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Pathway to Clozapine Use: A Comparison Between a Patient Cohort from New Zealand and a Cohort from the United Kingdom

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Abstract

Background and Objective

Clozapine has been available since the early 1990s. Studies continue to demonstrate its superior efficacy in treatment-resistant schizophrenia. Despite this, numerous studies show under-utilisation, delayed access and reluctance by psychiatrists to prescribe clozapine. This retrospective cross-sectional study compared the prescribing of clozapine in two adult cohorts under the care of large public mental health services in Auckland (New Zealand) and Birmingham (United Kingdom) on 31 March 2007.

Method

Time from first presentation to clozapine initiation, prior antipsychotics trialled and antipsychotic co-prescribing were compared. Data included demographics, psychiatric diagnosis, co-morbid conditions, year of first presentation, admissions and pharmacological treatment (clozapine dose, start date, prior antipsychotics, co-prescribed antipsychotic).

Results

Overall, 664 people were prescribed clozapine (402 Auckland; 262 Birmingham); mean daily dose of 384 mg (Auckland) and 429 mg (Birmingham). 53 % presented after 1990 and the average duration of time before starting clozapine was significantly longer in the Birmingham cohort (6.5 vs. 5.3 years) but this reduced in both cohorts to a 1-year mean in those presenting within the last 3 years. The average number of antipsychotics trialled pre-clozapine for those presenting since 1990 was significantly higher in the Birmingham cohort (4.3 vs. 3.1) but in both cohorts this similarly reduced in those presenting within the last 3 years. Antipsychotic co-prescribing was significantly higher in the Birmingham cohort (22.9 vs. 10.7 %).

Conclusions

There is evidence that access to clozapine has improved over time in both cohorts, with a reduction in the duration between presentation and initiation of clozapine and number of different antipsychotics trialled pre-clozapine. These are very positive findings in terms of optimising outcomes with clozapine and are possibly due to the impact of guideline recommendations, increasing clinician, consumer and carer knowledge, and experience with clozapine and funding changes.

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References

  1. Leucht S, Corves C, Arbter D, et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009;373(9657):31–41.

    Article  CAS  PubMed  Google Scholar 

  2. Leucht S, Komossa K, Rummel-Kluge C, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009;166(2):152–63.

    Article  PubMed  Google Scholar 

  3. National Collaborating Centre for Mental Health. Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care. Clinical guideline, vol. 82. London: National Institute for Health and Clinical Excellence; 2009. http://www.nice.org.uk/CG82. Accessed 17 Dec 2012.

  4. Royal Australian and New Zealand College of Psychiatrists. Clinical Practice Guidelines Team for Schizophrenia and Related Disorders. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders. Aust N Z J Psychiatry. 2005;39(1–2):1–30.

    Google Scholar 

  5. Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009;374(9690):620–7. doi:10.1016/S0140-6736(09)60742-X.

    Article  PubMed  Google Scholar 

  6. Walker AM, Lanza LL, Arellano F, et al. Mortality in current and former users of clozapine. Epidemiology. 1997;8(6):671–7.

    Article  CAS  PubMed  Google Scholar 

  7. Kerwin R. When should clozapine be initiated in schizophrenia? Some arguments for and against earlier use of clozapine. CNS Drugs. 2007;21(4):267–78.

    Article  CAS  PubMed  Google Scholar 

  8. Agid O, Foussias G, Singh S, et al. Where to position clozapine: re-examining the evidence. Can J Psychiatry. 2010;55(10):677–84.

    PubMed  Google Scholar 

  9. Si T, Zhang Y, Shu L, et al. Use of clozapine for the treatment of schizophrenia: findings of the 2006 research on the China Psychotropic Prescription Studies. Clin Psychopharmacol Neurosci. 2012;10(2):99–104.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Downs J, Zinkler M. Clozapine: national review of postcode prescribing. Psychiatr Bull. 2007;31(10):384–7. doi:10.1192/pb.bp.106.013144.

    Article  Google Scholar 

  11. Sernyak MJ, Rosenheck RA. Antipsychotic use in the treatment of outpatients with schizophrenia in the VA from fiscal years 1999 to 2006. Psychiatr Serv. 2008;59(5):567–9.

    Article  PubMed  Google Scholar 

  12. Nielsen J, Røge R, Schjerning O, et al. Geographical and temporal variations in clozapine prescription for schizophrenia. Eur Psychopharmacol. 2012;22(11):818–24.

    CAS  Google Scholar 

  13. Hermes E, Rosenheck R. Choice of randomization to clozapine versus other second generation antipsychotics in the CATIE schizophrenia trial. J Psychopharmacol. 2012;26(9):1194–200.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Malalagama G, Bastiampillai T, Dhillon R. Clozapine use in Australia. Australas Psychiatry. 2011;19(2):175.

    Article  PubMed  Google Scholar 

  15. Wheeler A, Humberstone V, Robinson G. Outcomes for schizophrenia patients with clozapine treatment: how good does it get? J Psychopharmacol. 2009;23(8):957–65.

    Article  CAS  PubMed  Google Scholar 

  16. Wheeler A, Humberstone V, Robinson E, et al. Impact of audit and feedback on antipsychotic prescribing in schizophrenia. J Eval Clin Pract. 2009;15(3):441–50.

    Article  PubMed  Google Scholar 

  17. Wheeler AJ. Treatment pathway and patterns of clozapine prescribing for schizophrenia in New Zealand. Ann Pharmacother. 2008;42(6):852–60.

    Article  CAS  PubMed  Google Scholar 

  18. Taylor DM, Young C, Paton C. Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review. J Clin Psychiatry. 2003;64(1):30–4.

    Article  PubMed  Google Scholar 

  19. Nielsen J, Dahm M, Lublin H, et al. Psychiatrists attitude towards and knowledge of clozapine treatment. J Psychopharmacol. 2010;24(7):965–71. doi:10.1177/0269881108100320.

    Article  CAS  PubMed  Google Scholar 

  20. Cirulli G. Clozapine prescribing in adolescent psychiatry: survey of prescribing practice in in-patient units. Psychiatr Bull. 2005;29:377–80.

    Article  Google Scholar 

  21. Meltzer HY. Clozapine: balancing safety with superior antipsychotic efficacy. Clin Schizophr Relat Psychoses. 2012;6(3):134–44.

    Article  PubMed  Google Scholar 

  22. Falzer PR, Garman DM. Optimizing clozapine through clinical decision making. Acta Psychiatr Scand. 2012;126(1):47–58.

    Article  CAS  PubMed  Google Scholar 

  23. Farooq S, Taylor M. Clozapine: dangerous orphan or neglected friend? Br J Psychiatry. 2011;198(4):247–9.

    Article  PubMed  Google Scholar 

  24. Mortimer AM. Using clozapine in clinical practice. Adv Psychiatr Treat. 2011;17:256–65.

    Article  Google Scholar 

  25. Mistry H, Osborn D. Underuse of clozapine in treatment-resistant schizophrenia. Adv Psychiatr Treat. 2011;17(4):250–5.

    Article  Google Scholar 

  26. Nielsen J, Damkier P, Lublin H, et al. Optimizing clozapine treatment. Acta Psychiatr Scand. 2011;123(6):411–22. doi:10.1111/j.1600-0447.2011.01710.x.

    Article  CAS  PubMed  Google Scholar 

  27. National Collaborating Centre for Mental Health. Schizophrenia: core interventions in the treatment of schizophrenia in primary and secondary care. Clinical guideline 1. London: National Institute for Clinical Excellence; 2002.

  28. McGorry P, Killackey E, Elkins K, et al. Summary Australian and New Zealand clinical practice guideline for the treatment of schizophrenia 2003. Australas Psychiatry. 2003;11(2):136–47.

    Article  Google Scholar 

  29. Walker RA, Martin S. Demographic profile for Waitemata District Health Board: an analysis of 2006 census. Auckland: Waitemata District Health Board; 2007.

    Google Scholar 

  30. Birmingham and Solihull Mental Health NHS Foundation Trust. About us. Birmingham. http://www.bsmhft.nhs.uk/about-us/. Accessed 19 Nov 2012.

  31. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.

    Google Scholar 

  32. Baldessarini RJ, Cohen BM, Teicher MH. Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses. Arch Gen Psychiatry. 1988;45(1):79–91.

    Article  CAS  PubMed  Google Scholar 

  33. Humberstone V, Wheeler A, Lambert T. An audit of outpatient antipsychotic usage in the three health sectors of Auckland, New Zealand. Aust N Z J Psychiatry. 2004;38(4):240–5.

    PubMed  Google Scholar 

  34. Harrison J, Janlov M, Wheeler AJ. Patterns of clozapine prescribing in a mental health service in New Zealand. Pharm World Sci. 2010;32(4):503–11.

    Article  PubMed  Google Scholar 

  35. Howes OD, Vergunst F, Gee S, et al. Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry. 2012;201(6):481–5. doi:10.1192/bjp.bp.111.105833.

    Article  PubMed  Google Scholar 

  36. McIlwain ME, Harrison J, Wheeler AJ, et al. Pharmacotherapy for treatment-resistant schizophrenia. Neuropsychiatry. 2011;7:135–49.

    CAS  Google Scholar 

  37. Fleischhacker WW, Heikkinen ME, Olie J-P, et al. Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmcol. 2010;13(8):1115–25.

    Article  CAS  Google Scholar 

  38. Croissant B, Hermann D, Olbrich R. Reduction of side effects by combining clozapine with amisulpride: case report and short review of clozapine-induced hypersalivation-a case report. Pharmacopsychiatry. 2005;38(1):38–9.

    Article  CAS  PubMed  Google Scholar 

  39. Procyshyn RM, Honer WG, Wu TKY, et al. Persistent antipsychotic polypharmacy and excessive dosing in the community psychiatric treatment setting: a review of medication profiles in 435 Canadian outpatients. J Clin Psychiatry. 2010;71(5):566–73.

    Article  CAS  PubMed  Google Scholar 

  40. Hodge K, Jespersen S. Side-effects and treatment with clozapine: a comparison between the views of consumers and their clinicians. Int J Ment Health Nurs. 2008;17:2–8.

    Article  PubMed  Google Scholar 

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Acknowledgments

Thanks are due to the mental health services and staff in Birmingham and Auckland. Thanks also go to Minna Janlov, Priya Radia, Ramesh Rana and Nigel Barnes for their support and Peter Walsh who reviewed the manuscript.

Declaration of Interests

AW has received research funding, lecturing and/or conference support from Janssen-Cilag, Eli Lilly, AstraZeneca, Roche Diagnostics, Novartis, Pfizer, Sanofi-Aventis, Douglas Pharmaceuticals and Wyeth. C.F has received consultancy, conference support and/or lecture fees from Lundbeck, Roche, AstraZeneca, BMS-Otsuka, Eli Lilly, Janssen-Cilag, Lundbeck, Merz, Roche, Schering-Plough/MSD and Servier. JF has no conflicts of interest to declare.

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Authors and Affiliations

  1. Griffith Health Institute, Griffith University, University Drive, Brisbane, 4131, Australia

    Amanda J. Wheeler

  2. Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

    Amanda J. Wheeler & Jeff Harrison

  3. Psychiatric Pharmacy Programmes, Life and Health Sciences, School of Pharmacy, Aston University, Birmingham, UK

    Celia L. Feetam

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  1. Amanda J. Wheeler
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Correspondence to Amanda J. Wheeler.

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Wheeler, A.J., Feetam, C.L. & Harrison, J. Pathway to Clozapine Use: A Comparison Between a Patient Cohort from New Zealand and a Cohort from the United Kingdom. Clin Drug Investig 34, 203–211 (2014). https://doi.org/10.1007/s40261-013-0166-x

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