The Diagnosis and Treatment of ADHD

1. The Diagnosis and Treatment of ADHD Jess P. Shatkin, MD, MPH Vice Chair for Education NYU Child Study Center New York University School of Medicine

2. Learning Objectives Residents will be able to: • Identify symptom criteria for ADHD. • State the major rule-out diagnoses. • Identify the primary comorbidities. • Describe the diagnostic process. • Choose between various treatment options based upon their risk/benefit profiles.

3. The Story of Fidgety Phillip--Dr. Heinrich Hoffman, 1844

4. "Let me see if Philip can Be a little gentleman; Let me see if he is able To sit still for once at table." Thus spoke, in earnest tone, The father to his son; And the mother looked very grave To see Philip so misbehave. But Philip he did not mind His father who was so kind. He wriggled And giggled, And then, I declare, Swung backward and forward And tilted his chair, Just like any rocking horse;- "Philip! I am getting cross!"

5. History of ADHD • Minimal Brain Dysfunction (damage): 1900 – 1950 • Hyperkinetic/Hyperactivity Syndrome (DSM-II of 1968): 1950 – 1969 • Recognition of Attentional impairment and Impulsivity: 1970 – 1979 • Diagnostic Criteria (DSM-III) and “ADD” with or without Hyperactivity: 1980 • ADD becomes ADHD (DSM-IIIR) w/mixed criteria: 1987 • ADHD (inattentive, hyperactive, combined subtypes) in DSM-IV: 1994

6. Differential Diagnosis(Psychiatric) • Mood and/or Psychotic Disorder • Anxiety Disorder • Learning Disorder • Mental Retardation/Borderline IQ • ODD/Conduct Disorder • Pervasive Developmental Disorder • Substance Abuse • Axis II Disorders • Psychosocial Cx (e.g., abuse, parenting, etc.)

7. Differential Diagnosis(Medical) • Seizure Disorder (e.g., Absence, Complex-Partial) • Chronic Otitis Media • Hyperthyroidism • Sleep Apnea • Drug-Induced Inattentional Syndrome • Head Injury • Hepatic Illness • Toxic Exposure (e.g., lead) • Narcolepsy

8. DSM-IV Diagnostic Criteria(Inattention) • Makes careless mistakes/poor attention to detail • Difficulty sustaining attention in tasks/play • Does not seem to listen when spoken to directly • Difficulty following instructions • Difficulty organizing tasks/activities • Avoids tasks requiring sustained mental effort • Loses items necessary for tasks/activities • Easily distracted by extraneous stimuli • Often forgetful in daily activities

9. DSM-IV Diagnostic Criteria(Hyperactive/Impulsive) • Fidgets • Leaves seat • Runs or climbs excessively (or restlessness) • Difficulty engaging in leisure activities quietly • “On the go” or “driven by a motor” • Talks excessively • Blurts out answers before question is completed • Difficulty waiting turn • Interrupts or intrudes on others

10. DSM-IV Functional Criteria • 6 of 9 symptoms in either or both categories • Code as: Inattentive; Hyperactive-Impulsive; or Combined Type • Persisting for at least 6 months • Some symptoms present before 7 y/o • Impairment in 2 or more settings • Social/academic/occupational impairment

11. Epidemiology (1) • Most commonly diagnosed behavioral disorder of childhood (1 in 20 worldwide) • 3 – 7% of school children are affected in U.S. • Males:Females = 2 – 9:1 • Virtually all neurodevelopmental disorders are more common in boys prior to age 10 years; by adulthood, we get closer to 1:1 ratios

12. Epidemiology (2): Gender Paradox • Girls typically show less hyperactivity, fewer conduct problems, & less externalizing behavior • Yet we see a gender paradox • The group with the lower prevalence will show a more severe clinical presentation, along with severity/greater levels of comorbidity (Loeber & Keenan, 1994) • Consistent with multifactorial/polygenic conditions: • The idea is that it takes a greater accumulation of vulnerability and risk factors to put an individual from the lower-afflicted group “over the top”

14. Epidemiology (3) • At least 30 – 50% maintain diagnosis for ≥ 15 yr • Strongest predictor of poor prognosis is pre-pubertal aggression • Over 80% of psychotropics are Rx by PCPs: stimulants (>50%), antidepressants (30%), mood stabilizers (13%), anxiolytics (7%), & antipsychotics (7%) • ADHD related outpatient visits to PCPs increased from 1.6 – 4.2 million between 1990 - 93

15. Too Much of a Good Thing? • Between 1991 – 2000, the annual production of MPH rose by 740%; production of amphetamine increased 25x during this same period. • In 2000, America used 80% of the world’s stimulants; most other industrialized countries use 1/10 the amount we do. Canada uses stimulants at 50% of the US rate. • Rates vary by states and regions: Hawaii has the lowest per capita MPH use by a factor of 5. “Hot spots” are mostly in the east near college campuses and clinics that specialize in Dx/Rx.

16. But wait, there’s more! • Approximately 2.5 million children in the US (ages 4 – 17) took medication for ADHD in 2004 • Sales of medications used to treat ADHD rose to $3.1 billion in 2004 from $759 million in 2000

17. Medical Expenditure Panel Survey, 2008 3.5% of US children (2.8 million kids) aged 18 and younger received a stimulant medication in 2008, up from 2.9% in 1996 Stimulant use in girls increased over 10 years from 1.1% to 1.6% Stimulant use in preschoolers decreased, stayed the same for 6 – 12 y/o, and increased for adolescents

18. Hey, Kids Can’t Have All the Fun! • Adult use of these medications increased 90% between March 2002 and June 2005…can you say Strattera?! • Use of meds to treat ADHD in adults aged 20 – 44 rose 19% in 2005 • An estimated 1.7 million adults aged 20 – 64 and 3.3 million children under 19 took medication for ADHD in 2005 • Use increased 2% for those 10 – 19 • Use decreased by 5% for those under 10

19. ADHD is Familial • Family studies: (1) sibling risk increases 2-5x; (2) 3-5x increased likelihood that parent is affected (9 – 35%)

20. Symptom Evolution Inattention Hyperactivity Impulsivity Time

21. —Age— ADHD: Course of the Disorder Inattention Hyperactivity Impulsivity

22. Why More ADHD? • Improved recognition by physicians? • Increase in prevalence? • An easing of standards for making the diagnosis? • An easing of standards for prescribing medication?...or the “Prozac” connection? • Increased scholastic demands? • Changing parental habits? • Managed care and the pharmaceutical industry? • 1991 amendments to IDEA?

23. Potential Areas of Impairment Academic limitations Children Relationships Occupational/ vocational Adults ADHD Low self esteem Legal difficulties Motor vehicle accidents Injuries Smoking and substance abuse Adolescents

24. Comorbidities (1) • 2/3 of children with ADHD present with ≥ 1 comorbid Axis I disorder:

25. Comorbidities (2) • ≥ 84% of children with ADHD demonstrate psychopathology as adults • Adolescents w/ADHD Rx w/stimulants have lower rates of substance abuse than untreated adolescents w/ADHD • Educational impairments • Employment problems • Greater sexual-reproductive risks • Greater motor vehicle risks

29. Natural History • Rule of “thirds”: • 1/3  complete resolution • 1/3  continued inattn, some impulsivity • 1/3  early ODD/CD, poor academic achievement, substance abuse, antisocial adults • Age related changes: • Preschool (3-5 y/o) – hyperactive/impulsive • School age (6-12 y/o) – combination symptoms • Adolescence (13-18 y/o) – more inattn w/restlessness • Adult (18+) – largely inattn w/periodic impulsivity

30. Neuroimaging

31. Brain Imaging and ADHD • Numerous imaging studies have now demonstrated the following: • The caudate nucleus and globus pallidus (striatum) which contain a high density of DA receptors are smaller in ADHD than in control groups • ADHD groups have smaller posterior brain regions (e.g.,occipital lobes) • Areas involved in coordinating activities of multiple brain regions are (e.g., rostrum and splenium of corpus collosum and cerebellar vermis) are smaller in ADHD

32. Developmental Trajectories of Brain Volume Abnormalities in Youth with ADHD • Smaller brain volumes in all regions regardless of medication status (cortical white & gray matter) • Smaller total cerebral (-3.2%) and cerebellar (-3.5%) volumes • Volumetric abnormalities (except caudate) persist with age • No gender differences • Volumetric findings correlate with severity of ADHD • Castellanos et al, 2002

33. Cortical Thickness in ADHD: Cingulate Cortex Makris et al. Cerebral Cortex 2006 Shaw et al., Arch Gen Psychiatry 2006

34. Specific Genes Associated w/ADHD • Rare mutations in the human thyroid receptor β gene on chromosome 3 • Symptoms suggestive of ADHD are found among those w/a general resistance to thyroid hormone (Hauser et al, NEJM, 1993) • Dopamine Transporter gene (DAT) on chromosome 5 • A “hyperactive” presynaptic DAT (Gill et al, Mol Psych, 1997) • Dopamine Receptor D4 gene (DRD4) on chromosome 11 • Postsynaptic malfunction do not allow signal transmission (Swanson et al, Mol Psych, 1998)

38. Cortical Thickness & DRD4Shaw et al.AGP 2007

39. Potential Non-Genetic Causes • Non-genetic causes of ADHD are also neurobiological in nature • Perinatal stress • Low birth weight • Traumatic brain injury • Maternal smoking during pregnancy • Severe early deprivation (extreme) • Nigg, 2006

40. Executive Functioning • Most children with ADHD have impairments in executive functioning, including: • Response inhibition • Vigilance • Working memory • Difficulties with planning • Wilcutt et al, 2005

41. Neuropsychological Testing • Nigg (2005) in a meta-analysis identified the most common abnormalities in various neuropsych tasks in ADHD (listed by Effect Size): • Spatial working memory (0.75) • CPT d-prime (0.72) • Stroop Naming Speed (0.69) • Stop Task Response Suppression (0.61) • Full Scale IQ (0.61) • Mazes, a planning measure (0.58) • Trails B Time (0.55)

42. Establishing a Convincing Diagnosis (1) • There is no single test to identify ADHD • Available “tests” are primarily Continuous Performance Tests (CPTs): • TOVA (Test of Variables of Attention) • Conner’s CPT • Gordon Computerized Diagnostic System • I.V.A. CPT • Diagnosis must be multi-factorial

43. Establishing a Convincing Diagnosis (2) • Clinical Interview: • Diagnostic Assessment of Primary Complaint • Review of Psychiatric Systems (e.g., attention, hyperactivity/impulsivity, oppositional & conduct difficulties, mood, anxiety, psychosis, trauma, neurovegetative systems, tics, substance abuse, etc.) • Medical, Psychiatric, & Developmental History • Detailed Educational History • Detailed Family & Social History

44. Establishing a Convincing Diagnosis (3) • Collateral interviews: • Patient • Primary Caregivers (parents, grandparents, etc.) • Teachers • School Counselors • Sunday School Teachers • Coaches • Music Teachers • Camp Counselors (e.g., Boys & Girls’ Club)

45. Establishing a Convincing Diagnosis (4) • “Some” symptoms by age 7 years • This criterion has been maintained in 3 versions of the DSM, despite a lack of empirical support • Likely leads to increased false-negatives • DSV-IV field trials demonstrated that inattentive subtype exhibited a later onset (Applegate et al, 1997) • An adult population survey found that only 50% of individuals with clinical features of ADHD retrospectively reported symptoms by age 7, but 95% reported symptoms before age 12 & 99% before 16 (Kessler et al, 2005) • DSM-V will possibly reset age to 12 years to decrease rate of false negatives (Kieling et al, 2010)

46. Establishing a Convincing Diagnosis (5) • Symptoms in ≥ 1 setting: • Never diagnose ADHD in a 1:1 interview • Individuals with ADHD can often function well in certain settings with no signs of symptoms when they are interested and maintain total focus (e.g., playing Nintendo, watching videos, etc.) • Symptoms in group settings are a must!

47. Establishing a Convincing Diagnosis (6) • Rating scales: • SNAP – IV (for parents & teachers) • Conners (for teachers, parents, and affected adults) • ACTeRS (for teachers & parents) • Child Behavior Checklist • Behavior Assessment System for Children (BASC) • ADHD Rating Scale – IV • Brown ADD Scales

50. Establishing a Convincing Diagnosis (7) • Treatment trial: • Risk of adverse effects is significant • Not necessarily “diagnostic” even if effective • At least 2 – 3 medications should be attempted before patient deemed non-responder • Very low placebo response with treatment of ADHD