Attention Deficit Hyperactivity Disorder Larry Gray, MD Developmental and Behavioral Pediatrics Department of Pediatrics University of Chicago Pritzker School of Medicine

Copyright Alcohol Medical Scholars Program Introduction 740 % h production 25 fold h in Adderall USA = 80 % of Ritalin Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Lecture Aims Epidemiology + course Diagnosis Etiology Treatment Relationship to substance use Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Key Points Very common: 10 % of boys Poor attention + impulsivity Pharmacotherapy improves sxs Treatment protects from later SUD Copyright Alcohol Medical Scholars Program

Evolving Nomenclature Moral deficit Minimal brain disorder Autopsy studies and crude x-rays Attention Deficit Disorder (ADD) Attention Deficit/Hyperactivity D/O Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Epidemiology Very common in elementary age Estimates from: Classroom teachers = 12% Parents = 7 % Psychiatrist interview = 2% National US survey: 2003 4.4 million school age children ( ~ 6% ) Boys 2.5 X’s > girls Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Natural History Symptoms identified in school Peak prevalence: 9-12 yrs of age Symptoms lessen with age Symptoms persist > 25 yrs in 2/3 Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Lecture Aims Epidemiology + course Diagnosis Etiology Treatment Relationship to substance use Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program DSM-IV Diagnosis 1 Impairing inattentive symptoms with 6+ of: Not listening Fails to finish tasks Difficulty organizing Loses things Easily distracted Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program DSM-IV Diagnosis 2 Impulsive Blurts out answers Difficulty waiting turn Interrupts others Hyperactive Fidgets Unable to stay seated Inappropriate running Difficulty engaging in activities quietly Always “on the go” Talks excessively Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Symptom Criteria Persistent pattern > 6 months Onset < 7 years Impairments At school and home In social, academic, or occupational functioning Not due to: Conduct disorder Depression Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program ADHD Differential Normal high activity Thyroid disorders Hearing loss Sleep disorder Trauma / severe neglect Learning disabilities Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program ADHD Comorbidty ADHD 66% 33% ODD / CD 24% Anxiety/ Mood D/O Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program ADHD Subtypes Inattentive + 6/9 criteria inattention only 27 % Impulsive / hyperactive + 6/9 impulsive/hyperactive criteria only 18 % Combined + 6/9 both inattention and I/H criteria 55% Copyright Alcohol Medical Scholars Program

Presentation in Childhood 6 – 12 year olds: Too distracted Too talkative Parents describe as “immature” Often need to repeat grades Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Presentation in Teens Adolescents 12 – 18 years: Inner sense of restlessness Disorganization is 10 complaint Managing skills get overwhelmed Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program ADHD and Driving > 5X’s Speeding tickets > 3X’s Car accidents > 12X’s Moving violations > 3 X’s $ Damages Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Lecture Aims Epidemiology + course Diagnosis Etiology Treatment Relationship to substance use Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Pathophysiology Different etiologies at work No one brain mechanism → Behavioral syndrome of: Brain anatomical differences Genetic / Molecular differences Environmental risk factors Copyright Alcohol Medical Scholars Program

Environmental Influences Prenatal factors (i.e. low birth wt) Neurotoxin exposure Prenatal (i.e. alcohol) Postnatal (i.e. lead) CNS infections - encephalitis Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Genetic Influences Twin Studies Identical twins > fraternal twins Heritability estimates 7 candidate genes Dopamine D4 receptor Dopamine transporter gene (DAT 1) Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Dopamine Synapse Dopamine Transporter Dopamine Dopamine Receptor from: www.drugabuse.gov Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Lecture Aims Epidemiology + course Diagnosis Etiology Treatment Relationship to substance use Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Treatment of ADHD Effective: Behavioral Therapy Pharmacotherapy Combination of both Ineffective: Family, individual, or cognitive therapy Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Pharmacotherapy Stimulants mainstay Methylphenidate (Ritalin) D-amphetamine salts (Adderall) Less addictive potential Same structure and action as cocaine Enters brain more slowly (less reinforcing) Success =“normalized” behavior Copyright Alcohol Medical Scholars Program

Multimodal Treatment Study of Children with ADHD (MTA) ADHD alone: Success rates approach 90 % Stimulants > behavioral tx Comorbid ADHD Need medication + behavioral therapy Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program 3 Year MTA Follow-Up All kids improve Stimulants lose advantage Can meds be stopped? Copyright Alcohol Medical Scholars Program

Success or Undertreatment ? 20 % dx but no meds % 10 % dx on meds 4 Male Age 17 Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Lecture Aims Epidemiology + course Diagnosis Etiology Treatment Relationship to substance use Copyright Alcohol Medical Scholars Program

Adolescents and Substances High School seniors report 50% used alcohol 25 % used tobacco 25% “some” illicit drug use ADHD is ↑ in those with SUD 50% of adolescents 25% of adults Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program ADHD, CD and SUD ADHD 66% 33% ODD / CD 40% CD SUD Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program ADHD, CD and SUD Exp. of antisocial behavior ADHD w/o CD ≠ ↑ risk ADHD’s role in SUD Earlier onset (1 year vs 3 years) Persistence of symptoms across development Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Alcohol Use Disorders F/U 165 sons of alcoholics 6% with ADHD: no SUD 20 yrs later CD in childhood 18 X the risk of SUD CD ↑ ↑ risk of alcohol use D/Os ADHD sx assoc. much weaker Copyright Alcohol Medical Scholars Program

Predictors of Problems with Alcohol in ADHD 129 with ADHD vs. 96 no ADHD ADHD persisters w/o CD—2.5 X’s ADHD persisters with CD—5 X’s Persistence / quality of symptoms Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Treatment Effects Unmedicated = ↑ risk for SUD Use substances to ↑ self- control Meta-analysis → Tx ≠↑ SUD Emerging evidence → early Tx protects Copyright Alcohol Medical Scholars Program

Prospective Study of ADHD Rate of SUD during adolescence 75 % unmedicated developed SUD 25 % medicated developed SUD SUD in treated ADHD = non-ADHD Treating ADHD may ↓ risk for SUD Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Lecture Aims Epidemiology + course Diagnosis Etiology Treatment Relationship to substance use Copyright Alcohol Medical Scholars Program

Copyright Alcohol Medical Scholars Program Summary Very common: boys > girls Poor attention + impulsivity Pharmacotherapy improves sxs Treatment protects from SUD Copyright Alcohol Medical Scholars Program