Effectiveness and Safety Comparison of Clozapine-Haloperidol with Clozapine-Risperidon Regimen in Schizophrenia Inpatients at Prof. Dr. Soerojo Magelang Mental Hospital

https://doi.org/10.22146/jmpf.96818

Maria Sri Ayu Mustikawati(1), Bambang Hastha Yoga Legowo Budiman(2), Zullies Ikawati(3*)

(1) Master Program of Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta
(2) Department of Psychiatry Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
(3) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Background: Schizophrenia treatment uses drugs from the antipsychotic group. Antipsychotics combination of clozapine-haloperidol and clozapine-risperidone are widely used in schizophrenia inpatients. Clozapine is often used in combination with haloperidol and risperidone (high-potency antipsychotic) to enhance the blockade of D2 receptors.

Objectives: To compare the effectiveness and safety of the clozapine-haloperidol regimen with clozapine-risperidone used by schizophrenia inpatients.

Methods: The research design was retrospective cohort observational. Data collection based on medical records of inpatients diagnosed with schizophrenia at Prof. Dr. Soerojo Magelang Mental Hospital in January 2021 - June 2023. The subjects were 142 people (71 people in both groups). Effectiveness was assessed by the difference in pre and post-PANSS-EC scores, as well as clinical improvement through the final PANSS-EC score. Meanwhile, safety was evaluated based on the incidence of drug side effects. The data was then analyzed statistically.

Results: The average PANSS-EC score decrease was 10 ± 5.53 in the clozapine-haloperidol group and 11 ± 5.70 in clozapine-risperidone group. Nonetheless, there was no meaningful contrast between them in terms of PANSS-EC difference (p=0.326), or improvement in clinical condition by the final PANSS-EC score (p=0.111). Also, there was no meaningful distinction in the incidence of adverse drug events (p=0.422).  However, extrapyramidal syndrome, the most frequent side effect (18 out of 40 cases), had a significant difference with the clozapine-haloperidol group having the most cases (p=0.044).

Conclusion: Both regimens are interchangeable in clinical practice. But clozapine-risperidone is better tolerated regarding extrapyramidal side effects.


Keywords


Antipsychotic combination; safety; schizophrenia; therapeutic effectiveness

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References

  1. Marder SR, Cannon TD. Schizophrenia. New England Journal of Medicine. 2019;381(18):1753-1761. doi:10.1056/nejmra1808803
  2. Peritogiannis V, Ninou A, Samakouri M. Mortality in Schizophrenia-Spectrum Disorders: Recent Advances in Understanding and Management. Healthcare (Switzerland). 2022;10(12). doi:10.3390/healthcare10122366
  3. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9(2):137-150. doi:10.1016/S2215-0366(21)00395-3
  4. Kementerian Kesehatan RI. InfoDATIN: Situasi Kesehatan Jiwa Di Indonesia.; 2019.
  5. Kim W, Jang SY, Chun SY, Lee TH, Han KT, Park EC. Mortality in schizophrenia and other psychoses: Data from the south korea national health insurance cohort, 2002-2013. J Korean Med Sci. 2017;32(5):835-842. doi:10.3346/jkms.2017.32.5.835
  6. DiPiro JT, Yee GC, Posey LM, Haines ST, Nolin TD, Ellingrod V. Pharmacotherapy: A Pathophysiologic Approach. 11th Edition. McGraw Hill; 2020.
  7. Lähteenvuo M, Tiihonen J. Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations. Drugs. 2021;81(11):1273-1284. doi:10.1007/s40265-021-01556-4
  8. Purwandityo AG, Febrianti Y, Sari CP, Ningrum VDA, Sugiyarto OP. Pengaruh Antipsikotik terhadap Penurunan Skor The Positive and Negative Syndrome Scale-Excited Component. Jurnal Farmasi Klinik Indonesia. 2018;7(1):19-29. doi:10.15416/ijcp.2018.7.1.19
  9. Nucifora FC, Mihaljevic M, Lee BJ, Sawa A. Clozapine as a Model for Antipsychotic Development. Neurotherapeutics. 2017;14(3):750-761. doi:10.1007/s13311-017-0552-9
  10. Freudenreich O, Goff DC. Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current combinations. Acta Psychiatr Scand. 2002;106:323-330. doi:10.1034/j.1600-0447.2002.01331.x
  11. Kapur S, Roy P, Daskalakis J, Remington G, Zipursky R. Increased Dopamine D2 Receptor Occupancy and Elevated Prolactin Level Associated With Addition of Haloperidol to Clozapine. Am J Psychiatry. 2001;158(2):311-314. doi:10.1176/appi.ajp.158.2.311
  12. Styawan Y, Suprapti S, Utami AW. Pola Penggunaan Obat Antipsikotik pada Pasien Skizofrenia di Seluruh Puskesmas Kota Yogyakarta. INPHARNMED Journal (Indonesian Pharmacy and Natural Medicine Journal). 2022;6(1):10-17. doi:10.21927/inpharnmed.v6i1.2244
  13. Meilina NA, Cahaya N, Putra AMP. Analisis Trend Peresepan Golongan Antipsikotika Tipikal dan Atipikal di Tiga Puskesmas di Kota Banjarmasin Periode 2019-2021. Jurnal Sains dan Kesehatan. 2022;4(4):393-400. doi:10.25026/jsk.v4i4.1269
  14. Ranti I, Octaviany AF, Kinanti S. Analisis Efektivitas Terapi dan Biaya antara Haloperidol Kombinasi dengan Risperidon Kombinasi pada Terapi Skizofrenia Fase Akut. Mutiara Medika. 2015;15(1):57-64.
  15. Kuwilsky A, Krumm B, Englisch S, Dressing H, Zink M. Long-term efficacy and tolerability of clozapine combined with ziprasidone or risperidone. Pharmacopsychiatry. 2010;43(6):216-220. doi:10.1055/s-0030-1254089
  16. Cipriani A, Accordini S, Nosè M, et al. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: A 12-month, randomized, naturalistic trial. J Clin Psychopharmacol. 2013;33(4):533-537. doi:10.1097/JCP.0b013e318296884f
  17. Barber S, Olotu U, Corsi M, Cipriani A. Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia. Cochrane Database of Systematic Reviews. 2017;2017(3). doi:10.1002/14651858.CD006324.pub3
  18. Sadock BJ., Sadock VA., Ruiz Pedro. Kaplan & Sadock’s Synopsis of Psychiatry : Behavioral Sciences/Clinical Psychiatry. Eleventh Edition. Wolters Kluwer; 2015.
  19. Khanna P, Suo T, Komossa K, et al. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews. 2014;(1). doi:10.1002/14651858.CD006569.pub5
  20. 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(9896):951-962. doi:10.1016/S0140-6736(13)60733-3
  21. Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. 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. The Lancet. 2019;394(10202):939-951. doi:10.1016/S0140-6736(19)31135-3
  22. Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first-and second-generation antipsychotics: A state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757-777. doi:10.2147/TCRM.S117321
  23. Seeman M V. Men and women respond differently to antipsychotic drugs. Neuropharmacology. 2020;163:1-10. doi:10.1016/j.neuropharm.2019.05.008
  24. Furukawa TA, Levine SZ, Tanaka S, et al. Initial Severity of Schizophrenia and Efficacy of Antipsychotics: Participant-level meta-analysis of 6 placebo-controlled studies. JAMA Psychiatry. 2015;72(1):14-21. doi:10.1001/jamapsychiatry.2014.2127
  25. Yoshida K, Takeuchi H. Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia. Behavioural Brain Research. 2021;402(113098). doi:10.1016/j.bbr.2020.113098
  26. Abdulah R, Siregar RF, Alfian SD. Analisis Efektivitas Biaya Penggunaan Kombinasi Antipsikotik pada Pasien Rawat Inap Skizofrenia. Jurnal Farmasi Klinik Indonesia. 2017;6(1):61-66. doi:10.15416/ijcp.2017.6.1.61



DOI: https://doi.org/10.22146/jmpf.96818

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