Cariprazine and Aripiprazole in inpatient schizophrenia therapy. Comparative analysis of the parameters of the effectiveness and safety of antipsychotics

Background: the drugs cariprazine and aripiprazole, from the group of third-generation antipsychotics, are recommended for both inpatient and outpatient treatment of schizophrenia, primarily to correct negative symptoms and minimize the risk of endocrine side effects caused by previous generations of drugs. The relevance of this study is due to the lack of research, including data from domestic psychiatric practice. The objectives of this research are to conduct a direct comparison of the effcacy and safety profiles of cariprazine and aripiprazole for the treatment of schizophrenia. Eliminating this information gap will undoubtedly contribute to optimizing the therapeutic process by personalizing the choice of antipsychotic medication. The aim of this study is to compare the therapeutic efficacy and safety of cariprazine versus aripiprazole during inpatient treatment for schizophrenia. Patients and Methods: an eight-week observational study was conducted at the V.M. Bekhterev National Research Medical Center for Psychiatry and Neurology. Thirty-eight inpatient patients participated in the study, including 20 men and 18 women, aged 18 to 68 years, with a diagnosis of paranoid schizophrenia (F20.0) who had a positive response to therapy (at least a 30% reduction in total score on the Positive and Negative Syndrome Scale [PANSS]). Two groups of patients were formed based on monotherapy with atypical antipsychotics of the third generation: group I received cariprazine, and group II received Aripiprazole. Clinical and psychopathological assessments, psychometric measurements (PANSS and UKU scales), anthropometric measurements, and laboratory tests were conducted. Statistical analysis was also performed. Results: the analysis of psychometric indicators in dynamics showed that in both groups, there was a significant reduction in symptoms, as measured by the total PANSS score, by 14.0 (95% CI (2.2–25.8), p = 0.026) and 12.0 (95% CI (3.4–20.6), p = 0.013), in the first and second groups respectively. At the same time, among patients taking cariprazine, the decrease in negative symptoms on the PANSS subscale was statistically significant, amounting to – 4.3 points (95% CI (–9.3 — –0.3), p = 0.039). During 8 weeks of aripiprazole therapy, no significant changes in metabolic parameters were observed. In contrast, in the group of patients receiving cariprazine, a reduction in body weight of 1.8 kg (95% CI (1.3–2.3), p < 0.001) and a decrease in total fat percentage of –2.3% (95% CI (–3.3 — 1.3), p < 0.001) were observed. Conclusions: the results of this study suggest that cariprazine monotherapy may be more effective than aripiprazole for treating negative symptoms. Both, cariprazine and aripiprazole, have shown good tolerability and a low risk of side effects.

1. Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, Kissling W, Davis JM, Leucht S. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010;123(2-3):225-233. doi: 10.1016/j.schres.2010.07.012

2. Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review. J Clin Psychiatry. 2009;70:1041-1050. doi: 10.4088/jcp.08r04392

3. Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, Arndt T, Bäckers L, Rothe P, Cipriani A, Davis J, Salanti G, Leucht S. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019 Sep 14;394(10202):939-951. doi: 10.1016/S0140-6736(19)31135-3. Epub 2019 Jul 11. Erratum in: Lancet. 2019 Sep 14;394(10202):918. doi: 10.1016/S0140-6736(19)31677-0. PMID: 31303314; PMCID: PMC6891890.

4. Pillinger T, McCutcheon RA, Vano L. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(1):64-77. doi: 10.1016/S2215-366(19)30416-X

5. Caccia S, Invernizzi RW, Nobili A, Pasina L. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia. Ther Clin Risk Manag. 2013;9:319-328. doi: 10.2147/TCRM.S35137

6. Gyertyán I, Kiss B, Sághy K, Laszy J, Szabó G, Szabados T, Gémesi LI, Pásztor G, Zájer-Balázs M, Kapás M, Csongor EÁ, Domány G, Tihanyi K, Szombathelyi Z. 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 Nov;59(6):925-935. doi: 10.1016/j.neuint.2011.07.002. Epub 2011 Jul 13. PMID: 21767587.

7. Solmi M, Murru A, Pacchiarotti I, Undurraga J, Veronese N, Fornaro M, Stubbs B, Monaco F, Vieta E, Seeman MV, Correll CU, Carvalho AF. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017 Jun 29;13:757-777. doi: 10.2147/TCRM.S117321. PMID: 28721057; PMCID: PMC5499790.

8. Sapra M., Lawson D., Iranmanesh A. Fat Distribution in Schizophrenia Patients: A Pilot Study Comparing First-and Second-Generation Antipsychotics. J Clin Psychopharmacol. 2018;38:68-71. doi: 10.1097/JCP.0000000000000810

9. Sowel M, Mukhopadhyay N, Cavazzoni P, Carlson C, Mudaliar S, Chinnapongse S. Evalua-tion of insulin sensitivity in healthy volunteers treated with olanzapine, risperidone, orplacebo: A prospective, randomized study using the two-step hyperinsulinemic, euglycemicclamp. J Clin Endocrinol Metab. 2003;88:5875-5880. doi: 10.1210/jc.2002-021884

10. Koro CE, Fedder DO, L’Italien GJ, Weiss SS, Magder LS, Kreyenbuhl J, Revicki DA, Buchanan RW. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002 Aug 3;325(7358):243. doi: 10.1136/bmj.325.7358.243. PMID: 12153919; PMCID: PMC117636.

11. Thakore JH, Mann JN, Vlahos I, Martin A, Reznek R. Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia. Int J Obes Relat Metab Disord. 2002;26:137-141. doi: 10.1038/sj.ijo.0801840

12. Kim SF, Huang AS, Snowman AM, Teuscher C, Snyder SH. From the cover: antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proc Natl Acad Sci U S A. 2007;104(9):3456-3459. doi: 10.1073/pnas.0611417104

13. Petrova NN, Sofronov AG. Antipsychotics: from first to third generation. Pharmacy Formulas. 2020;2(4):82- 89. (In Russ.). doi: 10.17816/phf55260

14. Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple-treatments meta-analysis. Lancet. 2013;382:951-962. doi: 10.1016/S0140-6736(13)60733-3

15. Heidbreder CA, Newman AH. Current perspectives on selective dopamine D(3) receptor antagonists as pharmacotherapeutics for addictions and related disorders. Ann N Y Acad Sci. 2010;1187:4-34. doi: 10.1111/j.1749-6632.2009.05149.x

16. Corponi F, Fabbri C, Bitter I, Montgomery S, Vieta E, Kasper S, Pallanti S, Serretti A. Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone. Eur. Neuropsychopharmacol.2019;29:971-985. doi: 10.1016/j.euroneuro.2019.06.008

17. Durgam S, Greenberg WM, Li D, Lu K, Laszlovszky I, Nemeth G, Migliore R, Volk S. 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). 2017;234(2):199-209. doi: 10.1007/s00213-016-4450-3

18. Pillinger T, McCutcheon RA, Vano L. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(1):64-77. doi: 10.1016/S2215-366(19)30416-X

19. Oleychik IV, Baranov PA, Shishkovskaya TI. The use of the atypical third-generation antipsychotic aripiprazole (Zilaxera®) in the treatment of depressive conditions developed within the framework of schizophrenia: a study of efficacy and safety. Psychiatry (Moscow) (Psikhiatriya). 2023;21(3):6-19. (In Russ.). doi: 10.30629/2618-6667-2023-21-3-6-19

20. Kerwin R, Millet B, Herman E. A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study. Eur Psychiatry. 2007;22(7):433-443. doi: 10.1016/j.eurpsy.2007.03.002

21. Veerman SRT, Schulte PFJ, de Haan L. Treatment for Negative Symptoms in Schizophrenia: A Comprehensive Review. Drugs. Springer International Publishing. 2017;77:1423-1459. doi: 10.1007/s40265-017-0789-y

22. Bak M, Drukker M, Cortenraad S, Vandenberk E, Guloksuz S. Antipsychotics result in more weight gain in antipsychotic naive patients than in patients after antipsychotic switch and weight gain is irrespective of psychiatric diagnosis: A meta-analysis. PLoS One. 2021 Feb 17;16(2):e0244944. doi: 10.1371/journal.pone.0244944. PMID: 33596211; PMCID: PMC7888647.

23. Newcomer JW, Campos JA, Marcus RN, Breder C, Berman RM, Kerselaers W, L’italien GJ, Nys M, Carson WH, McQuade RD. A multicenter, randomized, double-blind study of the effects of aripiprazole in overweight subjects with schizophrenia or schizoaffective disorder switched from olanzapine. J Clin Psychiatry. 2008 Jul;69(7):1046-1056. doi: 10.4088/jcp.v69n0702. PMID: 18605811.

24. Mazo GE, Yakovleva YaV. Methods of correction of hyperprolactinemia induced by antipsychotics: current state of the problem and development prospects. V.M. Bekhterev review of psychiatry and medical рsychology. 2024;58(2):107-115. (In Russ.). doi: 10.31363/2313-7053-2024-2-972

25. Vasiliu O. Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence? Front Psychiatry. 2022;13:1069432. doi: 10.3389/fpsyt.2022.1069432.