Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News and Commentary
  • Published:

Changes for clozapine monitoring in the United States

Molecular Psychiatry volume 21, pages 858–860 (2016)Cite this article

Subjects

Clozapine is a unique compound that is particularly effective for treatment-resistant schizophrenia (TRS). The use of clozapine is limited, however, due to the 0.8% risk of agranulocytosis,1 which necessitates a strict monitoring of neutrophil counts to detect early neutropenia and prevent progression to agranulocytosis. The US Food and Drug Administration (FDA) in 2015 allowed greater flexibility to continue or re-challenge clozapine in patients who have experienced neutropenia on clozapine.2 Lithium and granulocyte-colony stimulating factor (G-CSF) have been used as preventative therapies for patients with a history of clozapine-induced neutropenia upon clozapine re-challenge.

This compound was synthesized in 1959 shortly after the discovery of chlorpromazine in 1952.3 However, just as it was about to become more widely used, in September 1975 in Finland 4 months following the introduction of clozapine, 16 patients developed agranulocytosis, 8 of whom died as a result of infection.4

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Pirmohamed M, Park K . Mechanism of clozapine-induced agranulocytosis. CNS Drugs 1997; 7: 139–158.

    Article  CAS  Google Scholar 

  2. US Food and Drug and Administration (2015). FDA Drug Safety Communication: FDA modifies monitoring for neutropenia associated with schizophrenia medicine clozapine; approves new shared REMS program for all clozapine medicines. Available at http://www.fda.gov/Drugs/DrugSafety/ucm461853.htm.

  3. Crilly J . The history of clozapine and its emergence in the US market: a review and analysis. Hist Psychiatry 2007; 18: 39–60.

    Article  Google Scholar 

  4. Idänpään-Heikkilä J, Alhava E, Olkinuora M, Palva I . Letter: clozapine and agranulocytosis. Lancet 1975; 2: 611.

    Article  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. Honigfield G . Effects of the clozapine national registry system on incidence of deaths related to agranulocytosis. Psychiatr Serv 1996; 47: 52–56.

    Article  Google Scholar 

  7. Sriretnakumar V, Huang E, Muller D . Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update. Expert Opin Drug Metab Toxicol 2015; 11: 1709–1731.

    Article  CAS  Google Scholar 

  8. Flanagan RJ, Dunk L . Haematological toxicity of drugs used in psychiatry. Hum Psychopharmacol 2008; 23: 27–41.

    Article  CAS  Google Scholar 

  9. Comacchio C, Dusi N, Lasalvia A . Successful use of single doses of granulocyte-colony stimulating factor (G-CSF) in the treatment of late-onset agranulocytosis associated with clozapine in a patient with treatment-resistant schizophrenia: a case report. J Clin Psychopharmacol 2016; 36: 173–174.

    Article  Google Scholar 

  10. Rajagopal S . Clozapine, agranulocytosis, and benign ethnic neutropenia. Postgrad Med J 2005; 81: 545–546.

    Article  CAS  Google Scholar 

  11. Manu P, Sarpal D, Muir O, Kane JM, Correll CU . When can patients with potentially life-threatening adverse effects be rechallenged with clozapine? A systematic review of the published literature. Schizophr Res 2012; 134: 180–186.

    Article  Google Scholar 

  12. Gerson SL, Gullion G, Yeh HS, Masor C . Granulocyte colony-stimulating factor for clozapine-induced agranulocytosis. Lancet 1992; 340: 1097.

    Article  CAS  Google Scholar 

  13. Hägg S, Rosenius S, Spigset O . Long-term combination treatment with clozapine and filgrastim in patients with clozapine-induced agranulocytosis. Int Clin Psychopharmacol 2003; 18: 173–174.

    Article  Google Scholar 

  14. Hazewinkel AW, Bogers JP, Giltay EJ . Add-on filgrastim during clozapine rechallenge unsuccessful in preventing agranulocytosis. Gen Hosp Psychiatry 2013; 35: 576.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. SAHMRI- Mind and Brain Research Fellow, Adelaide, SA, Australia

    T Bastiampillai

  2. Mental Health Strategy, SA Health, Govt. of South Australia, Adelaide, SA, Australia

    T Bastiampillai

  3. Department of Psychiatry, Flinders University, Adelaide, SA, Australia

    T Bastiampillai

  4. Department of Psychiatry, Flinders Medical Centre, Bedford Park, Adelaide, SA, Australia

    A Gupta

  5. Department of Psychiatry, The University of Hong Kong, Hong Kong

    S K W Chan

  6. The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong

    S K W Chan

  7. Discipline of Psychiatry, School of Medicine, Flinders University, Adelaide, SA, Australia

    S Allison

Authors
  1. T Bastiampillai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S K W Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Allison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Bastiampillai.

Ethics declarations

Competing interests

The author declares no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bastiampillai, T., Gupta, A., Chan, S. et al. Changes for clozapine monitoring in the United States. Mol Psychiatry 21, 858–860 (2016). https://doi.org/10.1038/mp.2016.66

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2016.66

Search

Advanced search

Quick links