Attention Deficit Hyperactivity Disorder (ADHD) in the United Kingdom: Regional And

1

Attention Deficit Hyperactivity Disorder (ADHD) in the United Kingdom: Regional and socioeconomic variations in incidence rates (2004-2013)

Adrian J Hire1, Darren M Ashcroft1, David A Springate2and Douglas T Steinke1

1Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom

2Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom

Corresponding Author: Adrian J Hire, Manchester Pharmacy School, Room 1.134 Stopford Building, Oxford Road, Manchester, M13 9PT. Email:

Author biographies

Adrian J Hire, MPharm, is a PhD student based within Manchester Pharmacy School at the University of Manchester.

Darren M Ashcroft, PhD, is professor of pharmacoepidemiology at the University of Manchester and director of the Centre for Pharmacoepidemiology and Drug Safety at Manchester Pharmacy School.

David A Springate, PhD, is a research fellow in the Institute of Population Health at Manchester University. He uses electronic health records to answer a broad range of questions in primary healthcare.

Douglas T Steinke, PhD, is a senior lecturer in pharmacoepidemiology at Manchester Pharmacy School, University of Manchester. His research interest is in medicines use in chronic diseases, health services and drug utilisation research.

Abstract

Objective: To describe the incidence and distribution of ADHD within the United Kingdom, and to examine whether there was any association between ADHD incidence and socioeconomic deprivation.

Method: The study used data from the Clinical Practice Research Datalink (CPRD). Patients diagnosed with ADHD before the age of 19 between January 1, 2004 and December 31, 2013 were stratified according to the region in which their general practice was based. Practice Index of Multiple Deprivation (IMD) score was used as a surrogate measure of patients’ deprivation status. Results: ADHD incidence was relatively stable between 2004 and 2013, but peaked in the last 2 years studied. Statistically significant (p .05) differences in incidence were observed between U.K. regions. In almost every year studied, incidence rates were highest among the most deprived patients and lowest among the least deprived patients.

Conclusion: In the United Kingdom, ADHD may be associated with socioeconomic deprivation.

Keywords

ADHD, incidence, variation, deprivation

Introduction

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by three core symptoms: hyperactivity, impulsivity and inattention (Bolea-Alamañac et al., 2014). In the United Kingdom (UK) general practitioners (GPs) play a key role in the diagnosis, management and treatment of the disorder. As gatekeepers to the UK healthcare system (Herrett et al., 2015; Murray et al., 2014), GPs will generally be the first port of call for individuals concerned that they or their child may have ADHD. After referring suspected cases to secondary care (such as paediatric or psychiatry services) for a confirmation of the diagnosis, GPs may prescribe medications and undertake monitoring measures as part of a shared care arrangement (National Institute for Health and Care Excellence, 2008a). Four medications are currently licensed in the United Kingdom for the treatment of ADHD (methylphenidate, dexamfetamine, lisdexamfetamine and atomoxetine)(Joint Formulary Committee, 2015), though pharmacological intervention may not be required in all cases (McCarthy et al., 2012).

McCarthy et al. (2012) and Holden et al. (2013) both detectedincreases in the incidence and prevalence of ADHD in the UK during the first decade of the 21st century. However, there is some evidence to suggest that the burden of the disorderis unevenly distributed. Rowlingson et al. (2013)observed that primary care spending on methylphenidate varied significantly across England. In addition, a UK cohort study by Russell et al. (2014) found that ADHD was particularly prevalent amongst children living in circumstances of social and economic disadvantage.

The findings of Rowlingson et al. (2013) were based on national prescribing data from a single month in 2011. Similarlythe link between parentally-reported ADHD and socioeconomic deprivation was based on a sample containing a relatively small number (n=187) of affected children (Russell et al., 2014). The aim of this study was to establish if the regional prescribing variations observed in the UK reflected regional variations in ADHD incidence, and to determine if ADHD incidence showed any association with socioeconomic deprivation on a national scale. The study also sought to update the findings ofearlier epidemiological studies, describing ADHD incidence rates amongst children and adolescents in the UK between the years 2004 and 2013.

Method

Data source

A retrospective cohort study was performed using primary care consultation data from the Clinical Practice Research Datalink (CPRD). This data consists of information routinely recorded by general practitioners during their consultations with individual patients, including diagnoses made and medications prescribed. CPRD has been collating anonymised patient-level data from UK general practices since its inception (as the ‘General Practice Research Database’) in 1987(Mansell, 2013). General practices that contribute data to CPRD are required to meet certain data quality requirements before they are declared ‘up to standard’ for research purposes (Bhaskaran, Forbes, Douglas, Leon, & Smeeth, 2013).Only data from these ‘up to standard’ practices was included in the study. The number of general practices sharing data with the CPRD has expanded steadily over time. At the time the study was conductedCPRDheld longitudinal, research-quality data for 684 UK general practices(Clinical Practice Research Datalink, 2014). This equates to around 9% of the UK’s general practices(Mansell, 2013) and records for approximately 13.5 million individuals(Clinical Practice Research Datalink, 2014), a large sample that is broadly representative of the UK population as a whole(Bushe, Wilson, Televantou, Belger, & Watson, 2015; Herrett et al., 2015; Holden et al., 2013; Thomas, Mitchell, & Batstra, 2014; West, Fleming, Tata, Card, & Crooks, 2014).

Study population and study period

The study population comprised patients diagnosed with ADHD before the age of 19, between 1/1/2004 and 31/12/2013. Data stored within CPRD is coded; terminology relating to patients’ clinical management is encoded using a standardised set of codes termed ‘Read codes’ to promote consistency and uniformity(Chisholm, 1990). Individuals with a diagnosis of ADHD were identified by the presence of Read codes relating to the disorder in their CPRD record. To be eligible for inclusion as an incident case of ADHD the earliest occurrence of a relevant code had to occur within the study window, and following at least 365 days continuous registration with their general practice. A list of Read codes denoting a diagnosis of ADHD and a further list of Read codes denoting drugs used in its treatment were compiled (both lists available at clinicalcodes.org, an online repository for clinical codes used in database research (Springate et al., 2014)). The drugs selected encompassed all agents currently licensed for the treatment of ADHD in the UK - methylphenidate, dexamfetamine, lisdexamfetamine and atomoxetine. All four drugs are licensed for use in patients between the ages of six and eighteen years of age; atomoxetine is also approved for use in adults (Joint Formulary Committee, 2015). With the exception of dexamfetamine (which is also licensed for the treatment of narcolepsy), the drugs of interest examined by this study are solely licensed for the treatment of ADHD(Joint Formulary Committee, 2015).

Assessment of geographical location

Every practice contributing data to CPRD has a unique identifying number. Associated with this number is information about that practice’s geographical location within the UK. By looking at the practice identifier associated with a particular patient, their location within the UK can be discerned. CPRD subdivides the UK (a nation itself comprised of four ‘nations’ – England, Scotland, Wales and Northern Ireland)into thirteen geographical regions.Scotland, Wales and Northern Ireland comprise three of these regions; the remainder areregions situated within England (North West, North East, Yorkshire and the Humber, East Midlands, West Midlands, East of England, South West, South Central, London and the South East Coast)(West et al., 2014).

Assessment of deprivation: ‘Practice-level’ deprivation score

England and Wales are divided up into approximately 35,000 defined geographical areas known as Lower Layer Super Output Areas (LSOA) (Office of National Statistics, 2015). Generated for the purposes of statistical research, these areas each contain populations of between 1000 and 3000 people(Office of National Statistics, 2015). Similar geographic divisions are applied to Northern Ireland and Scotland, which is divided into smaller areas termed datazones (DZ)(UK Data Service, 2014). Measurements relating to seven key indicators of socioeconomic deprivation are routinely compiled for each LSOA/DZ. These indicators examine household income, employment, health and disability, education and training, barriers to housing and services, crime and the living environment(UK Data Service, 2014). An amalgamation of this information is used to calculate an Index of Multiple Deprivation (IMD) score for each LSOA/DZ, allowing each to be ranked in order of relative deprivation.

Every general practice contributing data to CPRD has an Index of Multiple Deprivation score based on the LSOA/DZ in which it is situated. These scores are available to CPRD researchers, rounded to the nearest quintile. For the purposes of this study, ‘practice-level’ IMD scores were used as a surrogate measure of patients’ deprivation status. This measure was deemed appropriate as patients would be expected to reside in the locality of their general practice, within a geographically-defined catchment area(NHS Choices, 2014).

Assessment of deprivation:‘Patient-level’ deprivation score

For around 70% of English practices (covering just over 50% of all patients in CPRD) IMD scores can be provided for individual patients based on the LSOA in which their home address is situated(Thomas, 2014). This direct measure of deprivation status was requested for the subset of ADHD patients for whom it was available. By comparing these individuals’ practice-level IMD score to their patient-level IMD score, it could be established if practice-level deprivation scores provided an accurate reflection of patient-level deprivation scores.

Data Analysis

Incidence calculation: The earliest occurrence of an ADHD-related Read code in each patient’s records was identified, and the calendar year in which this occurred was noted. The patient was then counted as a newly-diagnosed incident case for that calendar year. The incidence denominator for each year comprised of person-time contributed by individuals who were considered ‘at risk’ of developing ADHD in that year.

Incidence rates were expressed as cases per 10,000 person years at risk (PYAR)and presented with 95% confidence intervals (CI).Annual incidence rates were calculated and stratified according to patient gender, nation (England/Scotland/Wales/Northern Ireland)and practice-level deprivation (IMD) quintile. An overall incidence rate was calculated for the study period as a whole; this was stratified according to gender, nation, CPRD region (in the case of English patients), age group and deprivation quintile.MultivariablePoisson modelling was used to determine incidence rate ratios (IRR) and accompanying 95% confidence intervals and p-values, adjusted for gender, nation, age groupand deprivation quintile. A regression was similarly conducted using only English patients; this was adjusted for gender, age group, CPRDregion and deprivation quintile.Statistical significance was set at p≤0.05, and all statistical analyses were performed using STATA version 13(Stata Statistical Software, College Station, TX, USA).

Results

Overall and annual incidence rates (UK)

Over the 10 year study period 10,284 new diagnoses of ADHD were recorded in under 19s in CPRD. The overall ADHD incidence rate for the study period was 11.67 cases per 10,000 person-years at risk (95%CI 11.45 – 11.90). Incidence rates were at their lowest in 2008 [11.04 cases per 10,000 PYAR (95% CI 10.38 – 11.75)] and highest in 2012 [12.56 cases per 10,000 PYAR (95% CI 11.84 – 13.33)], as shown in Figure 1.

Incidence by gender and age group

After adjustment for nation,deprivation quintile and age group, a large and statistically significant difference (p≤0.001) in incidence rates was observed between males and females. Between 2004 and 2013 the overall incidence of ADHD amongst the male population at risk was 18.63 cases per 10,000 PYAR (95% CI 18.24 – 19.03). The overall incidence rate in females was much lower [4.37 cases per 10,000 PYAR (95% CI 4.18 – 4.57)]. As shown in Figure 1, female incidence rates were relatively static from 2004 – 2010 but were notably higher in the last three years of the study period[peaking at 5.45 cases per 10,000 PYAR (95% CI 4.80 – 6.21) in 2012].

Figure 2 shows the incidence of ADHD in males and females according to age group. In both males and females, ADHD was most commonly diagnosed at age seven (1,057 new diagnoses in males, 238 new diagnoses in females). Thirty five percent of all ADHD patients identified (n=3,606) were diagnosed between the ages of seven and nine.

Incidence by nation (England, Scotland, Wales and Northern Ireland)

As shown in Table 1, Northern Ireland’s overall incidence rate was the highest of the four UK nations [with 13.32 cases per 10,000 PYAR (95% CI 12.11 – 14.66)]. This was significantly higherthan that of Scotland (p≤0.001), England (p≤0.001) and Wales (p=0.015). Wales had the second highest incidence rate across the study period, significantly higher than that of England (p=0.012) and Scotland (p=0.010). Scotland’s overall incidence rate was the lowest of the four nations, though the difference between Scottish and English rates was not statistically significant (p=0.359).

In England, annual fluctuations in incidence rates broadly corresponded to those of the UK as a whole. Incidence rates were at their lowest in 2008 and highest in 2012 [peaking at 12.73 cases per 10,000 PYAR (95% CI 11.90 – 13.62)]. However, adecrease in incidence rates between 2007 [11.87 cases per 10,000 PYAR (95% CI 11.10 – 12.70)] and 2008 [10.27 cases per 10,000 PYAR (95% CI 9.55 – 11.05)] was observed in England but not observed in the UK data as a whole.

In Scotland, ADHD incidence was lowest in 2005 [7.60 cases per 10,000 PYAR (95% CI 6.00 – 9.62)] and highest in 2013 [14.80 cases per 10,000 PYAR (95% CI 12.52 – 17.48)].In contrast to England, 2008 saw a relatively high incidence of newly-diagnosed ADHD in Scotland and peak annual incidence in Northern Ireland [15.46 cases per 10,000 PYAR (95% CI 11.62 – 20.58)]. In Wales, peak ADHD incidence was observed in 2007 [15.63cases per 10,000 PYAR (95% CI 12.98 – 18.83)].

Incidence by CPRD region (England)

Within each English region annual incidence rates fluctuated between the years 2004 and 2013 without any consistent pattern. However, the South East Coast region had both the highest number of ADHD diagnoses during the study period (n=1,461, 18.3% of the England’s total cases) and the highest overall incidence rate of ADHD in under 19s (see Table 2). This was significantly higher (p≤0.001) than that of the Yorkshire and the Humber region, which had the lowest incidence rate of England’sten CPRD regions.

Incidence by deprivation (IMD) quintile

When stratified according to deprivation quintile, the UK’s diagnostic data suggested a significant link between deprivation and ADHD incidence. In almost every year studied, incidence rates were highest in the most deprived patients and lowest in the least deprived patients (see Figure 3).Underlying this UK trend was England’s diagnostic data. Patients belonging to practices in the most deprived areas of England (IMD quintile 5) had the highest incidence of ADHD overall [13.84 cases per 10,000 PYAR (95% CI 13.23 – 14.47)]. This was significantly higher (p≤0.001) than the incidence rates for quintiles 1, 2, 3 and 4. At the opposite end of the deprivation scale, patients belonging to the least deprived quintile (1) had a significantly lower incidence (p≤0.001)of diagnosed ADHD than patients in any other quintile [9.24 cases per 10,000 PYAR (95% CI 8.72 – 9.80)].Patient-level deprivation data was accessible for 80.5% of English ADHD patients (n=6,424).In 4,476 of these patients, their patient-level IMD quintile was either the same as their practice-level quintile or higher. That is to say, in 69.7% of instances patients were either as deprived as their practice-level IMD suggested, or more deprived.

In the other three nations of the UK, evidence for an association between deprivation and ADHD was somewhat weaker (see Figure 4). In Scotland (as in England) patients belonging to practices in the most deprived areas (IMD quintile 5) had the highest incidence of diagnosed ADHD; rates were significantly higher (p≤0.001)than those in the less deprived quintiles(quintiles 1, 2, 3 and 4). In Wales, patients in the most deprived quintile had the highest incidence of ADHD, significantly higher (p≤0.001) than that observed in the least deprived quintile. In Northern Ireland, there was no clear association between ADHD and deprivation.

Discussion

This study found that there were statistically significant differences in ADHD incidence rates between the UK’s constituent nations, and between individual regions within England. The finding of significant geographical differences within the UK is probably unsurprising. In the United States, significant differences in diagnostic and treatment rates have been observed between states, and between different communities within the same state (Fulton et al., 2009; McDonald & Jalbert, 2013). Furthermore, Rowlingson et al. (2013) had observed regional variations in methylphenidate prescribing in England that had suggested such variations might be present. That study identified a notable area in the South East of England where medical practices’ methylphenidate spending was four times the national average; this study found that the CPRD’s South East Coast region had the highest ADHD incidence rate of all CPRD regions.

It may be the case that these differences in diagnostic rates are explicable by national and regional differences in diagnostic and management procedures. All areas of the UK would be expected to take the 2008 National Institute for Health and Care Excellence (NICE) guidance on the diagnosis and management of ADHD as a primary resource. However, it is possible that a child diagnosed with ADHD in one part of the UK may not have had the disorder recognised and diagnosed had they lived in another part of the country. All four constituent nations of the UK have distinct budgets for healthcare, and must prioritise spending according to national needs and priorities (National Audit Office, 2012). Similarly, different regions within each nation have their own allocated budgets which must be used to provide a well-rounded health service to the local populace. It has been acknowledged that different areas of the UK provide inconsistent levels of service provision for ADHD (National Institute for Health and Care Excellence, 2013), potentially resulting in different levels of case recognition.

Alternatively, the regional and national differences in diagnostic rates may reflect genuine differences in ADHD incidence across the UK. That is to say populations in some parts of the UK may have a higher proportion of individuals with some genetic susceptibility to ADHD and/or higher exposure to environmental risk factors that promote its onset. One environmental factor suggested to play a role in the aetiology of ADHD is sunlight. In 2013, Arns, van der Heijden, Arnold, & Kenemans reported an inverse association between regional solar intensity and ADHD prevalence across 49 US states, and across several countries. That finding has been contested elsewhere (Hoffmann et al., 2014), and this study’s findings did not appear to suggest an association between ADHD and solar intensity in the UK. The South East Coast of England had the highest incidence of ADHD of all English regions, despite its southerly latitude and its relatively high solar intensity (Met Office, 2014). In addition, Scotland had the lowest ADHD incidence of all four UK nations despite being the most northerly and having the lowest solar intensity overall (Met Office, 2014). This does not rule out a relationship between ADHD and sunlight but does suggest that in a country the size of the UK, in the UK’s position geographically, regional differences in ADHD incidence do not appear to be influenced by regional differences in solar irradiation.