From ABC to ADHD -...

From ABC to ADHDFrom ABC to ADHD

Eric Tridas, MD

A il 3 & 4 2009April 3 & 4, 2009The Hawai’i Branch of the

International Dyslexia Association

The Developmental WebDevelopment

al ProfileEducational & Developmental

Academic–OccupationalBehavioral–Emotional

Social Interaction

Behavioral Profile

Behavioral & Cognitive

Soc a te act oHealth

Health Medical

Environment EnvironmentalEnvironment Environmental

Developmental WebDevelopmental Web

Contributing Factors to Clinical Presentationto Clinical Presentation

Developmental Profile

PROCESSING

VISUAL

AUDITORY

TACTILE-KINESTHETICINPUT

E N LTA

NEU

S

CO

GN

ITIV

E

ATTE

NTI

ON

ENTI

AL/

SIM

U

RAT

ESHORT TERM

WORKING

LONG TERM

SEQ

U

OUTPUTORAL

WRITTENWRITTEN

Visual Perceptual Problems• IMAGINEHOWCONFUSINGITWOULDBEIFEVERYT

HINGYOUREADLOOKEDLIKETHIS!• ORI FTH EWOR DSBE GINA NDEN DI NPLAC• ORI FTH EWOR DSBE GINA NDEN DI NPLAC

ESTH ATDON’NTM AKES ENSET OY OU?• TAHW FI EHT SRETTEL EREW DESREVER, or

OUT FO ODREROUT FO ODRER• w re o n al pa

T oset aelv e g e.ge ds m c er hh d t

Language Processing

• Phonology• SemanticsSemantics• Morphology

S t• Syntax• Discourse• Metalinguistics• PragmaticsPragmatics

Tactile-kinesthetic Processing

• Impacts Fine Motor Function– Progresses in a proximal-distal fashion– Affected by:

• Sense of body position or movement• Visual spatial processingp p g• Verbal-motor integration• Motor planning • Motor sequential memoryq y• Monitoring• Tone• CoordinationCoordination

Memory

• Short Term• Active workingActive working• Long Term

Short Term Memory

• Holds information for a few seconds• Limited storage capacityLimited storage capacity • Depends on:

V l– Volume– Modality

Vi l A dit T til Ki th ti• Visual, Auditory, Tactile - Kinesthetic– Attention

Working Memory

• Intermediate duration• Holding an idea in mind while developing, g p g

elaborating, clarifying, using it– Recalling answers while thinking of the question– Complex math problems– Reading (summarizing/comparing while decoding

S l ti l hil b i h t– Selecting color while remembering what you are drawing

Working Memory

• Factors affecting it:– AttentionAttention– Rate– VolumeVolume– Automaticity of skill

Long Term Memory

• Unlimited storage capacity• Long durationLong duration• Retrieval affected by:

R l f ti l– Relevancy of stimulus– Frequency of use

St t f i ti ( lid ti )– Strategy for memorization (consolidation)

Output

• Oral– Casual– Benefits from tone, gestures, etc.

• Written– Very formal– Depends on fine motor / graphomotor

function• Motor sequences, pencil grip, spatial

organizationorganization

Fine Motor Function

• Progresses in a proximal-distal fashion• Affected by:

– Sense of body position or movement– Visual spatial processing

Verbal motor integration– Verbal-motor integration– Motor planning – Motor sequential memory– Monitoring– Tone

Coordination– Coordination

Behavioral Profile

ANXIETY

DEPRESSIONINTERNALIZING

OPPOSITIONAL-DEFIANT

ANXIETY

CONDUCTATTENTIONEXTERNALIZING

AUTISMATYPICAL

SCHIZOPHRENIA

Medical Factors

CHRONIC HEALTH PROBLEMS

ASSOCIATED HEALTH

IATROGENIC HEALTH

PROBLEMS

IATROGENIC HEALTH PROBLEMS

Environmental Factors

PARENTING PARENTS

TEMPERAMENT

STRESSORS

PEERS house

PHYSICAL FACILITY TEACHERSCURRICULUM DEMANDS

TEMPERAMENT

CURRICULUM DEMANDS

Developmental WebDevelopmental Web

Management

Educational ManagementEducational Therapy

Speech & Language Therapy

Occupational Therapy

REMEDIATION Weakness

CIRCUMVENTION StrengthsCIRCUMVENTION Strengths

Volume

Rate

Technology

Complexity

Psychological Management

ADULT FOCUSED Behavioral Therapy

CHILD FOCUSED Cognitive Therapy

Medical Management

MEDICATIONMEDICATION

SURGERY

Environmental Management

HOMEHOME

SCHOOL

DyslexiaDyslexia

Etiology

Phonological ProcessingPhonological Processing

Phonology

• Phoneme: – Building block of words

S ll t it f h– Smallest unit of speech– There are 40 - 52 phonemes in the English language – Are put together to form wordsAre put together to form words

• Words can be broken down into their elemental sounds allowing us to decipher words

• Deficits in phonology strongly correlate with reading problems

Phonologic System

• Processing and production of speech sounds

• Earliest language system to develop• It is natural does not have to be taught• It is natural – does not have to be taught• It is the foundation of language

Phonological Processing Deficits

Phonological R idPhonologicalAwareness

RapidNaming

PhonologicalMemory

Fluency

• The ability to read text– Quickly– Accurately– With good understanding

• The hallmark of a good reader• Is the bridge between decoding and g g

comprehension• It is acquired word-by-wordq y

Dyslexia Etiology

• Language problem specific to the Phonologic Module– Functional part of the brain where

• Sounds of language (phonemes) are put together to form wordstogether to form words

• Words are broken down into their elemental sounds (phonemes)

• Discriminates words from noise– Learning to read is not a natural biological

processprocess

Dyslexia: Neurobiology

S

Phoneme Processing

Speech

Visual Word - Fluency

Typical Readers Dyslexic Readers

Typical Readers: ypElision versus Repetition

left right

Eden et al., 2004

Dyslexia: Neurobiology

Control

Eden et al. Nature 1996 Dyslexic

Reading: NeurobiologyReading: NeurobiologyPhonological processing

Phoneme Processing

catcattæk

Reading: NeurobiologyReading: NeurobiologyVisual - Fluency

Visual Word - Fluency

catcat

Reading Disability

(D x F) + C = Reading

D = DecodinggF = FluencyC = Comprehensionp

M. Joshi; IDA National Conference November 2004

Reading Disability

GeneralGeneral Intelligence

Vocabulary

Text DecodingFluency

Word Identification

Reasoning

= Meaning

g

Concept Formation

Early IdentificationEarly Identification

What to look for

Early Signs of Dyslexia

• By age of onset:– Delay in speakingDelay in speaking– Difficulty in pronunciation– Insensitivity to rhymeInsensitivity to rhyme– Poor word retrieval or word finding– Naming the letters and their sounds– Naming the letters and their sounds


• Infants and toddlers– Delay in speakingDelay in speaking

• First word by 1 year• Phrases by 18 - 24 months• Parents may ascribe it to family history

– Speech delay and dyslexia are familial


• Preschool years– Difficulty in pronunciationDifficulty in pronunciation

• No “baby talk” by 5 or 6 years of age• Typical problems:

– What to listen for» Omission of initial sounds: lephant for elephant,

chi-en for chicken» Inverting sounds: aminal for animal


• Preschool years– Insensitivity to rhymeInsensitivity to rhyme

• Unable to recite nursery rhymes– Children that remember nursery rhymes tend to be

d dgood readers

• Unable to differentiate between similar and different words

– Can not focus on parts of the words» What rhymes with: food, talk


• Poor word retrieval or word finding– Talking around a word (circumlocution)Talking around a word (circumlocution)– Uses words like “stuff” or “things”


• Naming the letters and their sounds– Before entering Kindergarten

• Knows the names of upper and lower case letters

– Before entering 1st grade• Knows the names and sounds of letters• Knows the names and sounds of letters• Alphabetic principle

– Sequence of letters = number and sequence of soundsM t h b i i d f d• Matches beginning sounds of words

• Pronounces beginning sounds of words• Counts phonemes in small words


• Typical development– 4 – 6 y/o aware that words come apart4 6 y/o aware that words come apart– 6 y/o 70% can count phonemes in small words

• Early signs of dyslexia• Early signs of dyslexia– After 1 year of reading instruction (end of 1st

grade) can’t separate sounds of spoken wordgrade) can t separate sounds of spoken word

Common Signs of Dyslexia

• Problems with:– Phoneme segmentationPhoneme segmentation– Phoneme deletion– Specific word retrieval (i e tornado forSpecific word retrieval (i.e. tornado for

volcano, prostitute for prosecute)– Rapid word retrievalRapid word retrieval

History Screening: Infancy

Y N• Single words by 1 yr ■ ■Single words by 1 yr ■ ■• Phrases by 2 yrs ■ ■

F il hi t f l• Family history of language or reading problems ■ ■

History Screening: PreschoolEnd of K – 4 Y N• Omission of sounds ■ ■

– Eliminates initial sounds (i.e., lephant for elephant)

• Inverts sounds ■ ■( i l f i l)(aminal for animal)

• Insensitivity to rhyme ■ ■– Can’t memorize nursery rhymes

C ’t t ll if d h– Can’t tell if words rhyme• Does not know lower case alphabet ■ ■

History Screening: Kindergarten

By the end of year CAN NOT: Y N• Name upper and lower caseName upper and lower case

alphabet ■ ■• Name most letter sounds ■ ■Name most letter sounds ■ ■• Match beginning sounds to words ■ ■• Pronounce beginning sounds of• Pronounce beginning sounds of

words ■ ■

History Screening: 1st Grade

By the end of year CAN NOT: Y N• Can separate and / or countCan separate and / or count

sounds in a word ■ ■Fi d th i ht d• Find the right words ■ ■

Screening Test: End of 1st Grade

• Alphabetic principle P F– Names beginning letters of words ■ ■Names beginning letters of words ■ ■– Names beginning sounds of words ■ ■– Names ending letters of words ■ ■Names ending letters of words ■ ■– Names ending sounds of words ■ ■– Can tell # of sounds in a word ■ ■– Can tell # of sounds in a word ■ ■

Screening Test: K.5 and 1st Grade

• Rhyming P F– Say a word that rhymes withSay a word that rhymes with

• Food ■ ■• Walk ■ ■

– Can recite a rhyme ■ ■

History Screening: Infancy

Y N• Single words by 1 yr ■ ■Single words by 1 yr ■ ■• Phrases by 2 yrs ■ ■

F il hi t f l• Family history of language or reading problems ■ ■

History Screening: PreschoolEnd of K – 4 Y N• Omission of sounds ■ ■

Eli i t i iti l d– Eliminates initial sounds(i.e., -lephant for elephant, chi-en for chicken)

• Inverts sounds ■ ■(aminal for animal)

• Insensitivity to rhyme ■ ■– Can’t tell if words rhyme

• Does not know lower case alphabet ■ ■

History Screening: Kindergarten

By the end of year CAN NOT: Y N• Name upper and lower caseName upper and lower case

alphabet ■ ■• Name most letter sounds ■ ■Name most letter sounds ■ ■• Match beginning sounds to words ■ ■• Pronounce beginning sounds of• Pronounce beginning sounds of

words ■ ■

History Screening: 1st Grade

By the end of year CAN NOT: Y N• Can separate and / or countCan separate and / or count

sounds in a word ■ ■Fi d th i ht d• Find the right words ■ ■

Screening Test: End of 1st Grade

• Alphabetic principle P F– Reads the words accurately ○ ○Reads the words accurately– Names beginning letters of words ○ ○– Names beginning sounds of words ○ ○Names beginning sounds of words ○ ○– Names ending letters of words ○ ○– Names ending sounds of words ○ ○– Names ending sounds of words ○ ○– Can tell # of sounds in a word ○ ○

Screening Test: K.5 and 1st Grade

• Rhyming P F– Say a word that rhymes withSay a word that rhymes with

• Food ○ ○• Walk ○ ○

InterventionIntervention

What to do about it.

Research Based Reading Instruction• Essential Components

– Phonemic awareness• Recognize, remember and manipulate individual soundsg p

– Phonics and word recognition• Sound – symbol relationship, word meaning

– Reading Fluency• Read with sufficient speed an accuracy to support

comprehension – Vocabulary development

• Individual word meanings• Individual word meanings– Reading comprehension

• Verbal reasoning, background knowledge, comprehension strategiesg

Reading Instruction

• Other components– Basic writing skillsBasic writing skills

• Compose English with accuracy, fluency and clarity of expression

– Comprehending and using language• The ability to listen and understand the

i f h t i imeaning of what someone is saying

Effective Reading Instruction• Explicit

– Clearly and directly explained not left to discovery• Systematic

– The speech sounds, spelling patterns, sentence structures, text genre and language conventions

• CumulativeC ti l i kill b ild th– Continual review one skill builds on another

• Multisensory• Sequential and Incremental

M bl t– Manageable steps• Data driven

– Emphasis, speed of instruction and support are determined by student's progressstudent s progress

Dyslexia: Management

• Critical to start before 3rd grade• It is almost impossible to remediateIt is almost impossible to remediate

after 4th grade

l iEarly Intervention IS Urgent•10TH %ile 5th Grade reader

•50,000 words/year

•50TH %ile 5th grade reader•600,000 words/year

•Average students receive approximately 10 TIMES as

h ti imuch practice in a year

Anderson, Wilson & Fielding 1998

Dyslexia: Pre-testing Post-testing

yManagement

Dyslexia-specific brain activation profile becomes normal following successful remedialsuccessful remedial training

Simos, Fletcher, et al. Neurology,2002

What About Attention?What About Attention?

ADHD: What it is and what is not!What it is and what is not!

H ki ti R ti

ADHD: Historical TimelineHyperkinetic Reaction of Childhood (DSM-II)

Attention Deficit Hyperactivity Minimal Brain Damage Disorder (DSM-III-R)

1960 19801968 1987 19941930193019021902

Minimal Brain Dysfunction

1960 19801968 1987 19941930193019021902

y

Attention Deficit Disorder + or -Hyperactivity (DSM-III)

ADHD-like syndromefirst described

Attention Deficit/Hyperactivity Disorder (DSMAttention Deficit/Hyperactivity Disorder (DSM--IV)IV)

Diagnostic Criteria for ADHD: gDSM-IV• Persistent symptoms of inattention and/or impulsivity and

hyperactivity

• Onset of symptoms before age 7

• Impairment in 2 or more settings (eg, school, work, home)p g ( g, , , )

• Evidence of clinically significant impairment in social, academic, or occupational functioning, p g

• Symptoms not a result of other disorders

Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. Washington, DC: American Psychiatric Association; 2000.

DSM-IV Diagnostic Criteria gSymptoms for ADHD

• Inattention (>6)I l

– Is disorganizedA id /di lik t k– Is careless

– Has difficulty sustaining attention

– Avoids/dislikes tasks requiring sustained mental effortg

in activity– Does not listen

– Loses important items– Is easily distracted

– Does not follow through with tasks

y– Is forgetful in daily

activities


DSM-IV Diagnostic Criteria gSymptoms for ADHD (cont’d)

• Impulsivity— Blurts out answers

Cannot wait turn

• Hyperactivity (>6)– Squirms and fidgets

Cannot stay seated — Cannot wait turn— Intrudes/interrupts others

– Cannot stay seated– Runs/climbs excessively– Cannot play/work quietly– Is on the go/driven

by a motor– Talks excessively


ADHD: DSM-IV Subtypes

• ADHD Combined Type– Criteria are met for both inattention and C te a a e et o bot atte t o a d

impulsivity/hyperactivity (> 6 of each)• ADHD Inattentive Type

– Criteria met for inattention but not for impulsivity/hyperactivity (> 6)

• ADHD Hyperactive-Impulsive Type– Criteria met for impulsivity/hyperactivity but not for p y yp y

inattention(> 6)

ADHD C bid C di iADHD: Comorbid Conditions60

55

50

4540%

40

35

30

25

20

(%)

30–35%

20–25% 15–25%

15–20% 20% 19%20

15

10

5

0

15%

Oppositionaldefiantdisorder1

Anxietydisorders3

Learningdifficulties2

Mooddisorders2

Conductdisorder3

Smoking4 Substanceusedisorder5

Languagedisorder2

1MTA Cooperative Group. Arch Gen Psychiatry 1999; 56:1076–1086.2Barkley R. Attention-deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment, 2nd ed. New York: Guilford Press, 1993.3Biederman J, et al. Am J Psychiatry 1991; 148:565–577.4Milberger S, et al. J Am Acad Child Adolesc Psychiatry 1997;36:37–44.5Biederman J, et al. J Am Acad Child Adolesc Psychiatry 1997;36:21–29.

C biditI C With ADHDComorbidity Is Common With ADHDComorbidity Is Common With ADHD

ADHD

CONDUCT (10%) Oppositional

Di d (40 50%)Oppositional

ADHD Disorder (40-50%)ADHDpp

Disorder (40-50%)

AnxietyDisorderAnxietyDisorder

Conduct (10%)

(35%)MoodDisorder(5-25%)

(35%)MoodDisorder(5-25%)ADHD Only (50%)ADHD Only (50%)

EtiologyEtiology

A Variety of Functional & StructuralA Variety of Functional & StructuralA Variety of Functional & StructuralA Variety of Functional & StructuralDifferences Appear in the ADHD BrainDifferences Appear in the ADHD Brain

Normal Controls ADHD

y = +21 mm y = +21 mm1 x 10-2 1 x 10-2y = +21 mm y 21 mm1 x 10

1 x 10-3 1 x 10-3

MGH-NMR Center & Harvard- MIT CITP Reprinted by permission of Elsevier Science from Anterior cingulate

cortex dysfunction in ADHD revealed by fMRI

and the Counting

Stroop , by Bush G, Frazier JA, Rauch SL, et al.,

MGH-NMR Center & Harvard- MIT CITP Reprinted by permission of Elsevier Science from Anterior cingulate cortex dysfunction in ADHD revealed by fMRI and the Counting Stroop , by Bush G, Frazier JA,RauchSL, et al., Biological Psychiatry 45(12), Copyright 1999 by the Society of Biological Psychiatry.

Twin Studies Show ADHDTwin Studies Show ADHD Is a Genetic Disorder

HeightBreast cancer Asthma Schizophrenia

Levy, 1997Nadder, 1998

Hudziak, 2000

Gjone, 1996Silberg, 1996

Sherman, 1997y,

Edelbrock, 1992Schmitz, 1995Thapar, 1995

Willerman, 1973Goodman, 1989

Gillis, 1992

Faraone. J Am Acad Child Adolesc Psychiatry. 2000;39:1455-1457. Hemminki. Mutat Res. 2001;25:11-21.Palmer. Eur Resp J. 2001;17:696-702.

Average genetic contribution of ADHD based on twin studies0 0.2 0.4 0.6 0.8 1

ADHD Mean

Impairment Caused by ADHDImpairment Caused by ADHD

How does it present?Impact on quality of lifeImpact on quality of life

ImpairmentAcademic

Behavioral/EmotionalBehavioral/EmotionalSocialization

M di lMedical

Impairment• ADHD is a disorder of performance, not

skill• ADHD disrupts executive function• ADHD creates problems with self• ADHD creates problems with self-

regulationADHD i h lth i k• ADHD increases health risks

Impairment• ACADEMIC

– Production vs. KnowledgeProduction vs. Knowledge• BEHAVIOR - EMOTIONAL

Spacey/Over Reactive vs Defiant– Spacey/Over-Reactive vs. Defiant• SOCIALIZATION

I ti bl M li i– Insatiable vs. Malicious• MEDICAL

– Cigarette smoking, Car accidents, SUD

ADHD: Impairment over time

Academiclimitations

RelationshipsOccupational/vocational

ADHD Low self-esteem

Legaldifficulties

Smoking andInjuriesMotor vehicle

accidentsSmoking and

substance abuse

ADHD: Impact on FamilyParents of children with ADHD experience higher levels of:

• Stress• Self-blameSelf blame• Social isolation• Depression• Depression• Marital discord

Mash and Johnston. J Clin Child Psychol. 1990;19:313.Murphy and Barkley. Am J Orthopsychiatry. 1996;66:93.

ADHD : AdultsADHD : Adults Performance Limitations• Despite similar educational levels and IQ

scores, non-medicated adults with ADHD display:– Significantly more academic difficulty in school

(25% repeat a grade)

– Lower levels of occupational advancement

Faraone S, et al. Biol Psychiatry. 2000;48:9-20.Biederman, et al. Am J Psychiatry. 1993;150:1792-1798.

ADHD Affects Socialization• Children are stigmatized by their behavior

– Disruptive behavior• Troublemakers

–Immaturity and impulsivenessCenter of attention• Troublemakers

• Bad sportsmanship• Excessive talking• Cannot sit still

U f d t i t th

•Center of attention•Breaks the rules•Blurting out answers

•Peer rejection• Unfocused, not responsive to others• Impulsive aggression

• Adolescents continue to demonstrate social problems

• Poor participation in group activities• Few friends

AACAP. J Am Acad Child Adolesc Psychiatry. 1997;36:85S-121S.Barkley RA. J Am Acad Child Adolesc Psychiatry. 1991;30:752-761.

• Vulnerable to antisocial groups, drug abuse

Increased Traffic Violations and Motor Vehicle A id i Ad l d Ad l i hAccidents in Adolescents and Adults with ADHD

7080

90ADHD n=25 Control n=23P=0.004 P=0.07

506070

ects

(%) P=0.07

P=0.01

203040

subj

e

01020

Traffic Speeding Drunk License Driver-causedTraffic violations

Speeding violations

Drunk driving

License suspended

Driver-caused accidents

Barkley RA, et al. Pediatrics. 1996;98:1089-1095.

Increased Smoking with ADHDAdult patients with ADHD

50% 48.5%

40 8%

mok

ers

30%

40%

ADHDG l

40.8%

29% n=71

urre

nt s

m

20%

30%

*P<0.01

General population

25.8%

Cu

10%

Pomerleau, et al. J Subst Abuse. 1995;7:373-378.

*Smokers Quit ratio0%

Earlier Initiation of Smoking with ADHDSmoking with ADHD

0.6

0.5

lity ADHD n=128

C t l 1096- to 17-year-old boys0.4

0.3g pr

obab

il Control n=109

0.2

0 1

Smok

ing

0.1

00 2 4 6 8 10 12 14 16 18 20 22 24

P<0.003Milberger S, et al. J Am Acad Child Adolesc Psychol. 1997;36:37-44.

Age

Untreated ADHD Is Associated WithUntreated ADHD Is Associated With Higher Risk of Substance Abuse

P=0.001use

(%)

use

(%)

P 0.001

P=0.001 P=0.001

subs

tanc

e

stan

ce a

bu

hist

ory

of s

nce

of s

ubs

Life

time

h

Prev

alen

Biederman J, et al. Biol Psychiatry. 1998;44:269-273.Biederman J, et al. Pediatrics. 1999;104:e20-e25.

Adolescent & Adult Outcome• Symptoms Persist in 50-65%• Associated Problems

– Conduct– EmotionalEmotional– Socialization– Education– Education– Employment

Satisfactory Outcome in 60 70%• Satisfactory Outcome in 60-70%

Management of ADHDManagement of ADHD

Good Management of ADHDgInvolves MultimodalTherapy

Multimodal Therapy

MedicationMedication Psychosocial TherapyPsychosocial TherapyStimulantsStimulants Parent TrainingParent TrainingAntidepressantsAntidepressants Child-Focused Treatment Child-Focused Treatment Alternatives SNRI’s School-Based InterventionSchool-Based Intervention

Normalization in Many AreasNormalization in Many Areas

MTA St d Obj ti d D iMTA Study Objective and DesignMTA Study Objective and DesignMTA Study Objective and Design

Objective:Objective:•• To compare the long-term efficacy ofTo compare the long-term efficacy of pharmacotherapy, behavioral

therapy, and combination therapy in the treatment of ADHD therapy, and combination therapy in the treatment of ADHD Protocol:Protocol:•• Population: 579 children with ADHD combined type, aged 7-9.9 yearsPopulation: 579 children with ADHD combined type, aged 7-9.9 years•• In a 4-group parallel design, children randomly assigned to:In a 4-group parallel design, children randomly assigned to:

–– Medication alone (primarily methylphenidate)Medication alone (primarily methylphenidate)–– Behavioral therapy aloneBehavioral therapy alone–– Combination of medication and behavioral treatmentCombination of medication and behavioral treatment–– Routine community care (medication and behavioral treatment)Routine community care (medication and behavioral treatment)

•• Duration of study treatment: 14 monthsDuration of study treatment: 14 months

The MTA Cooperative Group. Arch Gen Psychiatry. 1999;56:1073-1086.

MTA Study: Treatment Outcome: yTeacher-Rated InattentionCC3

3314-Month Outcomes14-Month Outcomes

Teacher-rated Inattention (MTA Group, 1999)Teacher-rated Inattention (MTA Group, 1999)2.52.5

Community Control22

´´

Behavior Modification

Medical Management11

1.51.5 ´

Combination TherapyComb, Med Mgt > Beh, CC

00

0.50.5

The MTA Cooperative Group. Arch Gen Psychiatry. 1999;56:1073-1086.

Assessment Point (Days)Assessment Point (Days)00

100100

200200

300300

400400

00

Long-term Outcomes of Therapies forLong term Outcomes of Therapies for ADHD in the MTA Study

Hyperactive Impulsive Symptoms(Teacher Reports)

70

(%)

65 60%

40

50

60

14 m

onth

s (

55

45

56%60%

45%

36%

20

30

40

vem

ent a

t 1 35

25

15

36%

0

10

Medication Combination Behavioral Community based

Impr

ov 15

5

Medicationmanagement

Combinationtherapy

Behavioraltreatment

Community-basedtreatment

The Developmental WebDevelopmental Profile

Educational & Developmental

Academic – OccupationalBehavioral – Emotional

Social Interaction

Behavioral Profile

Behavioral & Cognitive

Health

Health Medical

Environment EnvironmentalEnvironment Environmental

American Academy of Pediatrics: G id li f th T t t f ADHDGuidelines for the Treatment of ADHD

• Establish a treatment program that recognizes ADHD as a chronic condition

• Specify appropriate target outcomes to guide management• Prescribe stimulant medication and/or behavior therapy to• Prescribe stimulant medication and/or behavior therapy to

improve target outcomes in children with ADHD• If the treatment program has not met target outcomes,

evaluate:– Original diagnosis– Use of all appropriate treatments– Adherence to the treatment plan

Presence of coexisting conditions– Presence of coexisting conditions• Using information from parents, teachers, and the child,

follow-up to evaluate target outcomes and adverse effects

AAP. Pediatrics. 2001;108:1033-1044.

Types of Medications Used InTypes of Medications Used In Managing ADHD

ADHD

STIMULANTS SNRI’s

Amphetamines Atomoxetinemethylphenidate

dextroamphetamine Mixed AmphetaminesImmediate Release

PulseOROS

Transdermal

d-methylphenidate

Immediate ReleaseImmediate Release

PulseImmediate Release

Pulse

Immediate ReleasePulse

lisdexamfetamine

Dopamine

Norepinephrine

R t kReuptake pumps

Medication

Receptors

Proposed Effect of Stimulants

Increase Dopamine Production

AmphetaminesAmphetamines

MethylphenidateAtomoxetine

Decreases Dopamine ReuptakeDecreases Dopamine Reuptake

Medications: Clinical Impact• Increase control of attention• Increase impulse controlIncrease impulse control• Decrease activity

D di ti b h i• Decrease disruptive behavior• Improve handwriting (in 50%)

Medications: Clinical Impact• Academic • Increase Production

• Behavior • Increase ComplianceDecrease Disruption

• Socialization

Decrease Disruption

• Increase Awareness

Stimulant Medications• Side Effects

– Insomnia (50-60%)– Anorexia (50-60%)– Irritability (30%)– Headache– Stomachache– Nausea– Tics

Atomoxetine: Side Effects

• Anorexia• Dizziness - SleepinessDizziness Sleepiness• Dyspepsia

D titi• Dermatitis• Constipation• Mood Swings• Transient elevation of liver enzymesTransient elevation of liver enzymes• Increased suicidality

Medications: Duration of Action

• Short Acting: 4 hours• Intermediate Acting: 6 – 8 hoursIntermediate Acting: 6 8 hours• Long Acting: 8 – 12 hours

24 h24 hours

Medications• Short-Acting • Ritalin, Dexedrine, DextroStat,

Focalin Methylin (Tablet, Chewable & Liquid)

• Intermediate-Acting • Ritalin SR, Metadate ER, Adderall, Ritalin LA, Metadate-CD Methylin ER Focalin XR

• Long-Acting

CD, Methylin ER, Focalin XR

• Dexedrine Spansules, Cylert, Adderall-XR Concerta

• 24 hours

Adderall-XR, Concerta, Daytrana, Vyvanse

• Strattera

®MPH OROS (Concerta®)tr

atio

n m

L)

IR MPH 10 mg tid (n=15)CONCERTA® 36 mg qd (n=15)

12

16

20

Con

cent

(ng/

m

4

8

Time (h)0 2 4 6 8 10 12

0

MedicineCompartment

#1

MedicineCompartment

#2

PushCompartment

MedicineCompartment

#1Outer Coat of Medicine

MPH SODAS™ (Ritalin® LA)MPH SODAS (Ritalin LA)Pulse Release

SODAS™ is a trademark of Elan Corporation, Plc

Pulse Delivery System (SODASPulse Delivery System (SODAS, Difucaps)

15

20

entra

tion

0

5

10

Con

ce

20 4 6 8 10 12 14 160

Time (h)

Mixed Amphetamine SaltsMixed Amphetamine Salts (Adderall XR® )Formulation Study

® ®

25

30Adderall® 10 mg BID

Adderall XR® 20 mg QD

Bioequivalence of Adderall XR® 20 mg QD to Adderall® 10 mg BID

ne

20

25Dextroamphetamine

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etam

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10

15

D-a

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5LevoamphetamineM

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Tulloch et al. Pharmacotherapy 2002;22:1405.

0 4 8 12 16 20 24 28 32 36 40 44 48 52Time (h)

Daytrana DOT Matrix™y OTransdermal Technology

• Methylphenidate is mixed with adhesive

DOT Matrix is a trademark of Noven Pharmaceuticals, Inc.

Pharmacokinetics with DaytranaC f

50

10 mg Daytrana 20 mg Daytrana 30 mg Daytrana

Mean Plasma Concentration of d-methylphenidate

Mean Plasma d-MPH Conc

30

40

50

d MPH Conc (ng/mL)

0

10

20

0 1 2 3 4 5 6 7 8 9 10 11 12Time post-dose (hr)

Patch Patch d

Lower limit of quantification 0.25 ng/mL.

Pierce et al. Poster presented at the AACAP Annual Meeting. Toronto. October 20, 2005.

applied removed

Application and Removal/Disposal

• Holding the patch down, the rest of the liner should be removed slowly and theremoved slowly and the exposed half should be pressed against the skinTh h h ld b d• The patch should be pressed down with the palm of the hand for 30 seconds

• Upon removal, the patch should be folded in half, with sticky sides together, and y g ,discarded immediately in toilet or lidded container

™Vyvanse™

• Is a pro-drug – Inactive until the body breaks it downInactive until the body breaks it down

• Combines an amphetamine and an amino acidamino acid– Dextroamphetamine and lysine

It lasts12+ hrs• It lasts12+ hrs• Not affected by GI transit time or pH

Atomoxetine (Strattera™) o o e e (S e )Efficacy

Behavioral ManagementBehavioral Management

What to do at Home

Core Principles for Behavior pManagement

• Immediacy of Consequences• Frequency of Consequences• Saliency of Consequences• Frequent Changes in Rewards

A t D ’t Y k• Act, Don’t Yack• Positives Before Negatives• Anticipate ProblemsAnticipate Problems• Pick Your Fights - Prioritize• Expect Variabilityp y• Practice Forgiveness

It is not your faultIt is not your fault…

But it is your problem

From ABC to ADHD -...

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