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OJHAS Vol. 11 Issue 1:
(Jan-Mar 2012) |
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| Prevalence
& Prescription: Prescribing Practices of Clozapine in Australia
between 2005 & 2010 |
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Shae-Leigh C. Vella, Nagesh B. Pai,
Graduate School of Medicine, University of Wollongong, New South Wales,
Australia 2522. |
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Address for Correspondence |
Graduate School of Medicine,
University of Wollongong,
New South Wales,
Australia 2522.
E-mail:
vella@uow.edu.au |
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Vella SC, Pai NB. Prevalence
& Prescription: Prescribing Practices of Clozapine in Australia
between 2005 & 2010. Online J Health Allied Scs.
2012;11(1):6 |
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Submitted: Jan 3,
2012;
Accepted: Mar 27, 2012; Published: Apr 15, 2012 |
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| Abstract: |
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Clozapine is an anti-psychotic used to treat refractory schizophrenia.
This study reviews the rates of clozapine prescription for refractory
schizophrenia in a region of Australia and compares the prescribing
patterns to the estimated prevalence rates of refractory schizophrenia
in the region. Utilising a pharmacoepidemiological approach; the results
indicated that only 8.4% of the individuals estimated to be suffering
from refractory schizophrenia in the region were prescribed clozapine
between 2005 and 2010, with only 4.1% continuing clozapine to the conclusion
of the study. In conclusion it is evident that clozapine is widely
under-prescribed in this area of Australia.
Key Words:
Clozapine; Treatment-resistant schizophrenia; Prevalence
rates; Australia
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Schizophrenia
is a chronic and debilitating mental disorder that afflicts approximately
1% of the population worldwide.(1) Schizophrenia is primarily treated
through the use of pharmacological treatments. However not all patients
who suffer from schizophrenia respond well to pharmacological interventions.
Approximately 30% of individuals who suffer from schizophrenia have
a poor response to typical or novel atypical treatments.(2,3) That
is these patients suffer from treatment-resistant or refractory schizophrenia.
Clozapine
an atypical or second generation anti-psychotic treatment has been proven
to be extremely effective in the treatment of refractory schizophrenia.(2,4,5) Moreover clozapine is the only anti-psychotic treatment that
is endorsed to treat refractory schizophrenia.(6) Specifically Wheeler
et al (5) in a large naturalistic study found that continued clozapine
treatment lead to improved functional and clinical outcomes. That is
patients made improvements in independent living and vocational activities
coupled with a reduction in the need for compulsory treatment and hospitalisations.
Additionally numerous studies have demonstrated a significant reduction
in suicide rates and aggressive behaviour among those taking clozapine.(7) Furthermore clozapine
has also been shown to be cost-effective in the treatment of refractory
schizophrenia.(5)
However
the benefits of clozapine therapy come at a high cost due to the drugs
high side effect burden.(8) Some of the more significant side effects
include weight gain, hypotension, tachycardia, agranulocytosis, myocarditis,
cardiomyopathy and sedation.(9) Although clozapine has a high side
effect burden; for patients suffering from treatment-resistant schizophrenia
clozapine is their last hope to manage their illness and live a ‘normal’
life.
It
is apparent that even with the adverse side effects clozapine treatment
can cause, clozapine therapy can have a significantly beneficial impact
on the lives of people with refractory schizophrenia. However there
is disparity in the reported prescription rates between studies; as
numerous studies have reported that clozapine treatment is underutilised.(10) Whereas others have reported that clozapine is well utilised
and the rates of prescription lie within the realm of the estimated prevalence
rates of refractory schizophrenia.(11)
Therefore
this paper investigates the prescription of clozapine in a region of
New South Wales (NSW), Australia between 2005 and 2010. In order
to ascertain whether clozapine therapy is being prescribed at a rate
that reflects the predicted prevalence of refractory schizophrenia in
the region. As it is only through reports detailing the ‘real world’
usage of anti-psychotics in clinical practice that future research can
be shaped (12), as well as highlighting issues of importance to clinicians.
This study is a retrospective review of the prescribing practices of
clozapine for the treatment of schizophrenia in a region of NSW, Australia
for the time period between 2005 and 2010. The archival data on the
rates of the prescription of clozapine are compared to the estimated
prevalence rates of refractory schizophrenia in the area.
This
study is based on data from region of NSW, Australia that covers approximately
6631 square kilometres and 13 different local Government areas. The
most recent census in 2006 reported the population in the region to
be 1.1 million. This is a total of 20% of the population of the state
of NSW. The socio-economic status of the area is comparatively less
disadvantaged than the rest of NSW. However there is significant variation
between the 13 local Government areas on this indicator.
Estimated Prevalence Rates of Schizophrenia
& Refractory Schizophrenia
It
is well known that schizophrenia has a global prevalence rate of 1%
(1), therefore based upon the region’s population of 1.1 million it
would be expected that 11’000 individuals in the region are suffering
from schizophrenia. Furthermore it is also apparent from previous work
that of those individuals afflicted with schizophrenia approximately
30% will have refractory or treatment resistant schizophrenia (2; 3).
Therefore from the above prevalence rate, a total 3’300 individual’s
with treatment-resistant schizophrenia are estimated to reside in the
area.
Clozapine Prescription in the Region
Between
the period of 2005 and 2010 a total of 277 individuals within the region
were prescribed clozapine. This is a mere 8.4% of the individuals estimated
to be suffering from treatment-resistant schizophrenia in the region.
Furthermore 141 of these individuals ceased clozapine treatment during
this time with only 136 patients continuing treatment to the present
time. Therefore only a total of 4.1% of those estimated to be suffering
from refractory schizophrenia are currently receiving clozapine treatment
in the area. This implies that the vast majority 95.9% or 3’164 individuals
estimated to be suffering from treatment-resistant schizophrenia in
the region are not receiving appropriate or the superior evidenced based
treatment for their condition.
It
is evident from the above study that the prescription of clozapine in
this region of NSW, Australia for the treatment of refractory schizophrenia
is immensely under-prescribed based upon the estimated prevalence rates
of treatment-resistant schizophrenia in the area. As out of the 3’300
individuals estimated to be suffering from treatment-resistant schizophrenia
in the area only 8.4% or 277 patients had been prescribed clozapine.
Furthermore only 4.1% or 136 patients had continued clozapine treatment
in the reported time period.
These
findings are in accordance with findings in the United States (U.S.)
where clozapine prescriptions only accounted for 5% of all anti-psychotics
prescribed.(6,13) Whereas Conley et al (13) study reported that clozapine
was used significantly more often in Australia in comparison to Maryland
in the U.S. However the study assessed clozapine use in a different
state of Australia; thus displaying the disparity in prescribing patterns
even in the same country. Similarly Fayek (14) reported that the rates
of prescribing clozapine were significantly different throughout the
United Kingdom. However other studies have reported that clozapine is
well utilised.(11,15,16) Therefore it is evident that there are inconsistencies
both in the practice of prescribing clozapine as well as the reports
of prescribing patterns in the literature.
The
under utilisation and disparity in the prescribing practices pertaining
to clozapine; an evidenced based treatment for refractory schizophrenia
not only results in significant costs to patients, their families, and
society, it leads to significant costs for the health system. Wheeler
et al (5) reports that the medical costs that result from patients
with refractory schizophrenia are high and account for the majority
of the overall cost of treating schizophrenia due to hospitalisations.
Furthermore Drew et al (17) found that long term use of clozapine (3-5
years) accounted for a $12 000 reduction in costs per patient per annum
in Australia.
It
is thought that the low prescription rates of clozapine in comparison
to the estimated prevalence rates may be related to the knowledge and
attitudes of prescribing clinicians. Nielsen et al (10) conducted a
study in Denmark and found that many psychiatrists were reluctant to
prescribe clozapine and had limited knowledge on the use of clozapine.
Furthermore the low prescription rates could pertain to the actual or
perceived logistical support for the necessary monitoring of patients
on clozapine.
Future
research needs to systematically address this issue by assessing the
beliefs, knowledge and attitudes of prescribing clinicians towards clozapine.
Such an endeavour would allow for the delineation of the reasons behind
the low prescription rates of clozapine. This would facilitate the development
of solutions to deal with the prevailing issues. Therefore bettering
the prognosis for those patients suffering from refractory schizophrenia,
helping their families and society; as well as lowering the health related
costs of caring for these individuals.
- Capuano B, Crosby IT, Lloyd EJ. Schizophrenia: Genesis, receptorology, and current therapeutics.
Current Medicinal Chemistry. 2002;9:521-548.
- Conley RR, Buchanan RW. Evaluation of treatment-resistant
schizophrenia. Schizophrenia Bulletin. 1997;23(4):663-674.
- Semiz UB, cetin M, Basoglu C, Ebrinc S, Uzun O, Herken
H, Balibey H, Algul A, Ates A. Clinical predictors of therapeutic
response to clozapine in a sample of Turkish patients with treatment-resistant
schizophrenia. Progress in Neuro-psychopharmacology & Biological Psychiatry. 2007;31:1330-1336.
- Angermyer MC, Loffler W, Muller
P, Schulze B, Priebe
S. Patients’ and relatives’ assessment of clozapine treatment. Psychological
Medicine. 2001;31:509-517.
- Wheeler A, Humberstone V, Robinson G. Outcomes for schizophrenia
patients with clozapine treatment: how good does it get? Journal of Psychopharmacology. 2009;23(8):957-965.
- Kelly DL, Kreyenbuhl J, Buchanan RW, Malhotra AK.
Why not clozapine? Clinical Schizophrenia. 2007;1:92-95.
- Henneen J, Baldessarini RJ. Suicidal risk during treatment
with clozapine: a meta-analysis. Schizophrenia Research 2005;73:139-145.
- Young CR, Bowers MB, Mazure CM. Management of the
adverse effects of clozapine. Schizophrenia Bulletin 1998;24(3): 381-390.
- Reznik I, Volchek L, Mester
R, Kotler M, Sarova-Pinhas I, Spivak B, Weizman A. Myotoxicity and neurotoxicity during clozapine
treatment. Clinical Neuropharmacology 2000;23(5):276-280.
- Nielsen J, Dahm M, Lublin H, Taylor D. Psychiatrists attitude
towards and knowledge of schizophrenia treatment. Journal of Psychopharmacology. 2010;24(7):965-971.
- Wheeler A, Humberstone V, Robinson G. Trends in anti-psychotic
prescribing in schizophrenia in Auckland. Australasian Journal of Psychiatry 2006;14(2):169-174.
- Marder SR. Can clinical practice guide a research agenda?
Schizophrenia
Bulletin. 2002;28(1):127-129.
- Conley RR, Kelly DL, Lambert TJ, Love RC. Comparison
of clozapine use in Maryland and in Victoria Australia. Psychiatric Services. 2005;56(3):320-323.
- Fayek M, Flowers C, Signorelli D, Simpson G. Psychopharmacology: underuse of evidence-based treatments in psychiatry.
Psychiatric Services. 2003;54(11):1453-1456.
- Mond J, Morice R, Owen C, Korten A. Use of antipsychotic
medications in Australia between July 1995 and December 2001. Australian and New Zealand Journal of Psychiatry. 2002;37:55-61.
- Weinbrenner S, Assion HJ, Stargardt
T, Busse R, Juckel
G, Gericke CA. Drug prescription patterns in schizophrenia
outpatients: analysis of data from a German health insurance fund. Pharmacopsychiatry
2008;41:1-6.
- Drew LRH, Griffiths KM, Hodgson DM. A five year follow-up
study of the use of clozapine in community practice. Australian and New Zealand Journal of Psychiatry 2002;36:780-786.
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