黃宗顯醫生

Report
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
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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
Impulsivity
衝動行為
過度活躍
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
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
Open-minded
Excitable
Energetic
Fun to be with
持開放態度
時常都興奮
充滿活力
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
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 !
不是每個 ADHD孩童都有過度活躍徵狀 !
(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)
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
From Mash & Wolfe, 2007
出現對抗性反叛和品格障疑的徵狀
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
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
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
只有
ADHD
Oppositional
ADHD
alone
Defiant
Tics
Disorder
11%
40%
31%
Anxiety
Conduct
Disorder
Disorder
34%
14%
MTA Cooperative
Group. Arch
Mood Disorders 4%
情緒障礙
Gen Psychiatry 1999;
56:1088–1096
ADHD: Comorbid Conditions複症狀
60
(%) 40
20
0
Oppositional Anxiety
defiant
Learning
Mood
Conduct Smoking
學習
情緒
disorder
焦慮症
對抗性
反判
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
品格障礙
吸煙
SUD
自殺
Tics
手腳震
動
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
小學階段 6-12歲
 容易分心
學前階段 3-6 歲
 衝動及破壞性的行為
 很快便轉換遊戲
 身體活動停不下來
 社交困難
 學習及社交困難
 自信心低
青少年階段 13-17歲




學習困難
 對抗性行為
人際關係的問題  濫用藥物/酒精
難以計劃事情
 冒險行為
侵略/攻擊性行為
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
ADHD 延醫的後果
對兒童的影響
過度活躍
ADHD
被家人斥責
同輩排斥
衝動
常常做出危險行
為和錯誤決定
專注力弱
成績不理想
自尊心低落
情緒困擾
ADHD 延醫的後果
對家庭的影響
夫婦因管教問
題爭執
ADHD兒童
的負面行為
夫婦出現感情
問題
父母常要責備
子女
親子關係疏離
常被老師、親
友設訴子女的
不良行為
父母承受多方
面厭力
家庭關係差
失去互信基礎
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?
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
41
EFFICACY OF INTERVENTIONS
Symptomatic normalisation rates
in the MTA study
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
Normalisation rate (%)
80
68
70
56
60
50
40
34
25
30
20
10
0
Community
treatment
社區治療
Swanson et al 2001
Behavioura
l treatment
行為治療
MED
藥物治療
MED +
Behavioural
treatment
藥物及行為治療
NICE Guidelines (UK)
ADHD患者須接受包含藥物、心理、行為及教育等全面治療
Methylphenidate為第一線的
ADHD 藥物
CONFIDENTIAL
鹽酸甲酯 (Methylphenidate)
藥物
一般鹽酸甲酯
藥效
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
Promotes
overall
wellbeing
and
resilience
Limited impact
on sleep
1. Buitelaar and Medori Eur Child Adolesc Psychiatry 2010;19(4):325-40
Improves role
functioning in
and out of
school
Improves family
relationships
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)
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
ADHD RS總分
(LSM 95% CI)
( LSM 95% CI ):由最小二乘法統計出的得分均數值。
(n = 51)
安慰劑
**
(n = 100)
擇思達
*
***
***
P =.013
0.5
1.2
0.48
*P=.001 ** P=.003 *** P <.001
0.55
0.72
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.
0.82
效應值
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
平均ADHD-RS量表總分
40
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
30
停藥率
20
療效不足:16.5%
耐受性問題:5.2%
10
0
月
0
3
6
9
12
15
18
21
24
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
Wilens et al. LONG-TERM ATOMOXETINE TREATMENT IN ADOLESCENTS WITHATTENTIONDEFICIT/HYPERACTIVITY DISORDERJ Pediatr 2006;149:112–119.
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可引致不少家庭和學業上的問題,對孩子的成長和家
人關係都會造成長遠的不良影響
• 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
54
謝謝 !
[email protected]
CONFIDENTIAL

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