attention deficit hyperactivity disorder larry gray, md developmental and behavioral pediatrics...

Attention Deficit Attention Deficit Hyperactivity DisorderHyperactivity Disorder

Larry Gray, MDLarry Gray, MDDevelopmental and Behavioral PediatricsDevelopmental and Behavioral Pediatrics

Department of PediatricsDepartment of Pediatrics

University of Chicago University of Chicago

Pritzker School of MedicinePritzker School of Medicine

Copyright Alcohol Medical ScholaCopyright Alcohol Medical Scholars Programrs Program

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IntroductionIntroduction

740 % 740 % production production

25 fold 25 fold in Adderall in Adderall

USA = 80 % of RitalinUSA = 80 % of Ritalin


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Lecture AimsLecture Aims

Epidemiology + courseEpidemiology + course DiagnosisDiagnosis EtiologyEtiology TreatmentTreatment Relationship to substance useRelationship to substance use


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Key PointsKey Points

Very common: 10 % of boysVery common: 10 % of boys

PPoor attention + impulsivityoor attention + impulsivity

Pharmacotherapy improves sxsPharmacotherapy improves sxs

Treatment protects from later SUDTreatment protects from later SUD


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Evolving NomenclatureEvolving Nomenclature

Moral deficitMoral deficit Minimal brain disorder Minimal brain disorder

– Autopsy studies and crude x-raysAutopsy studies and crude x-rays

Attention Deficit Disorder (ADD)Attention Deficit Disorder (ADD) Attention Deficit/Hyperactivity D/OAttention Deficit/Hyperactivity D/O


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EpidemiologyEpidemiology Very common in elementary ageVery common in elementary age Estimates from: Estimates from:

– Classroom teachers = 12%Classroom teachers = 12%– Parents = 7 %Parents = 7 %– Psychiatrist interview = 2%Psychiatrist interview = 2%

National US survey: 2003National US survey: 2003– 4.4 million school age children ( ~ 6% )4.4 million school age children ( ~ 6% )– Boys 2.5 X’s > girls Boys 2.5 X’s > girls


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Natural HistoryNatural History

Symptoms identified in schoolSymptoms identified in school

Peak prevalence: 9-12 yrs of agePeak prevalence: 9-12 yrs of age

Symptoms lessen with ageSymptoms lessen with age

Symptoms persist > 25 yrs in 2/3Symptoms persist > 25 yrs in 2/3


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Epidemiology + courseEpidemiology + course DiagnosisDiagnosis EtiologyEtiology TreatmentTreatment Relationship to substance useRelationship to substance use


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DSM-IV Diagnosis 1DSM-IV Diagnosis 1 Impairing inattentive symptoms with 6+ of: Impairing inattentive symptoms with 6+ of:

- Not listeningNot listening

- Fails to finish tasksFails to finish tasks

- Difficulty organizingDifficulty organizing

- Loses thingsLoses things

- Easily distractedEasily distracted


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DSM-IV Diagnosis 2DSM-IV Diagnosis 2 ImpulsiveImpulsive

- Blurts out answers

- Difficulty waiting turn

- Interrupts others

HyperactiveHyperactive- Fidgets

- Unable to stay seated

- Inappropriate running

- Difficulty engaging in

activities quietly

- Always “on the go”

- Talks excessively


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Symptom CriteriaSymptom Criteria Persistent pattern > 6 months Onset < 7 yearsOnset < 7 years ImpairmentsImpairments

– At school and homeAt school and home– In social, academic, or occupational functioning In social, academic, or occupational functioning

Not due to:Not due to:– Conduct disorderConduct disorder– DepressionDepression


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ADHD DifferentialADHD Differential Normal high activityNormal high activity Thyroid disordersThyroid disorders Hearing lossHearing loss Sleep disorderSleep disorder Trauma / severe neglect Trauma / severe neglect Learning disabilities Learning disabilities


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ADHD ComorbidtyADHD Comorbidty

ODD / CDODD / CD

ADHDADHD

66%66%

Anxiety/ Mood D/OAnxiety/ Mood D/O

33% 33%

24%24%


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ADHD SubtypesADHD Subtypes Inattentive Inattentive

– + 6/9 criteria inattention only+ 6/9 criteria inattention only– 27 % 27 %

Impulsive / hyperactive Impulsive / hyperactive – + 6/9 impulsive/hyperactive criteria only+ 6/9 impulsive/hyperactive criteria only– 18 % 18 %

Combined Combined – + 6/9 both inattention and I/H criteria+ 6/9 both inattention and I/H criteria– 55%55%


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Presentation in ChildhoodPresentation in Childhood

6 – 12 year olds:6 – 12 year olds:

Too distractedToo distracted

Too talkativeToo talkative

Parents describe as “immature” Parents describe as “immature”

Often need to repeat gradesOften need to repeat grades


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Presentation in TeensPresentation in Teens

Adolescents 12 – 18 years: Adolescents 12 – 18 years:

Inner sense of restlessnessInner sense of restlessness

Disorganization is 1Disorganization is 10 0 complaintcomplaint

Managing skills get overwhelmedManaging skills get overwhelmed


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ADHD and DrivingADHD and Driving

> 5X’s Speeding tickets > 5X’s Speeding tickets

> 3X’s Car accidents> 3X’s Car accidents

> 12X’s Moving violations> 12X’s Moving violations

> 3 X’s $ Damages> 3 X’s $ Damages


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Epidemiology + courseEpidemiology + courseDiagnosisDiagnosis EtiologyEtiology TreatmentTreatment Relationship to substance useRelationship to substance use


1919

PathophysiologyPathophysiology

Different etiologies at workDifferent etiologies at work No one brain mechanismNo one brain mechanism → → BBehavioral syndrome of: ehavioral syndrome of:

– Brain anatomical differences Brain anatomical differences

– Genetic / Molecular differencesGenetic / Molecular differences

– Environmental risk factorsEnvironmental risk factors


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Environmental InfluencesEnvironmental Influences

Prenatal factors Prenatal factors (i.e. low birth wt)(i.e. low birth wt)

Neurotoxin exposure Neurotoxin exposure Prenatal (i.e. alcohol)Prenatal (i.e. alcohol)

Postnatal (i.e. lead)Postnatal (i.e. lead)

CNS infections - encephalitisCNS infections - encephalitis


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Genetic InfluencesGenetic Influences

Twin StudiesTwin Studies– Identical twins > fraternal twinsIdentical twins > fraternal twins

– Heritability estimates Heritability estimates

7 candidate genes7 candidate genes– Dopamine D4 receptorDopamine D4 receptor

– Dopamine transporter gene (DAT 1)Dopamine transporter gene (DAT 1)


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Dopamine SynapseDopamine Synapse

DopamineDopamine

Dopamine Dopamine TransporterTransporter

Dopamine Dopamine ReceptorReceptor

from: www.drugabuse.govfrom: www.drugabuse.gov


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Epidemiology + courseEpidemiology + courseDiagnosisDiagnosisEtiologyEtiology TreatmentTreatment Relationship to substance useRelationship to substance use


2424

Treatment of ADHDTreatment of ADHD

Effective:Effective:– Behavioral TherapyBehavioral Therapy

– PharmacotherapyPharmacotherapy

– Combination of bothCombination of both

Ineffective:Ineffective:– Family, individual, or cognitive therapyFamily, individual, or cognitive therapy


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PharmacotherapyPharmacotherapy Stimulants mainstayStimulants mainstay

– Methylphenidate (Ritalin)Methylphenidate (Ritalin)– D-amphetamine salts (Adderall)D-amphetamine salts (Adderall)

Less addictive potentialLess addictive potential– Same structure and action as cocaineSame structure and action as cocaine– Enters brain more slowly (less reinforcing)Enters brain more slowly (less reinforcing)

Success =“normalized” behaviorSuccess =“normalized” behavior


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Multimodal Treatment Study of Multimodal Treatment Study of Children with ADHD (MTA)Children with ADHD (MTA)

ADHD alone: ADHD alone: – Success rates approach 90 %Success rates approach 90 %

– Stimulants > behavioral tx Stimulants > behavioral tx

Comorbid ADHDComorbid ADHD– Need medication + behavioral therapyNeed medication + behavioral therapy


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3 Year MTA Follow-Up3 Year MTA Follow-Up

All kids improve All kids improve

Stimulants lose advantage Stimulants lose advantage

Can meds be stopped?Can meds be stopped?


2828

% dx on meds

% dx but no meds

Male AgeMale Age

%%

44 171700

2020

1010

Success or Undertreatment ?Success or Undertreatment ?


2929


Epidemiology + courseEpidemiology + courseDiagnosisDiagnosisEtiologyEtiologyTreatmentTreatment Relationship to substance useRelationship to substance use


3030

Adolescents and SubstancesAdolescents and Substances

High School seniors reportHigh School seniors report– 50% used alcohol50% used alcohol– 25 % used tobacco 25 % used tobacco – 25% “some” illicit drug use25% “some” illicit drug use

ADHD is ADHD is ↑↑ in those with SUD in those with SUD– 50% of adolescents 50% of adolescents – 25% of adults 25% of adults


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ADHD, CD and SUDADHD, CD and SUD

ODD / CDODD / CD

ADHDADHD

66%66%33% 33%

CD SUDCD SUD

40%40%


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ADHD, CD and SUDADHD, CD and SUD

Exp. of antisocial behaviorExp. of antisocial behavior

ADHD w/o CD ADHD w/o CD ≠ ↑ risk ≠ ↑ risk

ADHD’s role in SUDADHD’s role in SUD– Earlier onset (1 year vs 3 years)Earlier onset (1 year vs 3 years)

– Persistence of symptoms across developmentPersistence of symptoms across development


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Alcohol Use DisordersAlcohol Use Disorders

F/U 165 sons of alcoholicsF/U 165 sons of alcoholics–6% with ADHD: no SUD 20 yrs later6% with ADHD: no SUD 20 yrs later

–CD in childhood 18 X the risk of SUDCD in childhood 18 X the risk of SUD

CD CD ↑ ↑ risk of alcohol use D/Os↑ ↑ risk of alcohol use D/Os ADHD sx assoc. much weakerADHD sx assoc. much weaker


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Predictors of Problems with Predictors of Problems with Alcohol in ADHDAlcohol in ADHD

129 with ADHD vs. 96 no ADHD129 with ADHD vs. 96 no ADHD

ADHD persisters w/o CD—2.5 X’sADHD persisters w/o CD—2.5 X’s

ADHD persisters with CD—5 X’sADHD persisters with CD—5 X’s

Persistence / quality of symptomsPersistence / quality of symptoms


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Treatment EffectsTreatment Effects

Unmedicated = ↑ risk for SUDUnmedicated = ↑ risk for SUD

Use substances to ↑ self- control Use substances to ↑ self- control

Meta-analysis → Tx ≠↑ SUDMeta-analysis → Tx ≠↑ SUD

Emerging evidence → early Tx Emerging evidence → early Tx

protectsprotects


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Prospective Study of ADHDProspective Study of ADHD

Rate of SUD during adolescenceRate of SUD during adolescence

75 % unmedicated developed SUD75 % unmedicated developed SUD

25 % medicated developed SUD25 % medicated developed SUD

SUD in treated ADHD = non-ADHD SUD in treated ADHD = non-ADHD

Treating ADHD may Treating ADHD may ↓ risk for SUD↓ risk for SUD


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Epidemiology + courseEpidemiology + courseDiagnosisDiagnosisEtiologyEtiologyTreatmentTreatmentRelationship to substance useRelationship to substance use


3838

SummarySummary

Very common: boys > girlsVery common: boys > girls

PPoor attention + impulsivityoor attention + impulsivity

Pharmacotherapy improves sxsPharmacotherapy improves sxs

Treatment protects from SUDTreatment protects from SUD

attention deficit hyperactivity disorder larry gray, md developmental and behavioral pediatrics...

Documents

xs car accidents

xs speeding tickets

yearsimpairmentsat school

brain anat

yrs of agesymptoms

criteria inattention

school age children

h production25 fold