17. Earley W., Durgam S., Lu K. et al. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies // International Clinical Psychopharmacology. 2017. Vol. 32, № 6. P. 319–328.
18. Gyertyán I., Kiss B., Sághy 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 // Neurochemistry International. 2011. Vol. 59, № 6. P. 925–935.
19. Joyce J. N., Millan M. J. Dopamine D3 receptor antagonists as therapeutic agents // Drug Discovery Today. 2005. Vol. 10, № 13. P. 917–925.
20. Kane J. M., Zukin S., Wang Y. et al. Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: results from an international, phase III clinical trial // Journal of Clinical Psychopharmacology. 2015. Vol. 35, № 4. P. 367–373.
21. Kapás M., Pásztor Mészáros G., Yu B. et al. P.3.c.051 Comparison of the pharmacokinetic behaviour of RGH-188 in schizophrenic patients and healthy volunteers // European Neuropsychopharmacology. 2008. Vol. 18, suppl. 4. P. S433.
22. Keck P. E., Zukin S., Lu K. Efficacy of cariprazine on YMRS single items: a pooled analysis of 3 randomized double-blind, placebo-controlled trials in bipolar mania // Proceedings of the 29th CINP World College of Neuropsychopharmacology, Vancouver, British Columbia, Canada. 2014.
23. Kiss B., Horváth A., Némethy Z. et al. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile // Journal of Pharmacology and Experimental Therapeutics. 2010. Vol. 333, № 1. P. 328–340.
24. Kiss B., Laszlovszky I., Horváth A. et al. Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15 // Naunyn-Schmiedeberg's Archives of Pharmacology. 2008. Vol. 378, № 5. P. 515–528.
25. Laszlovsky I. et al. Dopamine D2/D3 receptor occupancy of RGH-188, a D3/D2 antagonist/partial agonist antipsychotic, in healthy volunteers // European Neuropsychopharmacology. 2007. Vol. 17 (Suppl. 4). P. 455.
26. Mészáros G. P. et al. Pharmacokinetics of RGH-188, a new dopamine D3/D2 antagonist/partial agonist atypical antipsychotic, in healthy subjects // European Neuropsychopharmacology. 2007. № 17. P. S451–S452.
27. Nasrallah H. A., Earley W., Cutler A. J. et al. The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis // BMC Psychiatry. 2017. Vol. 17, № 1. P. 305.
28. Németh 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 // The Lancet. 2017. Vol. 389, № 10074. P. 1103–1113.
29. Pásztor Mészáros G., Agai-Csongor E., Kapás M. Sensitive LC-MS/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine // Journal of Pharmaceutical and Biomedical Analysis. 2008. Vol. 48, № 2. P. 388–97.
30. Reynolds G. P. Histamine and antipsychotic drug-induced weight gain // Journal of Psychopharmacology. 2012. Vol. 26, № 12. P. 1608
31. Richelson E. New antipsychotic drugs: how do their receptor-binding profiles compare? // Journal of Clinical Psychiatry. 2010. Vol. 71, № 9. P. 1243–1244.
32. Roberts R. J., Findlay L. J., El-Mallakh P. L. et al. Update on schizophrenia and bipolar disorder: focus on cariprazine // Neuropsychiatric Disease and Treatment. 2016. Vol. 12. P. 1837–1842.
33. Seneca N., Finnema S. J., Laszlovszky I. et al. Occupancy of dopamine D₂ and D₃ and serotonin 5-HT₁A receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography // Psychopharmacology. 2011. Vol. 218, № 3. P. 579–587.
34. Stahl S. M. Case studies: Stahl's essential psychopharmacology. Cambridge University Press, 2011.
35. Stahl S. M. Case Studies: Stahl's Essential Psychopharmacology: Volume 2. Cambridge University Press. 1st ed. 2017.
36. Stahl S. M. Prescriber's Guide: Stahl's Essential Psychopharmacology. Cambridge University Press. 6th ed. 2016.
37. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press. 4th ed. 2013.
38. Werner F. M., Coveñas R. New developments in the management of schizophrenia and bipolar disorder: potential use of cariprazine // Therapeutics and Clinical Risk Management. 2015. Vol. 11. P. 1657.
39. Zimnisky R.б Chang G., Gyertyán I. et al. Cariprazine, a dopamine D(3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse // Psychopharmacology. 2013. Vol. 226, № 1. P. 91–100.
40. Fleischhacker W., Galderisi S., Laszlovszky I. et al. The efficacy of cariprazine in negative symptoms of schizophrenia: Post hoc analyses of PANSS individual items and PANSS-derived factors // European Psychiatry. 2019. Vol. 58. P. 1–9.
41. Sachs G. Results from three pivotal trials support Vraylar for bipolar I depression [Internet] // Psychiatric Annals. Vol. 45. URL: https://www.healio.com/psychiatry/bipolar-disorder/news/online/%7B6c9e12a4-e17f-4846-b046-6a5731309eee%7D/results-from-three-pivotal-trials-support-vraylar-for-bipolar-i-depression (дата обращения: 11.02.2020).
42. Allergan, Richter Report Positive Topline Results From Third Cariprazine Trial [Internet]. URL: https://markets.businessinsider.com/news/stocks/allergan-richter-report-positive-topline-results-from-third-cariprazine-trial-1020342427 (дата обращения: 11.02.2020).
Review
For citations:
Semyonova E.M., Malinina E.V. New treatment options for patients with mental disorders (literature review). Title in english. 2020;15(2):31-39. (In Russ.)
Views:
96
Email this article 