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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
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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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Lecture AimsLecture Aims
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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Lecture AimsLecture Aims
Epidemiology + courseEpidemiology + courseDiagnosisDiagnosis EtiologyEtiology TreatmentTreatment Relationship to substance useRelationship to substance use
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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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Lecture AimsLecture Aims
Epidemiology + courseEpidemiology + courseDiagnosisDiagnosisEtiologyEtiology TreatmentTreatment Relationship to substance useRelationship to substance use
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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?
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% dx on meds
% dx but no meds
Male AgeMale Age
%%
44 171700
2020
1010
Success or Undertreatment ?Success or Undertreatment ?
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Lecture AimsLecture Aims
Epidemiology + courseEpidemiology + courseDiagnosisDiagnosisEtiologyEtiologyTreatmentTreatment Relationship to substance useRelationship to substance use
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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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Lecture AimsLecture Aims
Epidemiology + courseEpidemiology + courseDiagnosisDiagnosisEtiologyEtiologyTreatmentTreatmentRelationship to substance useRelationship to substance use
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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