Sage Journals: Discover world-class research

Abstract

Objective: Internationally there has been an increase in the prescriptions of stimulant medication. The aim of this study was to examine longitudinal national trends of stimulant dispensing in Australia between 2002 and 2009.

Method: Government databases were retrospectively reviewed for all dispensed stimulant prescriptions between 2002 and 2009. Prescriptions were converted to defined daily dose (DDD)/1000 population/day using census data. Utilization of dexamphetamine and methylphenidate were analysed by source (subsidized or non-subsidized), prescriber (general practitioner, psychiatrist or other specialists), gender and age of patient.

Results: Between 2002 and 2009, dispensing of stimulants in Australia increased 87% from 2.93 to 5.47 DDD/1000 population/day. Dexamphetamine remained the most commonly dispensed stimulant, with rates of dispensing falling 13% from 2.02 to 1.75 DDD/1000 population/day. Dispensed prescriptions of methylphenidate increased 300% from 0.45 in 2002 to 1.81 DDD/1000 population/day in 2009, attributable to the availability of long-acting preparations. Dispensing of stimulants to males was four-fold greater than to females. There was substantial dispensing of dexamphetamine to those older than 25 years.

Conclusions: Stimulant dispensing in Australia increased between 2002 and 2009 as a result of increased dispensing of long-acting preparations of methylphenidate. Further research is required to determine if the increase in stimulant dispensing in Australia is clinically appropriate.

Keywords

dexamphetamine dispensing methylphenidate pharmacoepidemiology stimulants

Stimulants have been used in medicine since 1935 for treatment of a variety of conditions including attention deficit hyperactivity disorder (ADHD), narcolepsy, obesity and depression [1]. Currently in Australia, short acting preparations of methylphenidate and dexamphetamine have Therapeutic Goods Administration (TGA) indications for ADHD and narcolepsy. Long-acting preparations of methylphenidate are only indicated for ADHD [2]. Given the low prevalence of narcolepsy, estimated to be 25–50 per 100,000 [3], the majority of stimulant prescribing in Australia is thought to be for attention deficit hyperactivity disorder.

In 1998, the Australian child and youth national survey of mental health and well-being estimated the 12-month prevalence of ADHD in children aged 6 to 17 years was 11.2% with a higher prevalence in men (15.4%) than women (6.8%) [4]. In some individuals there is a continuation of symptoms into adulthood [5] with the full disorder persisting in 15% of subjects at age 25 years. Between 40% and 60% of adult subjects met criteria for partial remission of ADHD [6].

Psychosocial interventions are the first line treatments for ADHD. Pharmacotherapy should be reserved for those individuals with more severe symptoms or impairment, or for those individuals with moderate impairment who have not responded to psychosocial interventions. Stimulants (methylphenidate and dexamphetamine) have been shown to be a cost effective intervention for ADHD [7] and are recommended as the first line pharmacotherapy for ADHD [8].

International trends in prescribing of stimulants have been reported. Studies conducted in Canada, France, Netherlands, California, Israel and Australia have all shown increases in stimulant prescribing in recent years. Differences in the duration of the study period, the baseline rates of stimulant prescribing and age of patients receiving stimulant medication (children only compared to children and youth) prevents direct comparison of the studies [9–14].

Studies have reported trends of stimulant use in Australian states with an increase in the use of stimulants in children in Western Australia and New South Wales between 1984 and 2004 [15,16] and in adults in New South Wales between 1990 and 2002 [17]. There were regional variations in Western Australia with stimulant prescribing rates in urban areas 2.3 to 5.3 times greater than remote areas [18]. In South Australia there has been no consistent trend of change in stimulant prescribing with rates of prescriptions varying between 1990 and 2006 [19].

We examined the national rates of dispensed prescriptions of stimulant medication for children, youth and adults in the Australian population between 2002 and 2009 and report the trends in dispensed stimulant prescriptions over this time by gender and age.

Methods

Data and data analysis

The data on the number of prescriptions dispensed for stimulants were obtained from the Drug Utilisation Sub-Committee (DUSC) of the Australian Department of Health and Ageing, The data were drawn from two sources. The first was the Medicare Australia records of prescriptions submitted for payment of a subsidy under the Pharmaceutical Benefits and Repatriation Pharmaceutical Benefits Schemes (PBS/RPBS). The second was an ongoing survey of a representative sample of community pharmacies from the Pharmacy Guild of Australia, which provides an estimate of the non-subsidized (private and under general co-payment) use of prescription medicines in the Australian community [20]. The majority of prescriptions (92%) dispensed in the Australian community (including residential care) were subsidized through the PBS. Although stimulants were publicly subsidized for those who met the Authority restrictions, it was also possible to obtain a private prescription at a higher cost to the patient.

Anonymized data on subsidized scripts included details of the drug product dispensed and information on the patient's gender and age. The use of prescription medicines dispensed to inpatients in public hospitals was not available for this report. In Australia, discharged patients from hospital are typically provided with only a short supply of medications, typically a maximum of one month's supply. Further prescriptions are provided by medical practitioners in the community. Data was also available on the average number of stimulants written by three different classes of prescribers: general practitioners (GPs); psychiatrists; and ‘other specialists’, which included paediatricians. Data differentiating other specialties and sub-specialisms were unavailable.

The quantity of each drug dispensed was standardized using the defined daily dose (DDD) per 1000 population per day (DDD/1000 population/day). The DDD, established by the WHO Collaborating Centre for Drug Statistics Methodology, corresponds to an estimated average daily dose used for a medication's principal indication [21]. Utilization was calculated for drugs with an anatomical therapeutic chemical code starting with N06BA, indicating psychostimulants. The drugs (with the defined daily dose in brackets) included: dexamphetamine (15 mg), methylphenidate (30 mg) and modafinil (300 mg). Age-standardized drug utilization rates for women and men were calculated for the period June 2002 to June 2009 (with appropriate half-year adjustment) using census mid-year population data [22]. For example, the utilization of 10 DDD/1000/day of dexamphetamine would correspond to about 1% of the population taking a standard 15 mg of dexamphetamine each day. Information on the gender and age of persons receiving a prescription were not available before 2002 as date of birth was not verified in prescription data prior to this.

All calculations were completed using Microsoft Office Excel 2003. The dataset incorporates all prescriptions in the time period studied. The large number of prescriptions would render all differences as statistically significant, regardless of clinical relevance [23].

Results

Overall use of individual stimulants

Total dispensing of stimulants increased 87% from 2.93 to 5.47 DDD/1000 population/day between 2002 and 2009 (Figure 1), representing an average increase of 11% per year. Although dexamphetamine prescriptions fell 13% from 2.02 to 1.75 DDD/1000 population/day and was dispensed almost exclusively through the PBS, total methylphenidate dispensing between 2002 and 2009 increased by 300%, from 0.45 to 1.81 DDD/1000 population/day in 2009. Most of the increase in methylphenidate can be attributed to the increase in dispensing of long-acting preparations. Methylphenidate 10 mg use increased after it became subsidized on the PBS in August 2005. There was immediate uptake of the extended release formulation of methylphenidate after it was introduced in April 2007, in addition to the existing use of the short-acting forms.

Figure 1.

Drug utilization (DDD/1000 population/day) of dexamphetamine, methylphenidate (MP; short-acting, long acting and total) and combined total for each month between July 2002 and June 2009.

Stimulant use by class of prescriber

Figure 2 shows stimulant dispensing by category of prescriber averaged over twelve month periods in 2003, 2006 and a 6-month period in 2009. Dispensed prescriptions written by general practitioners (GPs) for dexamphetamine remained stable over time (Figure 2). From January 2009 to June 2009, GP prescriptions for dexamphetamine were dispensed on average 1.7 times more than methylphenidate (0.25 versus 0.15 DDD/day) and prescriptions for dexamphetamine written by psychiatrists were dispensed 3.9 times more than methylphenidate in the same period (0.52 versus 0.13 DDD/day). Prescriptions for methylphenidate written by ‘other specialists’ (including paediatricians) were dispensed 4.5 times more than dexamphetamine (1.18 versus 0.26 DDD/day). There was a 61.7% decrease in the average number of dexamphetamine prescriptions dispensed between 2002–2004 (0.78 DDD/1000 population/day) and 2007–2009 (0.3 DDD/1000 population/day) for ‘other specialists’ compared to a 17.1% reduction in dexamphetamine prescriptions by psychiatrists (0.63 to 0.52 DDD/1000 population/day). There was an almost three-fold increase in dispensing of methylphenidate prescriptions written by ‘other specialists’ between 2006 and 2009 from 0.32 to 1.21 DDD/1000 population/day.

Figure 2.

Drug utilization (DDD/day, averaged for each month within a year) for dexamphetamine and methylphenidate by prescriber category (GP, psychiatrist or other specialist, including paediatricians) for 2003, 2006 and 2009.

Stimulant use by gender and age

In 2007, age- and population-adjusted stimulant dispensing was higher in men than women (Figure 3) consistent with the higher prevalence of ADHD in men [2]. Until 2007 the data was received in 5-year age groups (which show more detail) but in 2008 and 2009 the data was provided only in 10-year age groups (data not shown). In 2007 (averaged over the first 6 months), dexamphetamine and methylphenidate were most commonly dispensed to patients aged 10–14 years: dexamphetamine dispensing was 1.3 DDD/1000 population/day in girls and 5.76 DDD/1000 population/day in boys, a 4.4-fold difference. The corresponding dispensing for methylphenidate was 2.07 DDD/1000 population/day in girls and 10.36 DDD/1000 population/day in boys, a 5-fold difference. The dispensing in boys aged 10–14 years corresponds to about 1.04% of boys aged 10–14 years receiving a standard dose of methylphenidate (30 mg) each day. Methylphenidate dispensing decreased for those aged 15 years or more and there was little dispensing of methylphenidate for those aged 25 years or over. There was, however, considerable dispensing of dexamphetamine to those aged over 25 years, with a gradual decline across the lifespan. The continued dispensing of dexamphetamine was observed in both women and men, with a greater magnitude in men. There was residual dispensing of dexamphetamine into older ages: 0.05 and 0.1 DDD/1000 population/day in women and men aged 80–84 years, respectively.

Figure 3.

Subsidized dexamphetamine and methylphenidate utilization (DDD/1000 population/day) by gender (women on the left, men on the right) by five-year age groups (0–64 years) for 2007 (average of first 6 months).

Discussion

There was an 87% increase in stimulant dispensing in Australia between 2002 and 2009. Dexamphetamine remained the most commonly dispensed stimulant, with prescriptions falling 13% between 2002 and 2009. The increase in stimulant dispensing was attributable to a 300% increase of dispensed methylphenidate following PBS subsidization of the short-acting preparations from 2005 and longer acting preparations from 2007. Although the most likely explanation for the increase in methylphenidate dispensing was government subsidy, increased prescribing of stimulants for ADHD has also been reported in North America and Europe [9–13]. We conjecture that this may be due to a number of factors including studies showing the effectiveness of stimulants for ADHD treatment [24], increased public awareness of ADHD, societal changes (for example children living in smaller housing, greater expectations of students to remain at school) and the influence of marketing by pharmaceutical companies [25].

Dispensing of stimulant prescriptions for both men and women peaked at 10–14 years of age. We hypothesize that this coincides with increasing cognitive demands in the school environment and increasing expectations from parents, teachers and perhaps the students themselves.

The use of stimulants was approximately five times greater in men than women, although the Australian prevalence of ADHD is 2.45 times greater in men than women [4]. Thus the amount of stimulants dispensed to men compared to women is disproportionately greater compared to the relative sex differences in the prevalence of the disorder. This may be explained by a gender difference in symptom profiles with men more likely to have comorbid disruptive behavioural disorders compared to women [26]. Additionally, the doses prescribed to men may have been on average higher than those prescribed to women resulting in the increased drug utilization in men relative to women.

The rising trend of stimulant dispensing over the study period will inevitably draw public scrutiny. In 2007, approximately 1% of men and 0.5% of women aged 10 to 14 in Australia were dispensed stimulant medication. This is lower than the reported Australian or international prevalence of ADHD [4,27]. Medical practitioners need to provide patients and carers with both pharmacological and non-pharmacological options for the management of ADHD and collaboratively determine the most appropriate management for each individual. Future epidemiological surveys should examine whether the use of stimulants is restricted to a minority of patients with ADHD symptoms, as was evident in the national survey conducted in 1998 [28].

There are several limitations in this study. Beyond gender and age, we were unable to determine other characteristics of stimulant medication users. Further research is needed to explore which patients are receiving stimulants. Dispensed prescriptions may not reflect actual medication consumption. Stimulants are recognized as potential drugs of abuse and the risk of diversion of stimulants remains a potential problem [29].

We were unable to determine what proportion of stimulant dispensing was for narcolepsy [3] or the short-term treatment of depression [30], particularly for older persons [31]. The Drug Utilisation Sub-Committee (DUSC) and Pharmacy Guild data do not allow for gender or age stratification in private or under general co-payment prescription data. Thus there are limitations on data analysis of non-subsidized scripts. The use of prescription medicines dispensed to inpatients in public hospitals is not captured by this study but the missed contribution is likely to be small compared with overall prescribing rates.

The defined daily doses are standardized as the maintenance dose in adults. Hence, the lower DDD in younger children compared to the 10–14 year olds may reflect a lower dosage rather than a lower number of patients prescribed stimulants. Similarly, doses prescribed to adults may be higher than those prescribed to 10–14 year olds. Therefore, the data presented here, especially for young children, are likely to be conservative. No further information was available on the ‘other specialists’ category of prescribers. Although we believe this will consist predominantly of paediatricians, we have no way of verifying this. Previous research has shown interstate and intrastate variability in stimulant prescribing [14–19]. Unfortunately, data available from the Drug Utilisation Sub- Committee (DUSC) of the Australian Department of Health and Ageing did not allow interstate comparisons.

In spite of the above limitations, this is the most comprehensive report to date of Australian national trends of stimulant dispensing. A major strength of this study is that it represents the complete capture of all subsidized dispensing of stimulant medications by gender and age in the Australian community during the study period. This study may serve as a baseline against which to compare national use of stimulant medication. Given the availability of different formulations of methylphenidate, it will be of interest to examine how the availability of new agents such as atomoxetine [32] influences the prescribing behaviours of Australian medical practitioners for treatment of ADHD. It will also be of interest to examine whether this trend of increased stimulant dispensing continues.

Footnotes

Acknowledgements

We acknowledge the assistance of Hera Lutsenko in data analyses.

Declaration of interest: Drs Stathis, Varghese and Scott have been sponsored by Janssen-Cilag and Eli Lilly to attend educational meetings. The data were provided by the Drug Utilisation Sub-Committee, Pharmaceutical Benefits Branch, Australian Government Department of Health and Ageing. No ethical approval was required as we used only secondary de-identified data sources. This study was funded from existing salaries. The authors alone are responsible for the content and writing of the paper.

References

1. Greenhill

Pliszka

Dulcan

. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2002; 41S2:26–49.

2. e Business Services Australian Register of Therapeutic Goods. Information about prescription medicines in Australia. [Cited 9 November 2011]. Available from URL https://www.ebs.tga.gov.au/.

3. Longstreth

Jr Koepsell

Ton

Hendrickson

van Belle

. The epidemiology of narcolepsy. Sleep 2007; 30:13–26.

4. Sawyer

Arney

Baghurst

. The mental health of young people in Australia: key findings from the child and adolescent component of the National Survey of Mental Health and Well-Being. Aust N Z J Psychiatry 2001; 35:806–814.

5. Polanczyk

Rohde

. Epidemiology of attention deficit/hyperactivity disorder across the lifespan. Curr Opin Psychiatry 2007; 20:386–392.

6. Faraone

Biederman

Mick

. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med 2006; 36:159–165.

7. Donnelly

Haby

Carter

Andrews

Vos

. Cost-effectiveness of dexamphetamine and methylphenidate for the treatment of childhood attention deficit hyperactivity disorder. Aust N Z J Psychiatry 2004; 38:592–601.

8. National Collaborating Centre for Mental Health. Attention deficit hyperactivity disorder. Diagnosis and management of ADHD in children, young people and adults. NICE clinical guideline 72. London: National Institute for Health and Clinical Excellence, 2008.

9. Knellwolf

Deligne

Chiarotti

. Prevalence and patterns of methylphenidate use in French children and adolescents. Eur J Clin Pharmacol 2008; 64:311–317.

10.

10. Schirm

Tobi

Zito

de Jong-van den Berg

. Psychotropic medication in children: a study from the Netherlands. Pediatrics 2001; 108:E25.

11.

11. Habel

Schaefer

Levine

Bhat

Elliott

. Treatment with stimulants among youths in a large California health plan. J Child Adolesc Psychopharmacol 2005; 15:62–67.

12.

12. Vinker

Vinker

Elhayany

. Prevalence of methylphenidate use among Israeli children: 1998–2004. Clin Drug Investig 2006; 26:161–167.

13.

13. Miller

Lalonde

McGrail

Armstrong

. Prescription of methylphenidate to children and youth, 1990–1996. Can Med Assoc J 2001; 165:1489–1494.

14.

14. Berbatis

Sunderland

Bulsara

. Licit psychostimulant consumption in Australia, 1984–2000: international and jurisdictional comparison. Med J Aust 2002; 177:539–543.

15.

15. Valentine

Zubrick

Sly

. National trends in the use of stimulant medication for attention deficit hyperactivity disorder. J Paediatr Child Health 1996; 32:223–227.

16.

16. Salmelainen

. Trends in the prescribing of stimulant medication for the treatment of attention deficit hyperactivity disorder in children and adolescents in New South Wales. NSW Public Health Bull Suppl 2002; 13:1–65.

17.

17. Salmelainen

. Trends in the prescribing of stimulant medication for the treatment of Attention Deficit Hyperactivity Disorder in adults in NSW. NSW Public Health Bull Suppl 2004; 15:1–55.

18.

18. Calver

Preen

Bulsara

Sanfilippo

. Stimulant prescribing for the treatment of ADHD in Western Australia: socioeconomic and remoteness differences. Med J Aust 2007; 186:124–127.

19.

19. Prosser

Reid

. Changes in use of psychostimulant medication for ADHD in South Australia (1990–2006). Aust N Z J Psychiatry 2009; 43:340–347.

20.

20. Australian Government Department of Health and Ageing. Australian statistics on medicines 2008. Canberra: Department of Health and Ageing, 2009.

21.

21. World Health Organization. World Health Organization Collaborating Centre for Drug Statistics Methodology. ATC index with DDDs, 2005. Oslo: WHO, 2005.

22.

22. Australian Bureau of Statistics. Population by age and sex, Australian states and territories, June 2002 to June 2009. (Cited 4 May 2010.) Available from URL http://www.abs.gov.au/AUSSTATS/abs@.nsf/MF/3201.0.

23.

23. Sterne

Davey Smith

. Sifting the evidence: what's wrong with significance tests? Br Med J 2001; 322:226–231.

24.

24. Van der Oord

Prins

Oosterlaan

Emmelkamp

. Efficacy of methylphenidate, psychosocial treatments and their combination in school-aged children with ADHD: a meta-analysis. Clin Psychol Rev 2008; 28:783–800.

25.

25. Tobin

de Almedia Neto

Wutzke

. Influences on the prescribing of new drugs. Aust Fam Physician 2008; 37:78–80.

26.

26. Levy

Hay

Bennett

McStephen

. Gender differences in ADHD subtype comorbidity. J Am Acad Child Adolesc Psychiatry 2005; 44:368–376.

27.

27. Polanczyk

de Lima

Horta

Biederman

Rohde

. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007; 164:942–948.

28.

28. Sawyer

Rey

Graetz

Clark

Baghurst

. Use of medication by young people with attention-deficit/hyperactivity disorder. Med J Aust 2002; 177:21–25.

29.

29. Wilens

Adler

Adams

. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008; 47:21–31.

30.

30. Candy

Jones

Williams

Tookman

King

. Psychostimulants for depression. Cochrane Database Syst Rev 2008; 2:CD006722.

31.

31. Wallace

Kofoed

West

. Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients. Am J Psychiatry 1995; 152:929–931.

32.

32. Adler

Spencer

Brown

. Once-daily atomoxetine for adult attention deficit/hyperactivity disorder: a 6-month, double-blind trial. J Clin Psychopharmacol 1999; 29:44–50.

Australian National Trends in Stimulant Dispensing: 2002–2009