跨越雙障 – 認識智障兼過度活躍症(ADHD) 人士的發展需要 診斷與藥物治療 黄宗顯 精神科專科醫生 英國皇家精神科醫學院院士 香港精神科醫學院院士 香港醫學專科學院院士(精神科) 香港大學李嘉誠醫學院名譽臨床助理教授 2014年10月18日 All rights reserved. This powerpoint is protected by copyright. CONFIDENTIAL

雙障是否存在? 智障 +多動症 = 雙障 有初步證據表明，多動症在智障兒童中是有效的精神診斷 智障 +多動症  易出現認知功能某些方面的缺失 References: Antshel, K.M., Phillips, M.H., Gordon, M., Barkley, R., & Faraone, S.V. (2006) Is ADHD a valid disorder in children with intellectual delays? Clinical Psychology Service, 26, 555-572. Rose, E., Bramham, J., Young, S., Paliokostas, E., Xenitidis, K. (2009) Research in Developmental Disabilities, 30, 496-502. CONFIDENTIAL

雙障 (兒童) 智障兒童處於多動症增加的風險 興奮劑藥物可能成功治療症狀 年齡較小的兒童，自閉症的診斷，有更多的多動症的症狀 Reference: Hastings, R.P., Beck, A., Daley, D., & Hill, C. (2005). Symptoms of ADHD and their correlates in children with intellectual disabilities. Research in Developmental Disabilities, 26, 456-468.

雙障 (青少年) 智障青少年繼續處於多動症增加的風險 智障青少年 + 多動症：智障青少年風險比 3.38：1 智障青少年和非智障青少年多動症症狀的出現相似 Reference: Neece, C.L., Baker, B.L., Crnic, K., & Blacher, J. (2013). Examining the validity of ADHD as a diagnosis for adolescents with intellectual disabilities: clinical presentation. Journal of Abnormal Child Psychology, 41, 597-612.

Introduction to ADHD 什麼是ADHD

Symptoms of ADHD 徵狀 Inattention 專注力不足 Hyperactivity 過度活躍 Impulsivity 衝動行為 The core symptoms of ADHD as defined in the DSM-IV and ICD-10 diagnostic criteria are inattention, impulsivity and hyperactivity The differences between these diagnostic criteria will be outlined later.

ADHD brief definition 簡單定義 Disorders characterized by levels if inattention, hyperactivity and impulsivity that are inconsistent with the level of development of the child, adolescent or adult 小朋友、青少年或成年人如果出現與他們的成長期不相乎的專注力問題、過度活躍和衝動行為‚ 便有可能患上 ADHD 。

ADHD brief definition簡單定義 Symptoms persisted for at least 6 months 徵狀最少持續6個月 Symptoms present before the age of 12 years 徵狀於12歲前出現 Criteria must be met in more than 2 situation (at home, school, or work, with friends or relatives ) 必須在多於2個環境下符合以上徵狀準則 (在家, 學校, 工作間, 與朋友及親友相處) Clinically significant distress or impairment in social, academic or occupational functioning 影響到社交、學業或工作 Maladaptive and inconsistent with developmental level 與正常人發展程度不相符 Data extracted from DSM-V criteria

...they can be extremely intelligent CORE SYMPTOMS 主要徵狀 …but they can also have many strengths 但其實ADHD 的小朋友都有很多不同的長處 Educational intent: to indicate that children with ADHD may exhibit positive types of behaviour too, helping to compensate for their core symptoms   SPEAKERS’ NOTES Mention famous sufferers if you wish. Open-minded 持開放態度 Excitable 時常都興奮 Energetic 充滿活力 Fun to be with 與他們相處很有趣 ...they can be extremely intelligent …他們可以是”超級聰明”的 Döpfner et al 2000, 2002

DSM-V Diagnostic Criteria DSM-V 斷症準則 Inattention Symptoms (at least 6 symptoms required) 專注力不足徵狀 (最少符合6項,成人最少符合 5 項) Fails to give close attention to details or makes careless mistakes in schoolwork, work, etc. 難以注意細節，容易因此犯錯 Difficulty sustaining attention 難以長時間專注於同一件事情，如：學習、日常活動、遊戲 Does not seem to listen when spoken to directly 難以細心聆聽別人的說話 Does not follow through on instructions and fails to finish schoolwork, chores, etc. 難以按照指引做事，經常無法完成日常事務 Difficulty organizing tasks and activities 做事經常缺乏條理，難以妥善安排如有關學習、活動、生活等方面的計劃 Avoids tasks requiring sustained mental effort 抗拒或不喜歡那些需要全神貫注的事情 Loses things necessary for tasks or activities 經常遺失日常學習或活動的所需用品 Easily distracted by extraneous stimuli 很容易受週遭環境或事情影響而分心 Forgetful in daily activities 常遺忘日常生活中已安排的活動，如忘記約會的時間 CONFIDENTIAL

ADHD Diagnostic Criteria (cont.) DSM-V 斷症準則(續) Hyperactivity-Impulsivity Symptoms 過度活躍、衝動行為徵狀 (at least 6 symptoms required)(最少符合6項, 成人最少符合5 項) Difficulty playing or engaging in activities quietly 難以安靜地遊玩或參與休閒活動 Always "on the go" or acts as if "driven by a motor” 無時無刻也在活動，像一部不會停下來的機器 Talks excessively 多言 Blurts out answers 問題還未問完，他們便搶著回答 Difficulty waiting in lines or awaiting turn 難以在遊戲或群體中輪候或排隊 Interrupts or intrudes on others 常中途打擾或騷擾別人的活動 Runs about or climbs inappropriately 在不適當的場合四處跑或攀爬 Fidgets with hands or feet or squirms in seat 常手舞足蹈，或在座位上不停地扭來扭去，難以安靜下來 Leaves seat in classroom or in other situations in which remaining seated is expected 在課室或需要安坐的場合，經常擅自離座 CONFIDENTIAL

ADHD Diagnostic Criteria (cont.) 斷症準則(續) Symptoms present before age 12 徵狀於12歲前出現 Clinically significant impairment in social or academic/occupational functioning 影響到社交、學業或工作 Some symptoms that cause impairment are present in 2 or more settings (e.g., school/work, home, recreational settings) 在兩個平時活動的 2個或以上範疇出現症狀 Not due to another disorder (e.g., Mood Disorder, Anxiety Disorder) 出現的症狀並非由其它病引致的 (例:情緒失調、焦慮症) CONFIDENTIAL

DSM-V DIAGNOSES (ADHD) ADHD CLASSIFICATION分類 DSM-V DIAGNOSES (ADHD) Combined Type複合型 Clinical levels of both inattention and hyperactivity/impulsivity臨床 同時出現 “專注力失調”和“過度活躍/ 衝動型” Most common subtype最常見的類型 Predominantly Inattentive Presentation 專注力不足型 Clinical levels of inattention only 臨床只有專注力不足型 Often not identified until middle school 通常要到中學時期才被發現 Sluggish cognitive tempo 認知速度遲緩 Predominantly Hyperactive/Impulsive Presentation 過度活躍 / 衝動型 Clinical levels of hyperactivity/impulsivity only 臨床出現過度活躍或衝動型 More common among very young children prior to school entry 普遍見於未入學的幼童 (於香港 / 澳門剛入小學的時候) CONFIDENTIAL

Diagnostic Issues in DSM – V (For adolescents and adults) For the diagnosis of adolescents and adults:青少年和成人的診症: For older adolescents and adults (age 17 and older), at least five symptoms are required. 對於青少年和成人(17歲及以上)‚ 最少需符合5個徵狀 Several inattentive or hyperactive – impulsive symptoms were present prior to age 12 years. 於12歲前, 巳出現有數個專注力失調 或過度活躍 / 衝動型的徵狀 In adults, hyperactivity may manifest as extreme restlessness or wearing others out with their activity 就成人來說‚ 過度活躍可以是極度坐立不安或煩擾他人的行為 (未必一定是如小童般過動) Impulsivity may manifest as social intrusiveness (e.g., interrupting others excessively) and/ or as making important decisions without consideration of long term consequences (e.g., taking a job without adequate information). 衝動行為能被視為干擾社交的行為(例:過份地打擾他人)和/或未考慮長遠後果而作出重要決定 (例:接受一份未了解工作性質的工作) CONFIDENTIAL

Not all the ADHD kids have hyperactivity symptoms ! (People easily misunderstand this as the only symptom) (大眾容易誤認為過度活躍是唯一徵狀) Inattention is always missed out ! 專注力不足往往不容易被察覺而被怱略! CONFIDENTIAL

ADHD: Biological Basis生理基礎 Misconception that ADHD is due to bad parenting despite biological basis of the disorder ADHD常被誤解為行為問題, 或是家長管教的問題 ! 其實ADHD 大部份是生物因素形成的問題…..

Genetic Basis of ADHD基因 Evidence from: • Family studies • Adoption studies • Twin studies • Molecular genetics (identified genes include: DRD4, DAT1, DRD5, DBH, 5HT1b, C4b)

ADHD Symptom Scores are Highly Heritable 高度遺傳性 ! 所以ADHD 小朋友, 很多時候他們的家長也有ADHD ! 指數愈接近 “1”, 代表 100% 來自遺傳

Interaction between Genes and Family Environment 基因和家庭環境之相互關係 Influence of parenting on child 家庭教育對孩童的影響 Antisocial parents provide environments with harsh and inconsistent reactions which affect the child’s behaviour 激進 (反社會)的父母塑造了苛刻和非協調的環境, 從而影響了孩童的行為 Influence of children on parents 孩童對父母的影響 Children with antisocial behaviour can induce negative parenting. Stimulant therapy of child has been shown to alter parental behaviour 而有激進 (反社會) 行為的孩童會引致不良的家庭教育 ! 刺激物治療法對孩童可有效改善變父母的家庭教育行為

Neuroimaging Findings神經影像發現.. Changes in some brain areas ADHD 患者腦部的改變 Castellanos et al., 1996 Castellanos et al., 2001 Durston et al., 2005 Reduction of about 5% towards brain volume in ADHD patients ADHD 患者的腦容量會比正常人細少約5%

Aetiology: Neuroanatomy – total brain volume 在腦部發展的任何時期, 不分男女, ADHD 患者的腦容量都是比正人為小 Adapted from EINAQ ,Castellanos et al 2002 EINAQ: European Interdisciplinary Network for ADHD Quality Assurance

智障青少年多動症的生物相關因素 不管青少年的認知能力，青少年多動症的症狀與父母多動症的症狀相關 DRD4基因變異和青少年組轉移的能力與青少年多動症的症狀相關，獨立於認知功能 Reference: Neece, C.L., Baker, B.L., & Lee, S.S. (2013) ADHD among adolescents with intellectual disabilities: pre-pathway influences. Research in Developmental Disabilities, 34, 2268-2279.

Etiological Factors ADHD 的病因 CONFIDENTIAL

Etiological Factors病因 Average heritability of 0.80 - 0.85 (遺傳指數高達 0.80 – 0.85 Environmental factors are not the cause, but may contribute to the expression, severity, course, and comorbid conditions 環境因素並非病 因, 不會有機會影響病的表徵, 嚴重性, 長遠對患者的影響 Dysfunction in prefrontal lobes 腦前葉的功能失常 Involved in inhibition, executive functions 負責抑制能力及組織協調能力 Genes involved in dopamine regulation 基因因素 Dopamine transporter (DAT1) gene implicated 7 repeat of dopamine receptor gene (DRD4) implicated Gene x environment interactions Possible differences in size of brain structures腦結構大小的差別 Prefrontal cortex, Corpus callosum, caudate nucleus Abnormal brain activation during attention & inhibition tasks 在需要專注力或處理抑制行為, 出現不正常的腦部活動 CONFIDENTIAL

Brain Structure & Function 腦部結構和功能 Differences in brain maturation, structure, function (particularly abnormalities in frontostriatal circuitry): Prefrontal cortex Basal ganglia Cerebellum These areas of the brain are associated with executive function abilities: Attention, spatial working memory, and short-term memory Response inhibition and set shifting 腦部不同部份負責不同工作…………….. CONFIDENTIAL

Neurotransmitters 神經傳遞物質 Neurotransmitter differences, particularly in levels of:神經接收器的落差 Dopamine多巴胺 Norepinephrine 正腎上腺素 Epinephrine腎上腺素 Serotonin血清素 Dopamine has been associated with approach and pleasure-seeking behaviors 多巴胺常被介定為: 與親近別人及尋求歡樂的行為有關 Norepinephrine plays a role in emotional/behavioral regulation 正腎上腺素能影響情緒和行為的控制 多巴胺是相當重要神經傳遞物質……. ADHD 患者的多巴胺水平就是不足, 因而出現各種專注力 & 過店活躍 / 衝動行為 CONFIDENTIAL

Executive Functioning Deficits 執行功能的缺少 Cognitive processes which activate, integrate, and manage other brain functions 認知過程能影響其它腦部功能 Examples:例子: Cognitive: working memory, planning, use of organizational strategies 認知能力:工作記憶、計劃、組織策略 Language: verbal fluency, communication 語言能力:語言流暢度、溝通 Motor: response inhibition, motor coordination 反應能力:抑制、協調 Emotional: self-regulation of emotion, frustration tolerance 情感能力:情緒自制 Controversial issues:爭議點: EF deficits overlap with ADHD symptoms 執行功能的缺少與ADHD徵狀同時出現 EF deficits are not unique to ADHD 執行功能的缺少不是ADHD獨有的 Not all children with ADHD have EF deficits不是所有患上ADHD的孩童都 有執行功能的缺少 CONFIDENTIAL

A Possible Developmental Pathway for ADHD (ADHD 發病圖) 基因危基 懷孕時受酒精、煙草或其它影響 多巴胺傳遞受干擾 正面腦葉及腦部基底核不正常 不能正常地作出抑制 出現認知缺憾於記憶力、語言能力和自我控制力 出現專注力不足、過度活躍和衝動行為徵狀 通常ADHD被發現的時候, 巳經是較遲的階段 出現社交和學業發展的缺失 家庭教育 (養育) 被干擾 出現對抗性反叛和品格障疑的徵狀 From Mash & Wolfe, 2007 CONFIDENTIAL

ADHD: Prevalence and Demographics 發病率和人口分佈性 Overall prevalence 3% to 10% in school-aged children internationally 國際性資料顯示, 3%至10%適齡學童會患上此病 Diagnosed in boys 3 to 4 times more often than in girls 男孩患者比女孩患者高3至4倍 Persists in 30% to 50% of patients into adolescence and adulthood (symptom profile may change) 30%至50%患者會持續患病至青少年和成年期 The wide variation in prevalence can be explained by the lack of a strict definition for the disorder, lack of precise and objective methods for assessment, geographic differences, and low awareness of the disorder. Sex ratios also vary widely and may, in part, be explained by referral bias. Males are more likely than females to have behaviour and conduct problems and thus more likely to be referred for psychiatric follow-up1. ADHD persists in some patients into adolescence and adulthood, however the core symptoms change. With increasing age the core symptoms of hyperactivity/impulsivity tend to decrease, although inattention persists. 1. Barkley RA. Attention-Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment. New York: Guilford Press, 1988.

Commodities that ADHD kids suffer ADHD會引致甚麼後果？ CONFIDENTIAL

Defining Comorbidity 複病症 (同時有其他病症) 定義 ADHD is highly comorbid ADHD 是高度複病症性 (很容易會同時有其他病症) Comorbidity is defined as two different diagnoses present in an individual patient 複病症性是指兩種不同診斷的病症出現於同一個病人 It is important to recognize comorbid disorders 了解複病症的問題很重要 Comorbidities may require treatment independent from and different to therapy for ADHD 複病症性可能需要獨立和有別於ADHD診療的治療 Studies of children with attention deficit hyperactivity disorder (ADHD) consistently document high rates of comorbid psychiatric conditions, including conduct disorders, anxiety disorders, depression and other mood disorders, to name a few1,2. Comorbidity is defined as two different diagnoses present in an individual patient. It is important to recognise comorbid disorders. Comorbidities may require treatment independent from and additional to therapy for ADHD. 1. Brown TE. Attention deficit disorders on comorbidities in children, adolescents and adults. Washington DC: American Psychiatric Press Inc, 2000. 2. Barkley RA. Attention-Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment. New York: Guilford Press, 1988.

Associated Problems相關問題 Peer problems 同輩問題 Inattentive symptoms  ignored專注力不足徵狀被怱略 Hyperactive/impulsive symptoms  actively rejected 過度活躍/衝動徵狀被否定 Not deficient in social reasoning/understanding, but rather the execution of appropriate social behavior 並非社交認知不足,而是不能做出適當的社交行為 Family dysfunction/parental issues家庭方面 No clear causal relationship between family problems and ADHD 家庭問題和ADHD並無清晰關係 Family problems can impact the severity and developmental course/outcomes of ADHD 家庭問題能影響ADHD的發展和嚴重性 Self-esteem自尊心 Inflated: Positive illusory bias (Hoza) 自尊心過高:正面偏見 Low self esteem associated with comorbid depression自尊心 低落:抑鬱症複病症 CONFIDENTIAL

Co-occurring Disorders in Children (n=579)於孩童出現的多種病症 Oppositional Defiant Disorder 40% 只有ADHD Tics 11% 手腳震動 ADHD alone 31% 對抗性反判 Conduct Disorder 14% Anxiety Disorder 34% Given the high rate of comorbidity with ADHD, a differential diagnosis must exclude coexisting conditions that are symptomatically distinct (e.g. conduct disorder, learning disability, oppositional defiant disorder, Tourette’s disorder, and speech or language disability)1 and require distinct management. 1. Zametkin AJ, Ernst M. Problems in the management of attention-deficit hyperactivity disorder. N Engl J Med 1999; 340: 40-46. 品格障礙 焦慮症 MTA Cooperative Group. Arch Gen Psychiatry 1999; 56:1088–1096 Mood Disorders 4% 情緒障礙

ADHD: Comorbid Conditions複症狀 60 40 20 (%) Oppositional defiant Anxiety Learning Mood Conduct disorder Smoking SUD Tics 焦慮症 學習 吸煙 手腳震動 情緒 自殺 對抗性反判 品格障礙 Milberger et al. Am J Psychiatry 1995:152:1793–1799 Biederman et al. J Am Acad Child Adolesc Psychiatry 1997;36:21–29 Castellanos. Arch Gen Psychiatry 1999;56:337–338 Goldman et al. JAMA 1998;279:1100–1107 Szatmari et al. J Child Psychol Psychiatry 1989;30:219–230

艱辛的道路 嬰兒/幼童階段 0-3 歲 容易煩躁 睡眠不安 不服從 學前階段 3-6 歲 很快便轉換遊戲 身體活動停不下來 社交困難 小學階段 6-12歲 容易分心 衝動及破壞性的行為 學習及社交困難 自信心低 　 學前階段 3-6 歲 很快便轉換遊戲 身體活動停不下來 社交困難 Notes: The mentioned signs are suggested by the opinion of clinical experts and might be understood merely as risk factors rather than as diagnostic signs.

青少年階段 13-17歲 成人階段 18歲以上 學習困難 人際關係的問題 難以計劃事情 侵略/攻擊性行為 對抗性行為 濫用藥物/酒精 冒險行為 成人階段 人生欠缺目標 自尊心低落 人際關係的問題 情緒病 睡眠問題 18歲以上 忽略健康 衝動性行為 濫用藥物/酒精 危險駕駛 財政困難 Notes: Substance abuse onset earlier, last longer and remit more slowly

ADHD 延醫的後果 對兒童的影響 過度活躍 被家人斥責 同輩排斥 ADHD 衝動 常常做出危險行為和錯誤決定 自尊心低落 情緒困擾 專注力弱 成績不理想

ADHD 延醫的後果 對家庭的影響 夫婦因管教問題爭執 夫婦出現感情問題 ADHD兒童的負面行為 父母常要責備子女 親子關係疏離 家庭關係差 失去互信基礎 常被老師、親友設訴子女的不良行為 父母承受多方面厭力

我們應如何處理ADHD?

家長對ADHD治療的迷思 阿仔啲行為真係好似ADHD ，但係都係觀察多一陣先決定醫唔醫…可能過一年半載無事呢… 我帶個仔去睇醫生，咪即係承認佢有病! 俾人睇到佢食藥，會歧視我個仔… 我個仔咁細就叫佢食藥， 會唔會好多副作用架…會唔會食到鈍左架…大左又會唔會身體唔好… 聽講有個音樂治療班，唔知會唔會好過食藥呢? Highlights the myths of public towards ADHD If they can concentrate on TV game, they must not have ADHD. Truth- even for people with ADHD, they can still concentrate on something that they like e.g. fishing, TV They oppose with intention Truth- they just cannot follow instruction and not listen to others because of their inattention but not their intention, however some ADHD children develop into ODD (Oppositional Defiant Disorder) if ADHD cannot be detected at the earlier stage 3. It must be related to the parenting skills Truth- the cause is unknown but parenting is not the cause for it. It is an indirect factor for the severity of symptoms. If parents learn effective parenting skills, child’s problem may improve 4. Boys are always like that Truth – Boy: girl = 6:1 clinic referrals Boy: girl = 1:1 in adult clinic (Brown, 2005) Biederman et al.(2005): clinical correlates of ADHD are not influenced by gender and that gender differences reported in groups of subjects seen in clinical settings may be caused by referral biases. Underdiagnose of women in childhood because they did not bring trouble

ADHD 治療 藥物治療 行為治療 認知行為治療 感覺統合治療 社交訓練

Behavioural treatment MED + Behavioural treatment EFFICACY OF INTERVENTIONS Symptomatic normalisation rates in the MTA study Educational intent: to represent just one example of many of the relative effectiveness of interventions   SPEAKERS’ NOTES The Multimodal Treatment study of children with ADHD (MTA study) is the single most important randomised clinical trial of treatment strategies for ADHD. 579 combined-type children, aged 7-9.9 years, were assigned to 14 months of: MED – medication management (titration followed by monthly visits) IBT – intensive behavioural treatment (parent, school and child components) MED+IBT – the two combined, or Community care – standard community care (treatment by community providers). All four groups showed sizable reductions in symptoms over time, but there were significant differences among them in the degree of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioural treatment or community care. In direct comparisons, combined and medication management treatments did not differ significantly, but in several instances (oppositional/ aggressive symptoms, internalising symptoms, teacher-rated social skills, parent-child relations and reading achievement), combined treatment proved superior to intensive behavioural treatment and/ or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two-thirds of community-treated subjects received medication during the study period. Swanson et al 2001 analysed the clinical relevance of these primary findings by calculating success rates based on severity of ADHD and ODD symptoms at the end of treatment. End-of-treatment status was summarised by averaging both parent and teacher ratings of ADHD and ODD symptoms on the Swanson, Nolan, and Pelham version IV (SNAP-IV) scale and low symptom severity (‘just a little’) on this continuous measure was established as the clinical cut-off point for ‘successful treatment’. This success rate analysis confirmed a large effect for the MTA medication algorithm but a slightly superior effect for multimodal treatment (p<0.05). It showed that: one-third of patients have their ADHD and ODD symptoms successfully treated by intensive behavioural treatment sophisticated medical management is superior to CBT multimodal treatment is slightly superior to medical management. 藥物治療是必須的 (因為是腦部問題), 配合行為治療是較有效處理ADHD的方案,效果更理想 Community treatment Behavioural treatment MED MED + Behavioural treatment 社區治療 行為治療 藥物治療 藥物及行為治療 Swanson et al 2001

NICE Guidelines (UK) Methylphenidate為第一線的 ADHD 藥物 CONFIDENTIAL

鹽酸甲酯 (Methylphenidate) 藥物 藥效 一般鹽酸甲酯 4-8小時 (每日服2-3次) 長效釋放劑型鹽酸甲酯 12小時 (每日1次) 作為第一線藥物治療 ADHD 1 長效藥可改善 : 1 小朋友忘記服藥的問題 避免孩子因經常於同學面前服藥而感到自卑和尷尬 避免孩子因常服藥而覺得麻煩反感，同時父母不用常常督促服藥，照顧相對輕鬆 小朋友能與家長建立更好的關係 1.) ADHD - NICE Guideline 2008 (National Institute for Health and Care Excellence)

Releasing Profile

Full active day treatment coverage offers a number of benefits1 Develops both academic & social competencies Reduces risk of accidents Improves role functioning in and out of school Promotes overall wellbeing and resilience Limited impact on sleep Improves family relationships Full active day treatment offers a number of benefits that promote overall wellbeing and resistance. Improves social and academic functioning, which may promote normal development of personality and social and academic competencies.1,2 Sleep may be less impaired with full active day treatment, avoiding doses later in the evening.1 Buitelaar and Medori Eur Child Adolesc Psychiatry 2010;19(4):325-40 Banaschewski et al. Eur Child Adolesc Psychiatry 2006;15(8):476-95 Take home message... Full active day treatment offers a number of benefits 1. Buitelaar and Medori Eur Child Adolesc Psychiatry 2010;19(4):325-40

Safety Profile In two open-label, long-term safety trials (N=1514, up to 27 months): treatment discontinuation rate was low at 6.7%. adverse event profile was similar to that observed in shorter term trials. Effects of prolonged therapy with Concerta on growth are clinically insignificant.

非刺激中樞神經藥物 部份患者可能需要服食一些非刺激中樞神經藥物，例如；托莫西汀(Atomoxetine) 非一線藥物 小朋友的表現亦可有改善。這類藥物一般適用於對刺激中樞神經藥物無效的患者。 1 1.) ADHD - NICE Guideline 2008 (National Institute for Health and Care Excellence)

一項隨機、雙盲、安慰劑對照研究，包括113名兒童和38名青少年 擇思達® 在12週內持續改善 ADHDRS總分 一項隨機、雙盲、安慰劑對照研究，包括113名兒童和38名青少年 （ LSM 95% CI ）：由最小二乘法統計出的得分均數值。 (n = 51) 安慰劑 ADHD RS總分 （LSM 95% CI） (n = 100) 擇思達 ** * *** *** P =.013 0.5 1.2 0.48 0.55 0.72 0.82 效應值 一项随机、双盲、安慰剂对照研究纳入了151例患者，在两周后服用托莫西汀的剂量为0.5-1.2 ㎎/㎏/天。以ADHD父母评定量表第4版作为疗效评定标准。 结果证明，托莫西汀与安慰剂在疗效方面在第4周时有显著统计学差异，在第12周研究终点时，其差异达到最大。在托莫西汀组内部，第6周与第12周疗效之间亦有显著统计学差异。 研究B4Z-XM-LYDM 正如图示所阐明的，有证据显示托莫西汀治疗引起的患者症状改善在用药后的数月仍持续得到增强。 这是一项紧急进行的为期12周的双盲有安慰剂对照的随机临床试验，用以评估托莫西汀对新确诊为注意力缺陷多动症的6-15岁的儿童和青少年患者的疗效。 根据注意力缺陷多动症第四版患者父母评分标准所测量的结果：总体而言，接受托莫西汀治疗的患者在为期12周的观察期中症状持续改善，从基线水平的平均39.1分到12周时的26.3分），其注意力涣散和高反应性/冲动分量评分也有所降低。 而在安慰剂治疗组中，该评分降低的幅度却极小，从基线时的39.5分降至12周时的34.8分。 试验结束时（12周），两个治疗组之间的差异达到最大并具有临床相关性（两组之间的均值差异为7.9，P<.001)。 (From Newcorn et al. 2009 [IDEA study]: only patient characteristic predictive of achieving a much improved clinical response was being at least minimally improved by week 4. [Newcorn JH, Sutton VK, Weiss MD, Sumner CR. Clinical responses to 择思达 in attention-deficit/hyperactivity disorder: the Integrated Data Exploratory Analysis {IDEA} Study. J Am Acad Child Adolesc Psychiatry 2009;48{5}:511–518.]) *P=.001 ** P=.003 *** P <.001 劑量(㎎/㎏/天) 擇思达®療效在第4週與安慰劑出現顯著差異 研究終點時擇思达®組效應值及與安慰劑的差異均達到最大 擇思达®第12週與第6週療效具有顯著差異 Montoya et al. Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naïve children and adolescents with attention deficit/hyperactivity disorder Curr Med Res Opin 2009;25(11):2745-54. 49

13項臨床研究的薈萃分析，601例12－18歲青少年ADHD患者 擇思達® 2年間持續 有效治療青少年 13項臨床研究的薈萃分析，601例12－18歲青少年ADHD患者 40 30 20 10 療效2年間持續控制症狀，ADHD RS評分改善58%，顯著改善ADHD症狀 停藥率 療效不足：16.5% 耐受性問題:5.2% 副反應沒有觀察到具有臨床意義的身高，體重，血壓，心率以及心電圖異常 平均ADHD-RS量表總分 Meta-analysis Key points: Further evidence for the long-term efficacy of ATX has been obtained in this meta-analysis involving adolescent patients participating in one of 13 atomoxetine studies: 6 double-blind, and 7 open-label. Patients were aged 12 to 18 and had a DSM-IV diagnosis of ADHD, any subtype. The mean final dose of ATX was 1.41 mg/kg/d, and treatment took place over a period of up to 2 years. Mean ADHD RS total score showed a large and significant improvement in ADHD symptoms over the first 3 months, with symptoms remaining improved for the duration of the study without dosage escalation. Of the 601 atomoxetine-treated entering patients in this meta-analysis, only 16.5% (n = 99) discontinued treatment over the 2-year period due to lack of effectiveness. 5.2% (n = 31) discontinued due to an adverse event. Source: Wilens TE, Newcorn JH, Kratochvil CJ, Gao H, Thomason CK, Rogers AK, Feldman PD, Levine LR. Long-term atomoxetine treatment in adolescents with attention-deficit/hyperactivity disorder. J Pediatr 2006;149:112–119. Data extracted from Fig. 2, p. 115. Use SigmaPlot 10.0 file “DMB.Data.Wilens.LTAdolesc.TmwsEffic-OC_All.jnb” from original manuscript folders. P value is from figure legend in manuscript. Dose is in the paper on p. 115, column 2, Para. 3, line 4. 月 0 3 6 9 12 15 18 21 24 Wilens et al. LONG-TERM ATOMOXETINE TREATMENT IN ADOLESCENTS WITHATTENTION-DEFICIT/HYPERACTIVITY DISORDERJ Pediatr 2006;149:112–119. 50

藥物可能帶來的副作用 大都屬輕微及短暫 療程開始初期患者可能會無胃口、頭痛及失眠等情況 經醫生處理後一般都可以受到控制 Concerta Package Insert, Aug, 2009

鹽酸甲酯會引致「唔長高」嗎??? 由於鹽酸甲酯可能會導致無胃口，有家長因此擔心小朋友會「唔長高」或「唔長肉」 跟據一個ADHD 藥物研究，服用鹽酸甲酯的小朋友長大到成年後，身高並沒有明顯影響

鹽酸甲酯會引致「反應慢」嗎??? 由於鹽酸甲酯能減少多動病徵，有家長因此擔心小朋友會「反應慢」 如使用的劑量過高或兒童對鹽酸甲酯有敏感問題，部份兒童可能會有「納悶」的情況出現 經醫生調較劑量後一般都可以改善情況

總結及建議 每15位小朋友便有1人患上ADHD ，可見此病其實並不罕見 ADHD 是腦部傳遞物質Dopamine 不足夠所致, 因此並非只是行為上的問題, 所以必須正視, 及早治療 家長如懷疑孩子患上ADHD ，應及早正視並尋找專業人士協助 藥物治療及行為治療是有效處理ADHD的方案，而研究亦發現兩者合併治療可帶來更理想的效果

謝謝 ! drwongchunghin@gmail.com CONFIDENTIAL