Advertisement

The Role of Clozapine in Treatment-Resistant Schizophrenia

  • Kuppuswami Shivakumar
  • Shabbir Amanullah
  • Ranga Shivakumar
  • Kevin Saroka
  • Nicolas Rouleau
  • Nirosha J. Murugan
Chapter

Abstract

There have been various definitions of treatment-resistant schizophrenia recommended by practice guidelines and various clinical trials. No clear consensus exists for a single definition, but in general treatment resistance has been defined as an inadequate response to at least two different antipsychotic trials at the maximally tolerated dose. Clozapine is recommended for those patients with clinically significant positive symptoms after failure of two or more trials of antipsychotic medications. In this chapter, we will be discussing the side effects associated with clozapine treatment and also the role of the other professionals.

Keywords

Clozapine Agranulocytosis Myocarditis Urinary incontinence 

Notes

Disclosure Statement

“The authors have nothing to disclose”.

References

  1. 1.
    Herst L, Powell GI. Clozapine safe in the elderly? Aust N Z J Psychiatry. 1997;31:411–7.CrossRefPubMedGoogle Scholar
  2. 2.
    AA Pharma. Starting Patients on AA Clozapine. 2017.Google Scholar
  3. 3.
    Kilian JG, Kerr K, Lawrence C, Celermajer DS. Myocarditis and cardiomyopathy associated with clozapine. Lancet. 1999;354:1841–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Warner B, et al. Clozapine and sudden death. Lancet. 2000;355:842.CrossRefPubMedGoogle Scholar
  5. 5.
    Haas SJ, et al. Clozapine-associated myocarditis. Drug Saf. 2007;30(1):47–57.CrossRefPubMedGoogle Scholar
  6. 6.
    Ronaldson KJ, et al. A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls. Aust N Z J Psychiatry. 2011;45:458–65.CrossRefPubMedGoogle Scholar
  7. 7.
    Taylor D, Paton C, Shitij K. Prescribing guidelines in psychiatry: 12th edition. Wiley Blackwell: Oxford; 2015.Google Scholar
  8. 8.
    Magnani JW, Dec GW. Myocarditis. Circulation. 2006;113(6):876–90.CrossRefPubMedGoogle Scholar
  9. 9.
    Reinders J, et al. Clozapine-related myocarditis and cardiomyopathy in an Australian metropolitan psychiatric service. Aust N Z Psychiatry. 2004;38:915–22.CrossRefGoogle Scholar
  10. 10.
    Rostagno C, et al. Beta-blocker and angiotensin-converting enzyme inhibitor may limit certain cardiac adverse effects of clozapine. Gen Hosp Psychiatry. 2008;30:280–32.CrossRefPubMedGoogle Scholar
  11. 11.
    Floreani J, et al. Successful re-challenge with clozapine following development of clozapine-induced cardiomyopathy. Aust N Z J Psychiatry. 2008;42:747–849.PubMedGoogle Scholar
  12. 12.
    Roh S, et al. Cardiomyopathy associated with clozapine. Exp Clin Psychopharmacol. 2006;14:94–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Masopust J, et al. Repeated occurrence of clozapine-induced myocarditis in a patient with schizoaffective disorder and comorbid Parkinson’s disease. Neuro Endocrinol Lett. 2009;30:19–21.PubMedGoogle Scholar
  14. 14.
    Roaldson KJ, et al. Observations from 8 cases of clozapine rechallenge after development of myocarditis. J Clin Psychiatry. 2012;73:252–4.CrossRefGoogle Scholar
  15. 15.
    Fontana PG, Sumegi B. Association of Clozaril (clozapine) with cardiovascular toxicity. Novartis Pharmaceuticals Canada Inc. 2002.Google Scholar
  16. 16.
    Praharaj SK, Arora M, Gandotra S. Clozapine-induced sialorrhea: pathophysiology and management strategies. Psychopharmacology. 2006;185:265–73.CrossRefPubMedGoogle Scholar
  17. 17.
    Pacia SV, Devinsky O. Clozapine-related seizures: experience with 5629 patients. Neurology. 1994;44(12):2247–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Varma S. Clozapine– related EEG changes and seizures: dose and plasma level relationships. Ther Adv Psychopharmacol. 2011;1(2):47–66.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Williams AM, Park SH. Seizure associated with clozapine: incidence, etiology, and management. CNS Drugs. 2015;29:101–11.CrossRefPubMedGoogle Scholar
  20. 20.
    Hägg S, Spigset O, Söderström T. Association of venous thromboembolism and clozapine. Lancet. 2000;355:1155–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Axelsson S, Hägg S, Eriksson A, Lindahl T, Whiss P. In vitro effects of antipsychotics of human platelet adhesion and aggregation and plasma coagulation. Clin Exp Pharmacol Physiol. 2007;34:775–80.CrossRefPubMedGoogle Scholar
  22. 22.
    Hägg S, Jönsson A, Spigset O. Risk of venous thromboembolism due to antipsychotic drug therapy. Expert Opin Drug Saf. 2009;8:537–47.CrossRefPubMedGoogle Scholar
  23. 23.
    AA Pharma. Using clozapine today: treating schizophrenia from tertiary care to community care. 2017;1(1).Google Scholar
  24. 24.
    Carrizo E, Fernandez V, Connell L, Sandia I, Prieto D, Mogollon J, Valbuena D, et al. Extended release metformin for metabolic control assistance during prolonged clozapine administration: a 14 week, double-blind, parallel group, placebo-controlled study. Schizophr Res. 2009;113(1):19–26.CrossRefPubMedGoogle Scholar
  25. 25.
    Fuller MA, Borovicka MC, Jaskiw GE, Simon MR, Kown K, Konicki PE. Clozapine-induced urinary incontinence: incidence and treatment with ephedrine. J Clin Psychiatry. 1996;57(11):514.CrossRefPubMedGoogle Scholar
  26. 26.
    Freudenreich O, McEvoy J. Guidelines for prescribing clozapine in schizophrenia. UpToDate. Retrieved from: https://www.uptodate.com/contents/guidelines-for-prescribing-clozapine-in-schizophrenia.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Kuppuswami Shivakumar
    • 1
  • Shabbir Amanullah
    • 2
  • Ranga Shivakumar
    • 1
  • Kevin Saroka
    • 1
  • Nicolas Rouleau
    • 3
  • Nirosha J. Murugan
    • 4
  1. 1.Department of PsychiatryNorthern Ontario School of Medicine Psychiatry DepartmentSudburyCanada
  2. 2.University of Western OntarioWoodstock General Hospital University of Western OntarioWoodstockCanada
  3. 3.Department of Biomedical Engineering, Initiative for Neural ScienceDisease and Engineering (INScide) at Tufts University, Science and Engineering Complex (SEC)MedfordUSA
  4. 4.Allen Discovery Center at Tufts; Tufts Center for Regenerative and Developmental BiologyScience and Engineering Complex (SEC)MedfordUSA

Personalised recommendations