Dugodelujući antipsihotici druge generacije: izazovi i prednosti tretmana dostupnih preparata

Ana Munjiza Jovanović; Danica Milenković; Čedo Miljević

doi:10.5937/engrami47-57138

Ana Munjiza Jovanović Institut za mentalno zdravlje, Beograd, Srbija
Danica Milenković Institut za mentalno zdravlje, Beograd, Srbija
Čedo Miljević Univerzitet u Beogradu, Medicinski fakultet, Beograd ; Srbija Institut za mentalno zdravlje, Beograd, Srbija https://orcid.org/0000-0002-8306-133X

DOI: https://doi.org/10.5937/engrami47-57138

Ključne reči: dugodelujući antipsihotici, risperidone mikrosvere,, risperidone ISM, paliperidon-palmitat

Sažetak

Dugodelujući antipsihotici su razvijeni u drugoj polovini dvadesetog veka kao važni element u procesu deinstitualizacije psihijatrijskih pacijenata. Danas je njihova uloga značajna i u poboljšanju komplijanse, postizanju stabilne koncetracije leka u plazmi ali i prevencije relapse i unapređenju kognitivnog funkcionisanja kod hroničnih pacijenata. Iako je unazad dve decenije registrovana nekolicina dugodelujućih preparata druge i treće generacije antipsihotika, u našoj sredini su trenutno registrovana samo četiri preparata: dugodelujući risperidone mikrosvere i baziran na in situ mikropartikulama (ISM); paliperidone palmitat formulacije na jedan i tri meseca. Ovaj pregledni rad ima za cilj da prikaže njihovu farmakokinetiku i farmakodinamiku, kliničku efikasnost, neželjene efekte i izazove pri titraciji i međusobnoj zameni ovih preparata.

Ključne reči: dugodelujući antipsihotici; risperidone mikrosvere, risperidone ISM, paliperidone-palmitat

Biografija autora

Danica Milenković, Institut za mentalno zdravlje, Beograd, Srbija

doktor medicine, aktuelno volonter

Reference

Crocq MA. Histoire des traitements antipsychotiques à action prolongée dans la schizophrénie [A history of antipsychotic long-acting injections in the treatment of schizophrenia]. Encephale. 2015; 41(1):84-92. French. Doi: 10.1016/j.encep.2014.12.002.

Wing, JK, Brown, GW. Social treatment of chronic schizophrenia: a comparative study of three mental hospitals. J Ment Sci 1961; 107:847–61.

Ley P, Spelman MS. Communicating with the Patient. Staples Press.1667; 37–78.

Hogarty GE, Schooler NR, Ulrich R, Mussare F, Ferro P, Herron E. Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride. Arch Gen Psychiatry. 1979; 36:1283–94. Doi:10.1001/archpsyc.1979.01780120013001.

Hogarty GE, Ulrich R, Goldberg SC. Sociotherapy and the prevention of relapse among schizophrenic patients. In Evaluation of Psychological Therapies (eds Spitzer, RL, Klein, DF): Johns Hopkins University Press; 1976; 285–93. PMID: 177968.

Pietzcker A, Gaebel W, Kopcke W, Linden M, Muller P. A German multicenter study on the neuroleptic long-term therapy of schizophrenic patients. Pharmacopsychiatry 1986; 19:161–6 Doi: 10.1016/0022-3956(93)90059-B.

Kissling W (ed). Neuroleptic relapse prevention. In Guidelines for Neuroleptic Relapse Prevention in Schizophrenia Springer; 1991; 50–2. Doi: 10.1007/978-3-642-86922-8_12.

Maric NP, Jovicic MJ, Mihaljevic M, Miljevic C. Improving Current Treatments for Schizophrenia. Drug Dev Res. 2016 Nov; 77(7):357-367. Doi: 10.1002/ddr.21337.

Leucht S, Cipriani A, Spineli L et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia. A multiple-treatments meta-analysis. The Lancet. 2013; 382:951–962. Doi: 10.1016/S0140-6736(13)60733-3.

Nikolić-Kokić A, Tatalović N, Miljević Č et al. Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. Int J Mol Sci. 2022 Nov 8; 23(22):13698. Doi: 10.3390/ijms232213698.

Ostuzzi G, Mazzi MA, Terlizzi S et al. STAR Network Investigators. Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy. PLoS One. 2018 Aug 2; 13(8):e0201371. Doi: 10.1371/journal.pone.0201371.

Miljević ČD, Vuković PG, Munjiza-Jovanović A. Clinical challenges in the dosing and titration of cariprazine. Front Psychiatry. 2024; 15:1427482. Doi: 10.3389/fpsyt.2024.1427482.

Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. 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.

Miljević C, Nikolić-Kokić A, Saicić ZS et al. Correlation analysis confirms differences in antioxidant defence in the blood of types I and II schizophrenic male patients treated with anti-psychotic medication. Psychiatry Res. 2010; 178(1):68-72. Doi: 10.1016/j.psychres.2008.10.038.

Miljević ČD, Nikolić-Kokić A, Blagojević D et al. Association between neurological soft signs and antioxidant enzyme activity in schizophrenic patients. Psychiatry Res. 2018; 269:746-752. Doi: 10.1016/j.psychres.2018.09.009.

Kishimoto T, Nitta M, Borenstein M et al. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013; 74(10):957–965. Doi: 10.4088/JCP.13r08440.

Patel RS, Tankersley WE. Real-world Effectiveness of Long-Acting Injectable (LAI) Antipsychotics to Reduce 90-day and Annual Readmission in Psychotic Disorders: Insights from a State Psychiatric Hospital. CNS Spectrums. 2021; 1–19. Doi10.1017/s109285292100050x.

Keepers GA, Fochtmann LJ, Anzia JM et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020; 177(9):868–872. Doi10.1176/appi. ajp.2020.177901.

Correll CU, Citrome L, Haddad PM et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016; 77(Suppl 3):1–24. Doi: 10.4088/JCP.15032su1.

Citrome L, Belcher E, Stacy S, Suett M, Mychaskiw M, Salinas GD. Management of schizophrenia with long-acting injectable antipsychotic medications: an assessment of the educational needs of clinicians. Neuropsychiatr Dis Treat. 2022; 18:111–23 Doi: 10.2147/NDT.S326299.

Álamo C. Risperidone ISM as a New Option in the Clinical Management of Schizophrenia: A Narrative Review. Adv Ther. 2022; 39(11):4875-4891. Doi: 10.1007/s12325-022-02299-8. Epub 2022 Sep 1.

Jašović-Gašić M, Ivković M, Damjanović A, Paunović V. Nove mogućnosti u dugotrajnoj terapiji shozofrenih pacijenata: dugodelujući risperidone (rispolept consta). Engrami 2004; 26(12): 107-110.

Knox ED, Stimmel GL. Clinical review of a long-acting, injectable formulation of risperidone. Clinical Therapeutics. 2004; 26(12):1994–2002. Doi: 10.1016/j.clinthera.2004.12.009.

Gefvert O, Eriksson B, Persson P et al.Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia. Int J Neuropsychopharmacol. 2005; 8(1):27-36. Doi: 10.1017/S1461145704004924.

Lasser RA, Bossie CA, Gharabawi GM, Baldessarini RJ. Clinical improvement in 336 stable chronically psychotic patients changed from oral to long-acting risperidone: a 12-month open trial. Int J Neuropsychopharmacol. 2005; 8(3):427-38. Doi: 10.1017/S1461145705005225.

Malempati RN, Bond DJ, Yatham LN. Depot risperidone in the outpatient management of bipolar disorder: a 2-year study of 10 patients. Int Clin Psychopharmacol. 2008; 23(2):88-94. Doi: 10.1097/YIC.0b013e3282f2b4c5.

Keith S. Use of long-acting risperidone in psychiatric disorders: focus on efficacy, safety and cost-effectiveness. Expert Rev Neurother. 2009; 9(1):9-31. Doi: 10.1586/14737175.9.1.9.

Correll CU, Litman RE, Filts Y et al. Efficacy and safety of once-monthly Risperidone ISM in schizophrenic patients with an acute exacerbation. NPJ Schizophr. 2020; 6(1):37 Doi: 10.1038/s41537-020-00127-y.

Clark I, Taylor D. Newer formulations of risperidone: role in the management of psychotic disorders. CNS Drugs. 2020; 34(8):841–52 Doi: 10.1007/s40263-020-00735-3.

Anta L, Llaudo´ J, Ayani I, Martı´nez J, Litman RE, Gutierro I. A phase II study to evaluate the pharmacokinetics, safety, and tolerability of Risperidone ISM multiple intramuscular injections once every 4 weeks in patients with schizophrenia. Int Clin Psychopharmacol. 2018; 33(2):79–87 Doi: 10.1097/YIC.0000000000000203.

Llaudó J, Anta L, Ayani I, Martínez J et al. Phase I, open-label, randomized, parallel study to evaluate the pharmacokinetics, safety, and tolerability of one intramuscular injection of risperidone ISM at different dose strengths in patients with schizophrenia or schizoaffective disorder (PRISMA-1). Int Clin Psychopharmacol. 2016; 31(6):323-31. Doi: 10.1097/YIC.0000000000000139.

Bioque M, Bernardo M. The current data on the 3-month paliperidone palmitate formulation for the treatment of schizophrenia. Expert Opin Pharmacother. 2018; 19(14):1623-1629. Doi: 10.1080/14656566.2018.1515915.

Parellada E, Bioque M, Serrano M et al. An open-treatment sixweek study of the clinical effectiveness of paliperidone palmitate in schizophrenia: data from acute units in Spain (SHADOW study). Int J Psychiatry Clin Pract. 2018; 22(3):191–199 Doi: 10.1080/13651501.2017.1404112.

Janssen-Cilag International NV. Sažetak karakteristika leka – Xeplion® (paliperidonpalmitat) [Internet]. Beograd: Janssen; 2024 [cited 2025 May 13]. Available from: https://static.janssen-emea.com/sites/default/files/Serbia/SMPC/RS-PL-0047.pdf

Chue P, & Chue J. . A review of paliperidone palmitate. Expert Review of Neurotherapeutics,.2012;12(12):1383–1397. Doi: 10.1586/ern.12.137.

European Medicines Agency. European public assessment report [Internet]. 2018 [cited 2025 May 13]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004066/human_med_001829.jsp&mid=WC0b01ac058001d124.

Ravenstijn P, Remmerie B, Savitz A et al. Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: a phase-1, single-dose, randomized, open-label study. J Clin Pharmacol. 2016; 56(3):330–339 Doi: 10.1002/jcph.597.

Gonzalez-Rodriguez A, Catalan R, Penades R et al. Profile of paliperidone palmitate once-monthly long-acting injectable in the management of schizophrenia: long-term safety, efficacy, and patient acceptability - a review. Patient Prefer Adherence. 2015; 9:695–706 Doi: 10.1136/bcr-2015-212149.

Schreiner A, Bergmans P, Cherubin P et al. A prospective flexibledose study of paliperidone palmitate in nonacute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents. Clin Ther. 2014; 36(10):1372–1388 Doi: 10.1016/j.clinthera.2014.08.014.

Emsley R, Parellada E, Bioque M, Herrera B, Hernando T, García-Dorado M. Real-world data on paliperidone palmitate for the treatment of schizophrenia and other psychotic disorders: a systematic review of randomized and nonrandomized studies. Int Clin Psychopharmacol. 2018; 33(1):15-33. Doi: 10.1097/YIC.0000000000000195.

Savitz AJ, Xu H, Gopal S et al. Paliperidone palmitate 3-month treatment results in symptomatic remission in patients with schizophrenia: a randomized, multicenter, double-blind, and noninferiority study. Int Clin Psychopharmacol. 2017; 32(6):329–336 Doi: 10.1097/YIC.0000000000000190.

Citrome L. Paliperidone palmitate - review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication. Int J Clin Pract. 2010; 64(2):216-39. Doi: 10.1111/j.1742-1241.2009.02240.x.

Berwaerts J, Liu Y, Gopal S, et al. Efficacy and Safety of the 3-month formulation of paliperidone palmitate vs placebo for relapse prevention of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2015; 72(8):830–839 Doi: 10.1001/jamapsychiatry.2015.0241.

Laux G, Heeg B, van Hout BA, Mehnert A. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany. Pharmacoeconomics. 2005; 23 Suppl 1:49-61. Doi: 10.2165/00019053-200523001-00005.

Koshikawa Y, Takekita Y, Kato M, et al.The Comparative Effects of Risperidone Long-Acting Injection and Paliperidone Palmitate on Social Functioning in Schizophrenia: A 6-Month, Open-Label, Randomized Controlled Pilot Trial. Neuropsychobiology. 2016; 73(1):35-42. Doi: 10.1159/000442209.

Drug Information for Paliperidone Palmitate: Interview Form of Xeplion ® – Aqueous Suspension for IM Injection, ed 5. http://www. info.pmda.go.jp/go/pack/1179409G1025_ 1_07/. 2014.

Tost M, González-Rodríguez A, Aguayo R et al. Switching from risperidone to paliperidone palmitate in schizophrenia: Changes in social functioning and cognitive performance. Prog Neuropsychopharmacol Biol Psychiatry. 2023; 120:110619. Doi: 10.1016/j.pnpbp.2022.110619.

Janssen-Cilag International NV. Sažetak karakteristika leka – Trevicta® (paliperidonpalmitat) [Internet]. Beograd: Janssen; 2024 [cited 2025 May 13]. Available from: https://static.janssen-emea.com/sites/default/files/Serbia/SMPC/RS-PL-0041.pdf

Correll CU, Kim E, Sliwa JK, et al.Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview. CNS Drugs. 2021; 35(1):39-59. Doi: 10.1007/s40263-020-00779-5.

Maini K, Gould H, Hicks J et al. Aripiprazole Lauroxil, a Novel Injectable Long-Acting Antipsychotic Treatment for Adults with Schizophrenia: A Comprehensive Review. Neurol Int. 2021;13(3):279-296. Doi: 10.3390/neurolint13030029.

Peters L, Dyer M, Schroeder E, D'Souza MS. Invega Hafyera (Paliperidone Palmitate): Extended-Release Injectable Suspension for Patients With Schizophrenia. J Pharm Technol. 2023; 39(2):88-94. Doi: 10.1177/87551225231153541.