Korean Journal of Schizophrenia Research (대한조현병학회지)

Korean Society for Schizophrenia Research (대한조현병학회)
권호 표지
DOI QR코드

DOI QR Code

Current Status of Clozapine for Treatment-Resistant Schizophrenia

치료저항성 조현병에서 클로자핀 치료의 현황

  • Kim, Se Hyun (Department of Psychiatry, Seoul National University Hospital)
  • 김세현 (서울대학교병원 정신건강의학과)
  • Received : 2021.04.06
  • Accepted : 2021.04.23
  • Published : 2021.04.30
⟨ Previous Next ⟩

Abstract

Clozapine is the first and most effective atypical antipsychotic drug for treatment-resistant schizophrenia (TRS). After withdrawal of clozapine due to concerns of agranulocytosis, clozapine was reintroduced with a comprehensive safety monitoring system, the clozapine patient monitoring system (CPMS). The reintroduction was a response to the pressure from psychiatrists and patients with TRS and their families. Clozapine is still the best single agent for the treatment of TRS. However, approximately 30% of patients with TRS still show psychotic symptoms. In patients with clozapine-resistant schizophrenia (CRS), augmentation of other antipsychotic agents could be considered after a thorough evaluation of proper clozapine treatment. In this review, the status of clozapine in patients with TRS and CRS will be discussed.

Keywords

References

  1. Lee JS, Yun JY, Kang SH, Lee SJ, Choi JH, Nam B, et al. Korean Medication Algorithm for Schizophrenia 2019, Second Revision: Treatment of Psychotic Symptoms. Clin Psychopharmacol Neurosci 2020;18:386-394. https://doi.org/10.9758/cpn.2020.18.3.386
  2. Taylor DM. Clozapine for Treatment-Resistant Schizophrenia: Still the Gold Standard? CNS Drugs 2017;31:177-180. https://doi.org/10.1007/s40263-017-0411-6
  3. Ban TA. Fifty years chlorpromazine: a historical perspective. Neuropsychiatr Dis Treat 2007;3:495-500.
  4. Kuhn R. The treatment of depressive states with G 22355 (imipramine hydrochloride). Am J Psychiatry 1958;115:459-464. https://doi.org/10.1176/ajp.115.5.459
  5. Crilly J. The history of clozapine and its emergence in the US market: a review and analysis. Hist Psychiatry 2007;18:39-60. https://doi.org/10.1177/0957154X07070335
  6. Hippius H. A historical perspective of clozapine. J Clin Psychiatry 1999;60 Suppl 12:22-23. https://doi.org/10.4088/JCP.v60n0105
  7. Lee K. Treatment-Resistant Schizophrenia: Terminology and Clinical Features. Korean J Schizophr Res 2020;23:45-50. https://doi.org/10.16946/kjsr.2020.23.2.45
  8. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988;45:789-796. https://doi.org/10.1001/archpsyc.1988.01800330013001
  9. Wahlbeck K, Cheine M, Essali A, Adams C. Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. Am J Psychiatry 1999;156:990-999.
  10. Lewis S, Lieberman J. CATIE and CUtLASS: can we handle the truth? Br J Psychiatry 2008;192:161-163. https://doi.org/10.1192/bjp.bp.107.037218
  11. McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006;163:600-610. https://doi.org/10.1176/appi.ajp.163.4.600
  12. Samara MT, Dold M, Gianatsi M, Nikolakopoulou A, Helfer B, Salanti G, et al. Efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia: a network meta-analysis. JAMA Psychiatry 2016;73:199-210. https://doi.org/10.1001/jamapsychiatry.2015.2955
  13. Siskind D, McCartney L, Goldschlager R, Kisely S. Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. Br J Psychiatry 2016;209:385-392. https://doi.org/10.1192/bjp.bp.115.177261
  14. Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, 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. Lancet 2019;394:939-951. https://doi.org/10.1016/s0140-6736(19)31135-3
  15. Moller HJ, van Praag HM, Aufdembrinke B, Bailey P, Barnes TR, Beck J, et al. Negative symptoms in schizophrenia: considerations for clinical trials. Psychopharmacology 1994;115:221-228 https://doi.org/10.1007/BF02244775
  16. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, et al. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry 2002;159:1018-1028. https://doi.org/10.1176/appi.ajp.159.6.1018
  17. Han M, Zhang XY, Chen DC, Tan YL, Song CS, Yu YH, et al. Cognitive differences in schizophrenia on long-term treatments with clozapine, risperidone and typical antipsychotics. Int Clin Psychopharmacol 2015;30:89-95. https://doi.org/10.1097/YIC.0000000000000066
  18. Campana M, Falkai P, Siskind D, Hasan A, Wagner E. Characteristics and definitions of ultra-treatment-resistant schizophrenia-a systematic review and meta-analysis. Schizophr Res 2021;228:218-226. https://doi.org/10.1016/j.schres.2020.12.002
  19. Mouaffak F, Tranulis C, Gourevitch R, Poirier MF, Douki S, Olie JP, et al. Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia. Clin Neuropharmacol 2006;29:28-33. https://doi.org/10.1097/00002826-200601000-00009
  20. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry 2012;13:318-378. https://doi.org/10.3109/15622975.2012.696143
  21. Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, et al. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry 2017;174:216-229. https://doi.org/10.1176/appi.ajp.2016.16050503
  22. Kreyenbuhl J, Buchanan RW, Dickerson FB, Dixon LB, Schizophrenia Patient Outcomes Research T. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull 2010;36:94-103. https://doi.org/10.1093/schbul/sbp130
  23. Remington G, Addington D, Honer W, Ismail Z, Raedler T, Teehan M. Guidelines for the pharmacotherapy of schizophrenia in adults. Can J Psychiatry 2017;62:604-616. https://doi.org/10.1177/0706743717720448
  24. Sherwood M, Thornton AE, Honer WG. A quantitative review of the profile and time course of symptom change in schizophrenia treated with clozapine. J Psychopharmacol 2012;26:1175-1184. https://doi.org/10.1177/0269881112440513
  25. Subramaniam M, Ng C, Chong SA, Mahendran R, Lambert T, Pek E, et al. Metabolic differences between Asian and Caucasian patients on clozapine treatment. Hum Psychopharmacol 2007;22:217-222. https://doi.org/10.1002/hup.842
  26. Kim CE, Lee YH, Lee KH, Kang MH. Clozapine dosage and blood concentrations of Korean adult schizophrenic patients. J Korean Neuropsychiatr Assoc 2001;40:109-117.
  27. Lee ST, Ryu S, Nam HJ, Lee SY, Hong KS. Determination of pharmacokinetic properties of clozapine and norclozapine in Korean schizophrenia patients. Int Clin Psychopharmacol 2009;24:139-144. https://doi.org/10.1097/YIC.0b013e3283277627
  28. Kontaxakis VP, Ferentinos PP, Havaki-Kontaxaki BJ, Roukas DK. Randomized controlled augmentation trials in clozapine-resistant schizophrenic patients: a critical review. Eur Psychiatry 2005;20:409-415. https://doi.org/10.1016/j.eurpsy.2004.12.007
  29. Berk M, Fitzsimons J, Lambert T, Pantelis C, Kulkarni J, Castle D, et al. Monitoring the safe use of clozapine: a consensus view from Victoria, Australia. CNS Drugs 2007;21:117-127. https://doi.org/10.2165/00023210-200721020-00003
  30. Bartoli F, Crocamo C, Di Brita C, Esposito G, Tabacchi TI, Verrengia E, et al. Adjunctive second-generation antipsychotics for specific symptom domains of schizophrenia resistant to clozapine: a meta-analysis. J Psychiatr Res 2019;108:24-33. https://doi.org/10.1016/j.jpsychires.2018.11.005
  31. Siskind DJ, Lee M, Ravindran A, Zhang Q, Ma E, Motamarri B, et al. Augmentation strategies for clozapine refractory schizophrenia: A systematic review and meta-analysis. Aust N Z J Psychiatry 2018;52:751-767. https://doi.org/10.1177/0004867418772351
  32. Taylor DM, Smith L, Gee SH, Nielsen J. Augmentation of clozapine with a second antipsychotic a meta-analysis. Acta Psychiatr Scand 2012;125:15-24. https://doi.org/10.1111/j.1600-0447.2011.01792.x
  33. Galling B, Roldan A, Hagi K, Rietschel L, Walyzada F, Zheng W, et al. Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis. World Psychiatry 2017;16:77-89. https://doi.org/10.1002/wps.20387
  34. Wenthur CJ, Lindsley CW. Classics in chemical neuroscience: clozapine. ACS Chem Neurosci 2013;4:1018-1025. https://doi.org/10.1021/cn400121z
  35. Cipriani A, Accordini S, Nose M, Purgato M, Girlanda F, Tansella M, et al. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: a 12-month, randomized, naturalistic trial. J Clin Psychopharmacol 2013;33:533-537. https://doi.org/10.1097/JCP.0b013e318296884f
  36. Shiloh R, Zemishlany Z, Aizenberg D, Radwan M, Schwartz B, Dorfman-Etrog P, et al. Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study. Br J Psychiatry 1997;171:569-573. https://doi.org/10.1192/bjp.171.6.569
  37. Tiihonen J, Taipale H, Mehtala J, Vattulainen P, Correll CU, Tanskanen A. Association of antipsychotic polypharmacy vs monotherapy with psychiatric rehospitalization among adults with schizophrenia. JAMA Psychiatry 2019;76:499-507. https://doi.org/10.1001/jamapsychiatry.2018.4320
  38. Mossaheb N, Spindelegger C, Asenbaum S, Fischer P, Barnas C. Favourable results in treatment-resistant schizophrenic patients under combination of aripiprazole with clozapine. World J Biol Psychiatry 2010;11:502-505. https://doi.org/10.3109/15622970802269597
  39. Chang JS, Ahn YM, Park HJ, Lee KY, Kim SH, Kang UG, et al. Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2008;69:720-731. https://doi.org/10.4088/JCP.v69n0505
  40. Chang JS, Lee NY, Ahn YM, Kim YS. The sustained effects of aripiprazole-augmented clozapine treatment on the psychotic symptoms and metabolic profiles of patients with refractory schizophrenia. J Clin Psychopharmacol 2012;32:282-284. https://doi.org/10.1097/JCP.0b013e3182485871
  41. Bogers JP, Schulte PF, Van Dijk D, Bakker B, Cohen D. Clozapine underutilization in the treatment of schizophrenia: how can clozapine prescription rates be improved? J Clin Psychopharmacol 2016;36:109-111. https://doi.org/10.1097/JCP.0000000000000478
  42. Stroup TS, Gerhard T, Crystal S, Huang C, Olfson M. Geographic and clinical variation in clozapine use in the United States. Psychiatr Serv 2014;65:186-192. https://doi.org/10.1176/appi.ps.201300180
  43. Bachmann CJ, Aagaard L, Bernardo M, Brandt L, Cartabia M, Clavenna A, et al. International trends in clozapine use: a study in 17 countries. Acta Psychiatr Scand 2017;136:37-51. https://doi.org/10.1111/acps.12742
  44. Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med 1993;329:162-167. https://doi.org/10.1056/NEJM199307153290303
  45. Bastiampillai T, Gupta A, Chan SK, Allison S. Changes for clozapine monitoring in the United States. Mol Psychiatry 2016;21:858-860. https://doi.org/10.1038/mp.2016.66
  46. Kang BJ, Cho MJ, Oh JT, Lee Y, Chae BJ, Ko J. Long-term patient monitoring for clozapine-induced agranulocytosis and neutropenia in Korea: when is it safe to discontinue CPMS? Hum Psychopharmacol 2006;21:387-391. https://doi.org/10.1002/hup.779
  47. Schulte PF, Cohen D, Bogers JP, van Dijk D, Bakker B. A Dutch guideline for the use of clozapine. Aust N Z J Psychiatry 2010;44:1055-1056.
  48. Chandrasekaran PK. Agranulocytosis monitoring with clozapine patients: to follow guidelines or to attempt therapeutic controversies? Singapore Med J 2008;49:96-99.
  49. Nielsen J, Young C, Ifteni P, Kishimoto T, Xiang YT, Schulte PF, et al. Worldwide differences in regulations of clozapine use. CNS Drugs 2016;30:149-161. https://doi.org/10.1007/s40263-016-0311-1