East Asian Arch Psychiatry 2010;20:76-86

ORIGINAL ARTICLE

A Prospective Observational Study of Attention- deficit Hyperactivity Disorder in Asia: Baseline Characteristics of Symptom Severity and Treatment Options in a Paediatric Population
一项有关亚洲过度活跃症患者的观察性研究:儿童人口病症的基线特征和治疗选择
F Martényi, Y Zheng, YS Huang, YS Lee, R Walton, G Harrison, T Treuer

Dr Ferenc Martényi, MD, PhD, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, United States.
Mr Yi Zheng, MD, Beijing Anding Hospital, Capital Medical University, Beijing, PR China.
Mr Yu-shu Huang, MD, Department of Psychiatry, Chang Gung Memorial Hospital and University, Taoyuan, Taiwan.
Mr Yong-sik Lee, MD, Department of Psychiatry, Chung-Ang University Medical School, Seoul, Republic of Korea.
Mr Richard Walton, MSc, InterContinental Information Sciences, Eli Lilly Pty Ltd, Sydney, New South Wales, Australia.
Dr Gavan Harrison, PhD, InterContinental Information Sciences, Eli Lilly Pty Ltd, Sydney, New South Wales, Australia.
Dr Tamás Treuer, MD, PhD, Eli Lilly Regional Medical Center, Vienna, Austria.

Address forcorrespondence: Dr Ferenc Martényi, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, United States.
Tel: (1-317) 277-1564; Email:martenyife@lilly.com

Submitted: 14 December 2009; Accepted: 11 March 2010


pdf Full Paper in PDF

Abstract

Objectives: To better understand the burden and management of attention-deficit hyperactivity disorder in East Asia, this subanalysis of the baseline characteristics of a large prospective, observational, non- randomised study investigating the relationships between symptom severity, treatments, co-morbidities, and health outcomes provides information about the diagnosis of, and treatment patterns for, attention- deficit hyperactivity disorder in this region.

Methods: Outpatients with attention-deficit hyperactivity disorder symptoms participated in this 12- month study performed in China, Korea, and Taiwan. Patients were grouped according to whether they received conventional treatment or no or other treatment. Attention-deficit hyperactivity disorder symptom severity and co-morbidities were assessed using the Clinical Global Impressions–Attention-deficit Hyperactivity Disorder–Severity scale and Child Symptom Inventory-4: Parent Checklist (categories B to J) / Adolescent Symptom Inventory-4: Parent Checklist (categories L and O), respectively.

Results: A total of 502 patients aged 6 to 18 years were enrolled. Investigators were psychiatrists (69%) and paediatricians (31%), who used the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (86%), the 10th revision of the International Classification of Diseases (6%), and other attention-deficit hyperactivity disorder diagnostic criteria (8%) for diagnosis. Pharmacotherapy was the most commonly prescribed treatment (n = 251; 50%), and treated patients were older (9.1 vs. 8.2 years; p < 0.001) and more severely ill (Clinical Global Impressions–Attention-deficit Hyperactivity Disorder– Severity scale, 4.6 vs. 4.2; p < 0.001) than those who were not treated. Anxiety and oppositional co- morbidities were commonly reported.

Conclusions: These data provide an insight into the demographics, diagnosis, and treatment of paediatric patients with attention-deficit hyperactivity disorder in East Asia, and provide a baseline for assessing changes in treatment practices in this population.

Key words: Asia; Attention deficit disorder with hyperactivity; Diagnosis; Quality of life; Therapeutics 

摘要

目的: 为进一步了解东亚地区过度活跃症的各类负担和治疗发展,作者进行一项大型预期观察 性非随机研究的基线特征次组分析,并透过检视症状严重度、治疗、并存疾病和健康果效之间 的关系,描述有关地区过度活跃症的诊断和治疗模式。

方法: 参与这项为期12个月研究的包括中国、韩国和台湾出现过度活跃症症状的门诊病人。 患者被分为三组:曾接受常规治疗、从未接受治疗,或曾接受其他治疗。 研究透过临床总体 印象过度活跃症严重度量表,以及儿童症状量表-4(家长鉴定版)B至J类项目 / 青年症状量 表-4(家长鉴定版)L和O类项目,分别对过度活跃症症状严重度和并存疾病作出评估。

结果: 共502名6至18岁的患者参与研究。 包括精神科(69%)和儿科(31%)医生的研究人员 使用精神疾病诊断与统计手册第四版(86%)、国际疾病分类法第十版(6%),以及其他工具 (8%)作为过度活跃症诊断标准。 药物治疗是最普遍治疗方法(n = 251; 50%);与从未接受 治疗的患者比较,曾接受治疗的患者年龄较大(9.1对8.2岁; p < 0.001),病情也较严重(临床 总体印象过度活跃症严重度量表得分,4.6对4.2; p < 0.001)。 研究也指出不少患者存有焦虑和 对立性共存疾病。

结论: 研究数据有助了解东亚地区过度活跃症儿童患者的人口统计学、诊断和治疗进展,也是评估治疗模式改革的基线。

关键词:亚洲、过度活跃症、诊断、生活质素、疗法

Introduction

Attention-deficit hyperactivity disorder (ADHD) is a relatively common psychiatric condition in children and adolescents that is estimated to occur in approximately 3 to 10% of school-aged children worldwide.1 However, the prevalence rates appear to vary substantially2; in the US, estimates range from 5 to 10%,3-5 whereas in Europe, ADHD is reported to affect approximately 4 to 18% of school-aged children.3

Data on the prevalence of ADHD in Asia are limited, although the prevalence has been suggested to be similar to that of western countries.6,7 In Taiwan, it is estimated that 7.5 to 10% of the paediatric population has ADHD, while in Japan, approximately 8% of school-aged children are reported to have the condition.6-9 Hyperactivity was found to affect 9% of schoolboys in Hong Kong,10 and a Korean study11 suggested that ADHD may affect up to 12% of adolescent non-delinquent children. Regional differences in reported prevalence rates could reflect the variable methodological tools used to assess ADHD, or cross- cultural differences in disease recognition.2,12,13

In the US and other countries, diagnoses are made using the 4th edition of American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) classification of ADHD.14,15 European countries tend to use the 10th revision of World Health Organization’s International Statistical Classification of Diseases and Related Health Problems (ICD-10) hyperkinetic disorder (HKD) criteria,16 which generally corresponds with those classified by the DSM-IV.16 There are differences in the categorisation of symptomatic ADHD behaviours between the DSM-IV and ICD-10 diagnostic criteria, and establishing a diagnosis can therefore vary.2,17,18 Although studies have demonstrated the validity of western diagnostic criteria for ADHD in Asian countries, limitations remain, suggesting that there are differences in how ADHD is diagnosed between cultures.13,19 Disease prevalence can also vary between ethnic groups.20

Up to 50% or more of ADHD patients may present with psychiatric co-morbidities or learning disabilities in western countries,18,21-23 and increasing severity of ADHD is associated with poor health-related quality of life (QoL).24,25 Treatment plans for ADHD should therefore aim to reduce symptoms, enhance functionality, and improve individual well-being.26 Information on how ADHD is treated in Asia is limited, and data on ADHD co-morbidities in the region are also scarce.7,23,27 There is a need to further understand treatment practices for ADHD in the region and to identify factors that influence the management of ADHD, which may help inform effective treatment strategies.

This study represents a subanalysis of the baseline characteristics of a large prospective, observational, non- randomised study designed to provide information about the diagnosis of, and treatment patterns for, ADHD in lesser studied parts of the world, including Central and East Europe (CEE) and East Asia.28 Given that there is a gap in the current knowledge of ADHD treatment practices and the impact of ADHD on patients’ QoL in these regions, this subanalysis attempted to redress the balance of information by describing treatment regimens as prescribed in real-life clinical settings, in a large and diverse paediatric population from East Asia (China, Korea, and Taiwan). In addition, the subanalysis evaluated the relationship between demographics, severity of ADHD symptoms, co-morbidities, functional status, and QoL, as well as the criteria used to diagnose the illness, and treatment patterns and correlates at study initiation (baseline).

Methods

Patients

Patients eligible for enrolment were male and female children or adolescent outpatients aged 6 to 18 years who had ADHD symptoms and presented to a physician, and had not been previously diagnosed with or treated for ADHD. Investigators were asked which diagnostic criteria (DSM-IV ADHD or ICD-10 HKD) they used but a formal ADHD or HKD diagnosis was not required. Patients were not eligible for enrolment if they had severe mental retardation, epilepsy, or schizophrenia, or were participating simultaneously in a different study that included a treatment intervention and / or an investigational drug. Written informed consent was obtained from the parent or guardian of the patients before entry into the observational study.

Study Design

This was a 12-month, prospective, non-randomised observational study designed to understand the relationship between physician-prescribed treatment regimens and QoL of patients with ADHD symptoms in clinical practice.28 Enrolment was initiated on 17 December 2005, with the last patient visit on 12 October 2007. At the first visit, patients were assessed for study eligibility, and initial observations and measurements were recorded. Patients were enrolled from 16 sites across East Asia; 8 in China, 5 in Korea, and 3 in Taiwan, involving 16 paediatricians and psychiatrists who were selected on the basis of past experience in treating ADHD.

Ethical Review Board approval was obtained as required for observational studies wherever required by local law, and the study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was consistent with Good Clinical Practice where applicable to a study of this nature.

Treatment Groups

Patients with ADHD could be prescribed any treatment regimen by the physician. Treatment decisions were at the sole discretion of the physicians, patients, or parents / guardians and were independent of study participation. Patients were grouped according to the following 5 treatment categories for analysis of the treatment regimen prescribed at baseline: (1) no treatment, (2) psychotherapy, (3) pharmacotherapy (any drug treatment targeting ADHD symptoms), (4) combined psychotherapy / pharmacotherapy, or (5) other treatments. The no-treatment group included patients receiving no intervention at baseline assessment. Psychotherapy was considered as formal sessions (in the opinion of the investigator) of psycho-education and counselling, cognitive behavioural therapy, hypnotherapy, family therapy, or psychodynamic therapy conducted by a certified health care provider at a regular frequency for an acceptable treatment duration. Other treatments included educational interventions, speech therapy, occupational therapy, herbal therapy / homeopathy, informal hypnosis, psychomotor / physiotherapy, electroencephalography biofeedback, diet exclusion, diet supplementation, and relaxation techniques.

For the major analytic comparisons, patients were separated into 2 groups: treatment (psychotherapy and / or pharmacotherapy) group and no- / other-treatment (no treatment or other treatment only) group. If other therapies were prescribed in combination with pharmacotherapy and / or psychotherapy, patients were included in the relevant treatment group. No concomitant medications were excluded from the study and data on concomitant medications were recorded.

Measures

Demographic data of enrolled patients, including age, sex, educational status, family structure, and family history of ADHD were recorded together with the type of diagnostic criteria employed (DSM-IV, ICD-10, or other). Clinical severity of ADHD symptoms was measured using the Clinical Global Impressions–Attention-deficit Hyperactivity Disorder–Severity (CGI-ADHD-S) scale and Category A (Cat A) of the Child Symptom Inventory–4: Parent Checklist (CSI-4).29,30 The CSI-4 scores were recorded by the treating physician in consultation with parents; Cat A was also used to support the diagnosis of ADHD based on the DSM-IV criteria, whereby a score of >6 in either the inattentive and / or hyperactive / impulsive domains was considered supportive of the ADHD diagnosis. Parent-rated CSI-4 scores were verified by the treating physicians, who also recorded their own ratings.

Co-morbidities of ADHD were assessed both by parents and physicians using categories B to J of the CSI-4 scale and categories L and O of the Adolescent Symptom Inventory-4: Parent Checklist (ASI-4).29,31 Symptom severity scores were calculated for each category and used to determine screening cut-off scores that supported diagnostic assessments of these conditions.

Quality of life was assessed using the Parent Report Form of the Child Health and Illness Profile–Child Edition (CHIP-CE / PRF).32 Academic, social, and other health care outcomes, and use of concomitant medications were assessed by parent- / guardian-solicited questionnaires.

Statistical Analyses

All patient data were analysed unless the enrolment criteria were violated, and any records containing missing data were excluded from the analysis. Continuous data were reported using total number observed, mean and standard deviation (SD) or median with minimum and maximum. These data were analysed using a 2-sample t test for the 2- group treatment cohort (treatment vs. no / other treatment), and an F test for the 5-group regimens (psychotherapy, pharmacotherapy, psychotherapy / pharmacotherapy, other treatment, and no treatment). Categorical variables were reported using frequency and percentage, and were compared using Fisher’s exact test; patients with missing data were not included in the denominator. Baseline differences across the 5-group cohort were assessed using 1-way analysis of variance for continuous variables and Chi-square test for categorical variables. A 2-sided significance level of 0.05 was specified.

In consideration of the design (observational, non- randomised) and objectives of this study, the sample size estimation was based on achieving a desired precision (according to the 95% confidence interval width) of the potential between-group difference for change in the primary outcome of interest (CHIP-CE / PRF scores) and further inflated for expected dropout over the 12 months’ duration of the study in CEE and East Asia.28 Enrolment of 1100 patients into the study was targeted a priori to allow detection of group differences, with a 95% confidence interval of width 5.2 units (2.6 units in either direction) on the individual CHIP- CE domain scores under the following assumptions: SD for change from baseline to 12-month endpoint in CHIP-CE scores of 12; ratio of treatment — no- / other-treatment group sizes of 10:1; and 10% dropout rate, leaving approximately 1000 evaluable patients at the end of the study. This sample size was intended to allow for modest deviation from the estimated parameters and also some scope for regional and country-level subanalyses, while still providing for meaningful interpretation. The sample size justification was based on the specified primary endpoint at 12 months.

Results

The baseline results are for the Asian countries subgroup.

Baseline Demographics and Patient Characteristics

A total of 502 eligible patients were enrolled in the East Asia substudy, of whom 301 (60%) were from China, 100 (20%) from Korea, and 101 (20%) from Taiwan (Table 1). The mean age of the patients was 8.9 years, the majority of whom were male (83%), and 61% of patients were the only child at home. China reported the highest proportion of patients who were the only child at home (87%). A family history of ADHD symptoms was reported for 28% of patients, with higher rates observed in China (29%) than in Korea (26%) or Taiwan (24%) [Table 1].

Diagnosis

Most (86%) ADHD diagnoses recorded in this region were based on DSM-IV criteria, 6% on the ICD-10 criteria, and 8% on other ADHD diagnostic criteria (Figure 1). When analysed separately, all Korean patients, 87% of Chinese patients, and 66% of Taiwanese patients were diagnosed according to the DSM-IV criteria. In Taiwan, all non– DSM-IV diagnoses were made using the ICD-10 criteria, which accounted for 34% of diagnoses. China was the only country to adopt other criteria for ADHD diagnosis, which accounted for 13% of patients.

The DSM-IV criteria were adopted for a higher proportion of non-treated patients than for patients prescribed treatment (93% vs. 84%; p = 0.002), although DSM-IV criteria were also the primary diagnostic tool used in the treatment cohort (Figure 1).

The DSM-IV and ICD-10 diagnoses were supported by positive physician-rated CSI-4 (Cat A) screening scores for all ADHDs in 85% and 86% of patients, respectively (Table 2). There was no difference between the diagnostic criteria used and the proportion of patients diagnosed with either ADHD-hyperactive / impulsive (ADHD-HI) or ADHD-combined (ADHD-C) types, although the proportion of patients with positive CSI-4 screening cut-off scores for ADHD-inattentive (ADHD-I) type was significantly higher with DSM-IV than with ICD-10 criteria (38% vs. 24%; p = 0.01). Conversely, patients diagnosed using ICD-10 criteria demonstrated higher rates of positive screening cut-off scores for ADHD-HI than those diagnosed using DSM-IV (17% vs. 8%), although not statistically significant (p = 0.15) [Table 2].

Treatment Groups

Overall, 70% of patients received treatment and 30% were prescribed no / other treatment (Figure 2). Treated patients were older than those not treated or treated by other means (mean age, 9.1 years vs. 8.2 years; p < 0.001).

Pharmacotherapy was the most commonly prescribed treatment, being administered to 50% of patients. Combined psychotherapy / pharmacotherapy was prescribed for 12% of patients, while 8% received psychotherapy alone. No treatment was prescribed for 19% of patients, and 11% were prescribed other treatment only (Figure 2). In China, pharmacotherapy was prescribed to 67% of patients, and was by far the most commonly prescribed therapy. Combined pharmacotherapy / psychotherapy was the most commonly prescribed treatment in Korea (38%), and psychotherapy was the primary treatment prescribed in Taiwan (27%) [Figure 2].

As shown in Table 3, methylphenidate (94%) was the most commonly prescribed medication for patients receiving pharmacotherapy, and psycho-education / counselling (93%) was the most common form of psychotherapy. Most (76%) patients being prescribed other therapies received educational intervention.

Treatment by Medical Specialty

Psychiatrists were responsible for most of the diagnoses and treatments prescribed (n = 345; 69%) compared with paediatricians (n = 157; 31%; p < 0.001). In Taiwan and Korea, all treatments were prescribed by psychiatrists whereas in China, 48% of patients (n = 144) were prescribed by psychiatrists and 52% (n = 157) by paediatricians.

Clinical Status and Severity

Overall, patients demonstrated moderate-to-marked ADHD symptoms with a mean CGI-ADHD-S score of 4.5 (SD, 1.0), and a mean CSI-4 (Cat A, raw scores) of 31.4 (SD, 9.2). The mean CGI-ADHD-S score of treated patients was 4.6 (SD, 1.0), which was statistically significantly higher than that of patients in the no- / other-treatment group (4.2 [0.9]; p < 0.001; Figure 3).

In the treatment group, patients receiving psychotherapy appeared more markedly ill than those prescribed other treatment regimens, with a mean CGI- ADHD-S score of 5.2, compared with 4.7 for the combined psychotherapy / pharmacotherapy group (p = 0.001). The mean (SD) CGI-ADHD-S scores in the pharmacotherapy, other therapy, and no-treatment groups were 4.5 (1.0), 4.5 (0.9), and 4.0 (0.9), respectively.

Co-morbidities

Differences in the degree of positive CSI-4 or ASI-4 screening cut-off scores for patients who were diagnosed using DSM-IV, ICD-10, or other criteria were observed for oppositional defiant disorder (ODD), obsessions, compulsions, major depressive disorder (MDD), dysthymic disorder, schizophrenia, and bipolar disorder (Table 2).

Specific phobia was the most commonly reported co- morbidity with a positive CSI-4 screening cut-off score in both the treatment and no- / other-treatment groups (53%), followed by vocal tics (41%), motor tics (39%), and ODD (37%). Other common co-morbidities (> 20% of patients meeting the CSI-4 screening cut-off) included obsessions and post-traumatic stress disorder (Table 4).

A higher proportion of treated patients had positive CSI-4 screening cut-off scores for all ADHDs and ADHD-C symptoms than patients in the no- / other-treatment group. However, there was no statistically significant difference in the proportion of patients with positive screening cut-off scores for ADHD-HI or ADHD-I between either treatment group (Table 4).

Quality of Life

No significant differences in mean CHIP-CE scores were observed between treatment groups in the 5 domains of satisfaction, comfort, risk avoidance, resilience, and achievement (Figure 4). Overall mean (SD) scores in the CHIP-CE domains of satisfaction, risk avoidance, resilience, and achievement were 32.3 (14.2), 34.6 (12.2), 30.2 (12.4), and 29.4 (9.8), respectively. The overall mean (SD) score for the CHIP-CE domain of comfort was 44.3 (10.2).

Social Functioning

Overall, no differences were reported for most social functioning and health outcome domains across both treatment groups. A higher proportion of treated patients visited a primary care physician for behavioural problems or was invited to a social activity in the 4 weeks prior to the baseline assessment (Table 5).

Discussion

This study was conducted to investigate the relationship between physician-prescribed treatment regimens and QoL of children and adolescents with ADHD symptoms in clinical practice over a 12-month period in China, Korea, and Taiwan. In general, the baseline data presented here reflect observations of clinically referred ADHD patient samples reported in western countries, in that there was a gender bias toward males, and patients reported a high level of co-morbidity with significant impairment in QoL. Anxiety disorders were the predominant co-morbidities reported, with particularly high rates of specific phobia and vocal / motor tics observed. The DSM-IV was the main diagnostic criteria used overall, but there was some inter-country variation in using ICD-10 and other criteria. Patients being prescribed treatment were significantly older and more severely ill than those receiving no / other treatment, and the proportion of patients diagnosed with ADHD-HI or ADHD-C subtypes was similar using either DSM-IV or ICD-10 criteria. This study also demonstrated inter-country and regional variations in ADHD treatment practices, suggesting that cultural factors may play a role in management decisions for ADHD.

In this study group, most patients in the East Asia region were male, which is congruent with the literature supporting a higher prevalence of ADHD in males, particularly in clinically referred populations.4,6,9,18,27 Sex- based referral bias that is unfavourable towards young females — who are less likely to manifest disruptive hyperactive ADHD symptoms than young males — has been reported in the literature.33,34 Cultural factors have been suggested to influence the recognition of hyperactive symptoms in children in East Asia.13,27

Most patients were diagnosed using DSM-IV rather than ICD-10 criteria, although the utilisation rates of these diagnostic tools varied considerably across the region. Diagnoses in Korea were based exclusively on DSM-IV criteria and ICD-10 criteria were used in Taiwan only. China was the only country to use other criteria, which primarily included the Chinese Classification of Mental Disorders,35 although the majority of diagnoses were based on DSM- IV criteria. This variability could, in part, be a consequence of the normal practices of the treating physician, although cultural factors may also be important. In Korea and Taiwan, all diagnoses were made and treatments prescribed by psychiatrists, whereas paediatricians were involved in more than half of diagnoses and treatment decisions in China. However, it is important to recognise that the preponderance towards psychiatrists as the treating physician in this study may reflect investigator recruitment rather than actual practice.

The ADHD diagnoses using any criteria (DSM-IV, ICD-10, or other) were supported by a positive CSI-4 screening score for most patients. Patients diagnosed using DSM-IV criteria demonstrated higher rates of positive CSI-4 screening scores for the ADHD-I subtype, which may reflect nosological differences between the ICD-10 and DSM-IV criteria in terms of their categorisation of ADHD subtypes.17,18

Most patients in this study were prescribed conventional treatment for ADHD at baseline, primarily in the form of pharmacotherapy and / or psychotherapy. Methylphenidate was the most commonly administered pharmacotherapy in the region, reflecting the dominance of stimulant medications in the pharmacological management of ADHD.21,36,37 Psycho-education / counselling was the most common psychotherapy administered, and the relatively high overall prescription rates of combined psychotherapy / pharmacotherapy reported in this study suggest that multimodal management is a core strategy for ADHD treatment in East Asia. However, there were noticeable inter-country variations in the types of treatment prescribed.

Overall, patients were moderately-to-markedly ill, although treated patients reported more severe inattentive and hyperactive / impulsive ADHD symptoms than those who were not prescribed conventional therapy. Mean CGI- ADHD-S scores in the treatment group were higher than that in the no- / other-treatment group, but the clinical significance of these data is unclear.

Co-morbidities of ADHD were common in this study, which is in agreement with other published reports.8,9,20,21,27,37-41 Overall, the most common co-morbidities were specific phobia, vocal tics, motor tics, and ODD. This is in contrast to studies that ODD and conduct disorder (CD) were the most frequently reported co-morbidities.19- 21,42 Recent studies reported ODD in 61.7% of patients with ADHD in the UK and 40.6% in the US.37,43 Approximately 20 to 56% of individuals with ADHD may present with CD,42 although 14.3% of patients presented with co-morbid CD in the multimodal treatment of ADHD study,44 which is closer to the 15% reported in this study. Of particular note is the high frequency of co-morbid vocal and motor tics in this population, which has not been reported elsewhere.

The predominance of co-morbid specific phobias in this study is also a novel finding. Specific phobias are rarely reported in ADHD, but up to 25% of patients with ADHD may present with anxiety disorders,40 which draws attention to the high rates of specific phobia reported here. Most ADHD co-morbidity data come from western studies, and few cross-cultural studies on ADHD co-morbidities have been conducted in East Asia. A recent study in Japan7 reported a high prevalence of specific phobia in ADHD and a higher rate of anxiety disorders relative to western studies, although ODD was the most commonly reported ADHD co- morbidity in a Korean study.27

While these findings are of interest, it is important to note that the CSI and ASI are behaviour rating scales that do not provide qualifying criteria such as functional impairment and age of onset. As such, these tools do not allow a formal diagnosis and may overestimate the prevalence of co-morbidities in this study relative to formal clinical diagnoses used in other studies.

The QoL of all patients in this study — irrespective of treatment group — was low in the satisfaction, risk avoidance, resilience, and achievement domains. This suggests that patients experienced poor health-related QoL in the 4 weeks prior to the baseline assessment,45 which is in accordance with other studies demonstrating low health- related QoL in individuals with ADHD.14,26,46 Although not tested statistically, differences between the treatment groups in the CHIP-CE domains were small and not likely to be clinically meaningful (Figure 4).

While it is clear that many of the patients enrolled in this study experienced poor QoL, there was no significant difference observed in social functioning between either treatment group. However, a significantly higher proportion of patients prescribed treatment had visited a primary care physician for behavioural problems in the 4 weeks prior to the baseline assessment, which may be expected in a population with more markedly severe ADHD symptoms. Contrary to this observation, a higher proportion of patients in the treatment group were invited to a social activity 4 weeks prior to the initial visit than those in the no- / other-treatment group, which may be unexpected for this population.

There are limitations to this study that should be acknowledged when interpreting these observational data. While the naturalistic and non-interventional design allowed the inclusion of patients who may have been ineligible for clinical trials, the lack of randomisation and blinding may have introduced biases and imbalances between patient groups, as investigators tailored treatment to individual patient profiles.28 Moreover, the sampling may still not be entirely representative due to the possibility of preferential selection or refusal of patients with certain characteristics to enter the study. However, in this baseline analysis, it is for these reasons (open-label / lack of randomisation) that patient characteristics associated with each treatment group are informative, as they reflect the investigators’ real-life treatment decisions based on individual patient characteristics. Another important consideration is that analyses in this substudy are powered at the overall level for a study investigating treatment practices in CEE and East Asia, in which the primary objective was the change in CHIP-CE scores after 12 months.28 Subanalyses, such as reported here, may therefore have less power to detect baseline differences between groups, and are also not corrected for national characteristics. Furthermore, the study cannot be assumed to be representative of the general paediatric ADHD population of East Asia, as it included only those patients whose symptoms and impairment were of sufficient severity to warrant clinical referral. Moreover, formal diagnoses of ADHD and its co-morbidities were not conducted, but were based on symptom ratings, which could have led to overestimation of their prevalence. The selection of participating physicians was also pragmatic rather than representative.

In conclusion, the baseline findings of this study make a significant contribution toward improving the understanding of ADHD and its management in East Asia. The patients will subsequently be followed up for a further 12 months to observe changes in QoL in relation to different treatment strategies. These data provide an insight into current treatment practices for ADHD in an understudied region, and further study of this population may help improve the clinical knowledge, treatment, and outcomes of ADHD.

Acknowledgements

This research was sponsored by Eli Lilly and Company Ltd, Indianapolis, USA. Writing and editorial support for this manuscript was provided by MediTech Media Asia Pacific Pte Ltd, Sydney, Australia. Ferenc Martényi, Tamás Treuer, Richard Walton, and Gavan Harrison are employees of Eli Lilly. Yi Zheng, Yu-shu Huang, and Yong-sik Lee have no conflicts of interest to disclose.

References

  1. Prince JB. Pharmacotherapy of attention-deficit hyperactivity disorder in children and adolescents: update on new stimulant preparations, atomoxetine, and novel Child Adolesc Psychiatr Clin N Am 2006;15:13-50.
  2. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007;164:942-8.
  3. Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2003;2:104-13.
  4. Froehlich TE, Lanphear BP, Epstein JN, Barbaresi WJ, Katusic SK, Kahn RS. Prevalence, recognition, and treatment of attention-deficit / hyperactivity disorder in a national sample of US children. Arch Pediatr Adolesc Med 2007;161:857-64.
  5. Gadow KD, Nolan EE, Litcher L, Carlson GA, Panina N, Golovakha E, et al. Comparison of attention-deficit / hyperactivity disorder symptom subtypes in Ukrainian schoolchildren. J Am Acad Child Adolesc Psychiatry 2000;39:1520-7.
  6. Gau SS, Chong MY, Chen TH, Cheng A 3-year panel study of mental disorders among adolescents in Taiwan. Am J Psychiatry 2005;162:1344-50.
  7. Takahashi K, Miyawaki D, Suzuki F, Mamoto A, Matsushima N, Tsuji H, et Hyperactivity and comorbidity in Japanese children with attention-deficit / hyperactivity disorder. Psychiatry Clin Neurosci 2007;61:255-62.
  8. Gau SS, Huang YS, Soong WT, Chou MC, Chou WJ, Shang CY, et A randomized, double-blind, placebo-controlled clinical trial on once- daily atomoxetine in Taiwanese children and adolescents with attention- deficit / hyperactivity disorder. J Child Adolesc Psychopharmacol 2007;17:447-60.
  9. Wang YC, Chong MY, Chou WJ, Yang Prevalence of attention deficit hyperactivity disorder in primary school children in Taiwan. J Formos Med Assoc 1993;92:133-8.
  10. Leung PW, Luk SL, Ho TP, Taylor E, Mak FL, Bacon-Shone The diagnosis and prevalence of hyperactivity in Chinese schoolboys. Br J Psychiatry 1996;168:486-96.
  11. Chae PK, Jung HO, Noh Attention deficit hyperactivity disorder in Korean juvenile delinquents. Adolescence 2001;36:707-25.
  12. Mann EM, Ikeda Y, Mueller CW, Takahashi A, Tao KT, Humris E, et Cross-cultural differences in rating hyperactive-disruptive behaviors in children. Am J Psychiatry 1992;149:1539-42.
  13. Norvilitis JM, Fang Perceptions of ADHD in China and the United States: a preliminary study. J Atten Disord 2005;9:413-24.
  14. Diagnostic and statistical manual of mental 4th ed (text revision). Washington, DC: American Psychiatric Press; 2000.
  15. Voeller Attention-deficit hyperactivity disorder (ADHD). J Child Neurol 2004;19:798-814.
  16. The ICD-10 classification of mental and behavioural disorders: clinical description and diagnostic guidelines 1992; diagnostic criteria for research 1993. Geneva: World Health Organization; 1993.
  17. Lahey BB, Pelham WE, Chronis A, Massetti G, Kipp H, Ehrhardt A, et Predictive validity of ICD-10 hyperkinetic disorder relative to DSM-IV attention-deficit / hyperactivity disorder among younger children. J Child Psychol Psychiatry 2006;47:472- 9.
  18. Swanson JM, Sergeant JA, Taylor E, Sonuga-Barke EJ, Jensen PS, Cantwell Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet 1998;351:429-33.
  19. Yang L, Wang YF, Qian QJ, Biederman J, Faraone DSM-IV subtypes of ADHD in a Chinese outpatient sample. J Am Acad Child Adolesc Psychiatry 2004;43:248-50.
  20. Nolan EE, Gadow KD, Sprafkin Teacher reports of DSM-IV ADHD, ODD, and CD symptoms in schoolchildren. J Am Acad Child Adolesc Psychiatry 2001;40:241-9.
  21. Goldman LS, Genel M, Bezman RJ, Slanetz Diagnosis and treatment of attention-deficit / hyperactivity disorder in children and adolescents. Council on Scientific Affairs, American Medical Association. JAMA 1998;279:1100-7.
  22. Hechtman Assessment and diagnosis of attention-deficit / hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 2000;9:481-98.
  23. Ishii T, Takahashi O, Kawamura Y, Ohta Comorbidity in attention deficit-hyperactivity disorder. Psychiatry Clin Neurosci 2003;57:457- 63.
  24. Yang P, Hsu HY, Chiou SS, Chao MC. Health-related quality of life in methylphenidate-treated children with attention-deficit-hyperactivity disorder: results from a Taiwanese sample. Aust N Z J Psychiatry 2007;41:998-1004.
  25. Topolski TD, Edwards TC, Patrick DL, Varley P, Way ME, Buesching Quality of life of adolescent males with attention-deficit hyperactivity disorder. J Atten Disord 2004;7:163-73.
  26. Klassen AF, Miller A, Fine S. Health-related quality of life in children and adolescents who have a diagnosis of attention-deficit / hyperactivity disorder. Pediatrics 2004;114:e541-7.
  27. Byun HJ, Yang JW, Lee MS, Jang WS, Yang JW, Kim JH, et Psychiatric comorbidity in Korean children and adolescents with attention-deficit hyperactivity disorder: psychopathology according to subtype. Yonsei Med J 2006;47:113-21.
  28. Martényi F, Treuer T, Gau SS, Hong SD, Palaczky M, Suba J, et Attention-deficit / hyperactivity disorder diagnosis, comorbidities, treatment patterns and quality of life in a pediatric population in central and eastern Europe and Asia. J Child Adolesc Psychopharmacol 2009;19:363-76.
  29. Gadow KD, Sprafkin J. Childhood symptom inventory-4 norms / manual. Stony Brook, New York: Checkmate Plus;
  30. Guy ECDEU assessment manual for psychopharmacology, revised. Bethesda (MD): US Department of Health, Education and Welfare; 1976.
  31. Gadow KD, Sprafkin J. Adolescent symptom inventory 4, screening manual. Stony Brook, New York: Checkmate Plus;
  32. Riley AW, Robertson J, Forrest CB, Green B, Rebok G, Starfield Manual for the child health and illness profile — child edition (CHIP- CE). Baltimore, MD: The Johns Hopkins University; 2001.
  33. Biederman J, Mick E, Faraone SV, Braaten E, Doyle A, Spencer T, et al. Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric Am J Psychiatry 2002;159:36- 42.
  34. Quinn P, Wigal Perceptions of girls and ADHD: results from a national survey. Med Gen Med 2004;6:2.
  35. Chen Chinese classification of mental disorders (CCMD-3): towards integration in international classification. Psychopathology 2002;35:171-5.
  36. Pliszka Pharmacologic treatment of attention-deficit / hyperactivity disorder: efficacy, safety and mechanisms of action. Neuropsychol Rev 2007;17:61-72.
  37. Prasad S, Harpin V, Poole L, Zeitlin H, Jamdar S, Puvanendran K; SUNBEAM Study Group. A multi-centre, randomised, open-label study of atomoxetine compared with standard current therapy in UK children and adolescents with attention-deficit / hyperactivity disorder (ADHD). Curr Med Res Opin 2007;23:379-94.
  38. Alyhari A, Goodman R. The prevalence of DSM-IV psychiatric disorders among 7-10 year old Yemeni Soc Psychiatry Psychiatr Epidemiolol 2008;43:224-30.
  39. Bangs ME, Hazell P, Danckaerts M, Hoare P, Coghill DR, Wehmeier PM, et al. Atomoxetine for the treatment of attention-deficit / hyperactivity disorder and oppositional defiant disorder. Pediatrics 2008;121:e314-20.
  40. Biederman J, Newcorn J, Sprich Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry 1991;148:564-77.
  41. Sciutto MJ, Eisenberg M. Evaluating the evidence for and against the overdiagnosis of ADHD. J Atten Disord 2007;11:106-13.
  42. Barkley RA. Attention deficit hyperactivity disorder: a handbook for diagnosis and treatment. New York: Guildford Press;
  43. Elia J, Ambrosini P, Berrettini ADHD characteristics: I. Concurrent co-morbidity patterns in children and adolescents. Child Adolesc Psychiatry Ment Health 2008;2:15.
  44. A 14-month randomized clinical trial of treatment strategies for attention-deficit / hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry 1999;56:1073-86.
  45. Riley AW, Forrest CB, Starfield B, Rebok GW, Robertson JA, Green The Parent Report Form of the CHIP-Child Edition: reliability and validity. Med Care 2004;42:210-20.
  46. Escobar R, Soutullo CA, Hervas A, Gastaminza X, Polavieja P, Gilaberte I. Worse quality of life for children with newly diagnosed attention-deficit / hyperactivity disorder, compared with asthmatic and healthy children. Pediatrics 2005;116:e364-9.
View My Stats