1. ATTENTION- DEFICIT/HYPERACTIVITY DISORDER Puja Patel PGY5 Pediatric Neurology Nov 6, 2013

2. Epidemiology  Overall prevalence 2-18%  School age children 8-10%  most common neurobehavioral disorder of childhood  More common in boys than girls  Male to female ratios: 4:1 for predominantly hyperactive type 2:1 for predominantly inattentive type

3. Clinical Features 2 categories of core symptoms:  Hyperactive and impulsive behaviors occur together  Inability to sit still or inhibit behavior  Observed by age 4, peaks age 7-8, then hyperactive symptoms decline but impulsive symptoms persist  Inattention  Reduced ability to focus attention, reduced speed of cognitive processing and responding  Apparent at 8-9 years old, usually lifelong

4. Diagnostic Criteria DSM-5  Age <17 years: ≥6 symptoms in 1 or both categories  Age ≥17 years, ≥5 symptoms of in 1 or both categories  Present > 1 setting  Persist > 6mo  Present before age 12  Inconsistent with developmental level child  Impair functioning  Exclude psychiatric disorders

5. DSM-4 vs DSM-5  New overall diagnostic category  Neurodevelopmental disorders (DSM-5) vs Disorders usually first diagnosed in infancy, childhood and adolescence (DSM-4)  ADHD across lifespan  Not only a disorder of childhood  Adding new examples to apply criteria across lifespan  Lower age cutoff for diagnosis in adults  Age of onset changed from 7 to 12  Removal of PDD/ASD from exclusion criteria  Allows for diagnosis of ADHD with comorbid PDD/ASD

6. Changes from subtypes to presentations: DSM-4 vs DSM-5  Combined subtype  Inattention + hyperactive-impulsivity  Predominantly inattentive type  Predominantly hyperactive-impulsive type  Combined presentation  Predominantly inattentive  6 inattentive and 3-5 hyperactive/impulsive symptoms  Inattentive (restrictive)  6 inattentive and no more than 2 hyperactive/impulsive symptoms  Predominantly hyperactive/impulsive DSM-4DSM-5

7. Prevalence distribution of DSM-4 subtypes

8. Etiologies Genetic factors account for ~80% of etiology  Twin studies demonstrate concordance as high as 92% in monozygotic twins and 33% in dizygotic twins  5-6x higher risk of first degree relatives affected  Genes that may play a role:  DA and serotonin-Rs and transporters  DA beta-hyroxylase  Glutamate-R

9. Etiologies Mixed reviews on environmental factors:  Maternal factors  Smoking, prenatal alcohol, lead, viral infections  Perinatal/early life risk factors  Premature infants with BW<1500gm  Striatum and cingulate-cortical loop vulnerable to ischemia induced release of glutamate  Post-natal risk factors  Cerebral trauma/infections, thyroid dysfunction, toxins, nutritional deficiencies  Genetic factor likely basic cause; environmental factor probably secondary, acting as a trigger

10. Comorbid disorders  Primary vs secondary  ADHD subtype specific comorbidities Prevalence of comorbid disorders for children with ADHD vs those without Larson et al, 2007

11. Evaluation  Keep in mind diagnostic criteria for ADHD  Evaluate medical/neurologic/developmental disorders  Hearing/visual impairment, genetic/metabolic, sleep d/o, seizures, med effects, learning disabilities, language d/o  FHx similar behaviors  Evaluate for emotional/social stressors  Screen for psychiatric conditions  Substance abuse in adolescents

12. Evaluation  Behavior rating scales to be completed > 2 informants  ADHD specific (narrow-band): focus directly on core symptoms Sensitivity and specificity>90% Conners and the ADHD Rating Scale IV for preschoolers Vanderbilt for children ≥4 years  Broadband scales: Assess variety of behavioral symptoms Less sensitive and specific Can help identify coexisting conditions  Educational evaluation mandated by schools in US  Core symptoms in classroom  Neuropsych testing (IQ and academic) to eval learning d/o

13. Treatment  Preschool children (4-5yo)  Behavior therapy administered by parent or teacher  Addition of medication (stimulant) if fails behavioral therapy  School age children (6-11yo) and adolescents (12- 18yo)  Medication + behavioral therapy  Treat coexisting conditions concurrently with ADHD

14. Behavior therapy  Modifications in physical and social environment using rewards and nonpunitive consequences  Positive reinforcement, time-out, token economy  Small reachable goals  Keep organized: maintaining daily schedule, charts/checklists  Keep on task: minimum distractions, limiting choices  School based interventions  Qualifications for special ed/IEP/accommodations under section 504  Tutoring/resource room support  Classroom modifications  Extended time to complete tasks

15. Pharmacologic Treatments Stimulants first line  Methylphenidate (Ritalin), dexmethylphenidate (focalin), amphetamine (adderall)  NE and DA reuptake inhibitor/releasing agent  Advantages: rapid onset of action, safe, long and short-acting forms approved in children<6  SEs: appetite suppression, retard growth trajectory, insomnia, mood lability, rebound, tics, psychosis, abuse potential, sudden cardiac death (rare)

16. Pharmacologic Treatments Non-stimulants  Atomoxetine (straterra)  NE reuptake inhibitor  Adv: no abuse potential  Disadv: less effective than stimulants, decrease dose if use with P450 inhibitors  SEs: somnolence, GI symptoms, decreased appetite, SI (rare), hepatitis (rare)  Alpha-2 adrenergic agonists (not FDA approved)  Guanfacine (tenex), clonidine (catapres)  Adv: no abuse potential, helpful if coexisting sleep or tic disorders  Disadv: less effective than stimulants  SEs: somnolence, dry mouth, hypotension, orthostasis

17. Treatment considerations  Monitor treatment response  Drug holidays not routinely recommended  Consider if aberrant growth trajectory, excessive SEs  Stopping medications  Consider if stable symptoms  Time appropriately  Stimulant medications and atomoxetine do not need taper  Taper alpha-2-adrenergic agonists

18. Prognosis 30-60% continue to manifest appreciable symptoms into adult life  Impaired academic functioning  especially for inattentive or combined types  Some data suggests decreased rate of employment, lower job status and poor job performance  Increased risk for incurring intentional or unintentional injury  Increased risk for antisocial personality disorder in adulthood

19. References  Dalsgaard S. Attention-deficit/hyperactivity disorder (ADHD). Eur Child Adolesc Psychiatry. 2013 Feb;22 Suppl 1:S43-8  Daughton JM, Kratochvil CJ. Review of ADHD pharmocotherapies: advantages, disadvantages, and clinical pearls. J Am Acad Child Adolesc Psychiatry 2009;48(3):240-8  Klein RG et al. Clinical and functional outcome of childhood attention- deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry 2012;69(12):1295-303  Larson K et al. Patterns of Comorbidity, Functioning, and Service Use for US children with ADHD, 2007. Pediatrics 2011; 127(3):462-70  Millichap JG. Etiological Classification of Attention-Deficit/Hyperactivity Disorder. Pediatrics 2008;121(2): 358-65  Wolraich M et al. ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics 2011 Nov;128(5):1007-22  UpToDate, “ADHD in children and adolescents,” 2013  Clinical Features and Evaluation; Epidemiology and Pathogenesis; Overview of treatment and Prognosis; Treatment with Medications