The review is devoted to comparative analysis of antipsychotics of three generations. When writing the review, a systematic search in the databases PubMed, Medline, Elsevier was carried out, a simple filter for keywords was used. Pharmacological and clinical issues of antipsychotic therapy were considered, the mechanisms of action of antipsychotics of different generations were revealed. Current trends in the development of approaches to the therapy of schizophrenia and the concept of “atypicality” of antipsychotics were discussed. A comparative analysis of indications for use, tolerance (safety of use) and efficacy of various antipsychotic drugs with an emphasis on the effect on negative (primary, persistent) symptoms has been conducted. The hypothesis underlying new approaches to the therapy of schizophrenia, based on the effect on dopamine autoreceptors, consisting of a high density of D2 and low density of D3 receptors, has been presented. It has been shown that antipsychotics of the third generation open up new possibilities in the therapy of psychosis within the framework of a personalized approach in psychiatry with the achievement of functional recovery of patients. The characteristics of the drugs – representatives of the third generation of antipsychotics – aripiprazole and cariprazine were given. The uniqueness of cariprazine as the only drug that inhibits D3 receptors in vitro, as well as in vivo in patients with schizophrenia was emphasized. The data of evidence-based studies of the effectiveness of cariprazine in the treatment of negative, including predominant negative symptoms were presented.

About the authors

Nataliia N. Petrova

Saint Petersburg State University, Saint Petersburg, Russia

Author for correspondence.
ORCID iD: 0000-0003-4096-6208

Russian Federation, 199034, Russia, St. Petersburg, Universitetskaya embankment, 7-9

Doctor of Medicine (MD), Professor, Head of the Department of Psychiatry and Narcology

Alexander G. Sofronov

I.I. Mechnikov North-West State Medical University), Saint Petersburg, Russia

ORCID iD: 0000-0001-6339-0198
SPIN-code: 4846-6528
Scopus Author ID: 18342314800

Russian Federation, 47 piskarevsky ave., Saint Petersburg, 195067, russia

Doctor of Medicine (MD), Professor, Corr. Member of RAS, Head of the Department of Psychiatry and Narcology


  1. Jones PB, Buckley PF. Schizophrenia. Philadelphia: Elsevier Health Sciences; 2006: 167.
  2. Gaebel W, Zielasek J. Schizophrenia in 2020: Trends in diagnosis and therapy. Psychiatry and Clinical Neurosciences. 2015; 69: 661-73. doi: 10.1111/pcn.12322.
  3. Buchanan RW. Persistent negative symptoms in schizophrenia: an overview. Schizophr Bull. 2007; 33: 1013-22. doi: 10.1093/schbul/sbl057.
  4. Arango C, Garibaldi G, Marder SR. Pharmacological approaches to treating negative symptoms: a review of clinical trials. Schizophr Res. 2013; 150: 346-52. doi: 10.1016/j.schres.2013.07.026.
  5. Möller HJ, Czobor P. Pharmacological treatment of negative symptoms in schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 2015; 265 (7): 567-78. doi: 10.1007/s00406-015-0596-y.
  6. Smith RC, Leucht S, Davis JM. Maximizing response to first-line antipsychotics in schizophrenia: a review focused on finding from meta-analysis. Psychopharmacology. 2019; 236: 545-59. doi: 10.1007/s00213-018-5133-z.
  7. Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: astate-of-the-art clinical review. Ther Clin Risk Manag. 2017; 13: 757-77. doi: 10.2147/TCRM.S11732.1
  8. Arango C, Buchanan RW, Kirkpatrick B, et al.. The deficit syndrome in schizophrenia: implications for the treatment of negative symptoms. Eur. Psychiatry. 2004; 19 (1): 21-6. doi: 10.1016/j.eurpsy.2003.10.004.
  9. Harvey RC, James AC, Shields GE. A Systematic Review and Network Meta-Analysis to Assess the Relative Efficacy of Antipsychotics for the Treatment of Positive and Negative Symptoms in Early-Onset Schizophrenia. CNS Drugs. 2016; 30: 27-39. doi: 10.1007/s40263-015-0308-1.
  10. Овсепян, А.А. Современные проблемы диагностики и терапии негативных и когнитивных симптомов и исходные состояния при шизофрении / А.А. Овсепян, П.В. Алфимов, Т.С. Сюняков // Психиатрия. – 2013. – Вып. 3. – № 59. – С. 71-76.
  11. Cerveri G, Gesi C, Mencacci C. Pharmacological treatment of negative symptoms in schizophrenia: update and proposal of a clinical algorithm. Neuropsychiatric Disease and Treatment. 2019; 15: 1525-35. doi: 10.2147/NDT.S201726.
  12. Leucht S, Corves C, Arbter D, et al. Second generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009; 373 (9657): 31-41. DOI: 10.1016/ S0140-6736(08)61764-X.
  13. Leucht S. Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2004; 7 (1): S15–S20. doi: 10.1017/S1461145704004109.
  14. Riedel M, Muller N, Strassnig M, et al. Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms. Eur Arch Psychiatry Clin Neurosci. 2005; 255(6): 432-37. doi: 10.1007/s00406-005-0622-6.
  15. Lindenmayer JP, Khan A, Iskander A, et al. A randomized controlled trial of olanzapine versus haloperidol in the treatment of primary negative symptoms and neurocognitive deficits in schizophrenia. J Clin Psychiatry. 2007; 68 (3): 368-79. doi: 10.4088/JCP.v68n0303.
  16. 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. Lancet. 2017; 389 (10074):1103-13. doi: 10.1016/S0140-6736(17)30060-0.
  17. Németh B, Molnár A, Akehurst R, et al. Quality-adjusted life year difference in patients with predominant negative symptoms of schizophrenia treated with cariprazine and risperidone. J Comp Eff Res. 2017; 6 (8): 639-48. doi: 10.2217/cer-2017-0024.
  18. Meltzer H, Nash F. Effects of antipsychotic drugs on serotonin receptors. Pharmacol Rev. 1991; 43 (4): 587-604.
  19. Kapur S, Seeman P. Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry. 2001; 158: 360-9. doi: 10.1176/appi.ajp.158.3.360.
  20. Мосолов, С.Н. Роль дофаминовых D3-рецепторов в механизме действия современных антипсихотиков / С.Н. Мосолов, П.В. Алфимов // Современная терапия психических расстройств. – 2014. – № 1. – С. 2-19.
  21. Kim DH, Stahl SM. Antipsychotic Drug Development. In: Swerdlow NR, editor. Behavioral Neurobiology of Schizophrenia and Its Treatment, Current Topics in Behavioral Neurosciences. Berlin: Springer_Verlag Berlin Heidelberg; 2010. doi: 10.1007/7854_2010_47.
  22. Шагиахметов, Ф.Ш. Атипичные антипсихотики: больше сходств или различий? Теоретические предпосылки / Ф.Ш. Шагиахметов // Современная терапия в психиатрии и неврологии. – 2014. – № 2. – С. 4-9.
  23. Ribeiro ELA, de Mendonça Lima T, Vieira MEB, et al. Efficacy and safety of aripiprazole for the treatment of schizophrenia: an overview of systematic reviews. Eur. J. Clin. Pharmacol. 2018; 74 (10): 1215-33. doi: 10.1007/s00228-018-2498-1.
  24. Richard B. Mailman and Vishakantha Murthy Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? Curr Pharm Des. 2010; 16 (5): 488-501. doi: 10.2174/138161210790361461.
  25. González-Maeso J, Weisstaub NV, Zhou M, et al. Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior. Neuron journal. 2007; 53(3): 439-52. doi: 10.1016/j.neuron.2007.01.008.
  26. Cussac D, Boutet-Robinet E, Ailhaud MC, et al. Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur. J. Pharmacol. 2008; 594 (1-3): 32-8. doi: 10.1016/j.ejphar.2008.07.040.
  27. Шмуклер, А.Б. Карипразин – антипсихотик с новыми уникальными потенциальными возможностями для лечения шизофрении и аффективных расстройств / А.Б. Шмуклер // Социальная и клиническая психиатрия. – 2014. – Т. 24. – № 2. – С. 72-75.
  28. Cariprazine Significantly Improved Negative Symptoms of Schizophrenia Based on Real Life Data from a New Observational Study by Gedeon Richter Plc. Prnewswire [Internet]. 2020. Available from:
  29. Davenport L. Cariprazine Trumps Risperidone for Negative Schizophrenia Symptoms. Medscape Medical News [Internet]. 2020. Available from:
  30. Laszlovszky I, Kiss B, Barabássy Á, et al. Cariprazine, a new type – dopamine D2 receptor preferring – partial agonist atypical antipsychotic for the treatment of schizophrenia and the primary negative symptoms. (Published in Hungarian with English abstract). Neuropsychopharmacol Hung. 2019; 21: 103-18.
  31. Earley W, Burgess M, Rekeda L, et al. Cariprazine Treatment of Bipolar Depression: A Randomized, Double Blind, Placebo-Controlled Phase 3 Study. Am J Psychiatry. 2019; 176: 439-48. doi: 10.1176/appi.ajp.2018.18070824.
  32. Szatmári B, Barabássy Á, Harsányi J, et al. Cariprazine safety in adolescents and the elderly: Analyses of clinical study data. Front Psychiatry. 2020; 11: 61. doi: 10.3389/fpsyt.2020.00061.
  33. Correll CU, Potkin SG, Zhong Y, et al. Long-term remission with cariprazine treatment in patients with schizophrenia: A post hoc analysis of a randomized, double-blind, placebo-controlled, relapse prevention trial. J Clin Psychiatry. 2019; 80 (2): 18m12495. doi: 10.4088/JCP.18m12495.
  34. Гурович, И.Я. Выздоровление при шизофрении. Концепция «recovery» / И.Я. Гурович, Е.Б. Любов, Я.А. Сторожакова // Социальная и клиническая психиатрия. – 2008. – Т. 18. – № 2. – С. 7-14.
  35. Kato T, Kanba S. Making psychiatry a clinical neuroscience-based medicine. Psychiatry and Clinical Neurosciences. 2019; 73 (1): 1. doi: 10.1111/pcn.12798.
  36. Perna G, Nemeroff CB. Personalized Medicine in Psychiatry: Back to the Future. Personalized medicine in psychiatry. 2017; 1-2: 1-84. doi: 10.1016/j.pmip.2017.01.001.
  37. Wium-Andersen IK, Vinberg M, Kessing MV, et al. Personalized medicine in psychiatry. Nordic Journal of Psychiatry. 2017; 71 (1): 1-8. doi: 10.1080/08039488.2016.1216163.

Supplementary files

There are no supplementary files to display.



Abstract - 45

PDF (Russian) - 5


Article Metrics

Metrics Loading ...




  • There are currently no refbacks.

Copyright (c) 2020 Pharmacy Formulas

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies