Clozapine Prescription Patterns in Australia Over the Last 10 Years

Clozapine is a clinically effective and well accepted therapy for patients with treatment-resistant schizophrenia. Both NICE guidelines and RANZCP guidelines recommend a trial of clozapine therapy if more conventional antipsychotic therapy is ineffective in the management of symptoms [1,2]. Our previous study was based on analysing the current use of clozapine in Australia (2009) and any interstate variations that were present [3]. The aim of this correspondence is to examine how the rates of clozapine use in Australia have changed over the last 10 years (2000–2009) and consider the possible reasons behind any variations.

Through personal communication and access to the Hospira database we were able to ascertain the amount of clozapine that had been imported into Australia from 2000–2009 [Hospira, personal communication]. This allowed us to calculate the amount of clozapine being imported into Australia, per 1000 people over the age of 16 (Australian Bureau of Statistics) [4], per year (Table 1).

Table 1.

Amount of clozapine imported (mg/1000 population over age 16)

2000	134 mg
2001	142 mg
2002	163 mg
2003	177 mg
2004	190 mg
2005	206 mg
2006	217 mg
2007	228 mg
2008	235 mg
2009	238 mg

As can be seen below, clozapine importation has significantly increased over the last 10 years from 134 mg/1000 population in 2000 to 238 mg/1000 population in 2009. Since this data is comparing the amount of clozapine imported to the number of people in Australia (over age 16), an increase in the numbers below represents a disproportionate increase in clozapine importation as compared to the population numbers, which in turn suggests that during these years there has been a significant change in the prescription patterns of clozapine.

Our data also suggests that the average dose of clozapine has remained relatively constant (at 400 mg) over these 10 years [Hospira, personal communication], meaning that the most likely reason behind this significant increase in clozapine importation is an increase in the number of patients on clozapine therapy. Some clues as to the underlying reasons behind this increase in prescription of clozapine can be gathered through analysing the yearly change in importation of clozapine (Table 2).

Table 2.

Yearly change in clozapine importation (mg/1000 population over age 16)

2000–2001	7 mg
2001–2002	21 mg
2002–2003	14 mg
2003–2004	13 mg
2004–2005	16 mg
2005–2006	11 mg
2006–2007	11 mg
2007–2008	8 mg
2008–2009	3 mg

As can be seen from the data below, the rate of increase in clozapine importation appears to be the highest between 2001 and 2007 with an average increase of 14 mg/year/1000 population. During this period there are also two noticeable peaks, one between 2001 and 2002 with an increase of 21 mg/year/1000 population, and the second between 2004 and 2005 with an increase of 16 mg/year/1000 population. Following this period, the rate of increase in clozapine importation is seen to drop off, with 7 mg/year/1000 population increase between 2007 and 2008 and 3 mg/year/ 1000 population increase between 2008 and 2009. It is interesting to note that the two mentioned peaks coincide very closely with the release of NICE guidelines in 2002 and RANZCP guidelines in 2005, thus possibly representing the power of guidelines in affecting clinical practice. It is also important to note that the plateau in the rate of importation experienced between 2007 and 2009 is also not unexpected, given that clozapine is reaching its utilization potential, with approximately 58% of Treatment Resistant Schizophrenia (TRS) patients being on clozapine in Australia in 2009 [3].

Clozapine use in Australia currently requires very stringent, regular monitoring, and there has been discussion in this journal as to whether there should be liberalization of these controls [5] as there has been in countries such as the Netherlands [6]. Nevertheless, clozapine prescription has increased by 78% over the last 10 years. This increase, despite the presence of newer antipsychotic medications such as risperidone, olanzapine, quetiapine, amisulpride, ziprasidone and aripiprazole is not only an indicator of prescription guidelines being followed closely but is also an indicator of clozapine's significant biological effects and success in patients with TRS.