Recognition and Treatment of ADHD in Primary Care Settings. Disclosure 11/6/2013. Objectives

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1 Southern California Permanente Medical Group Pediatric Symposium Hyatt, Long Beach CA. 11/1/13 Recognition and Treatment of ADHD in Primary Care Settings Martin T. Stein, M.D. Professor of Pediatrics Division of Academic General Pediatrics, Child Development and Community Health University of California San Diego Rady Children s Hospital San Diego Disclosure I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider of commercial services discussed in this CME activity. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation. Objectives Participant will learn the several ADHD RX strategies to maximize effectiveness: Rating scales and teacher narratives AAP ADHD Toolkit and book for parents DSM 5: what s new for ADHD Co-existing conditions: key to accurate diagnosis Monitoring target behaviors Stimulants/non-stimulants: management strategies/ses Natural history of ADHD ADHD: preschool, adolescents and developental disabilities ADHD in primary care: making it work Non-responders to treatment 1

2 Getting the diagnosis right Interview parents and child and/or ADHD specific behavioral checklist Vanderbilt Assessment Scale Teacher narrative or behavior checklist Tell me about Joey in class about his behavior and learning style Screen for mental health disease and LD Knowledge about the family Vanderbilt Parent Rating Scale: Screening for ADHD and Co-exiting behaviors [Likert Scale: never/occasionally/often/v. often] Question: #1-9: Inattentive symptoms #10-18: Hyperactive/Impulsive symptoms #19-38: Oppositional behaviors/ Conduct Disorder #39-41: Anxiety symptoms #41-45: Depression symptoms Caring for Children with ADHD: A Resource TOOLKIT for Clinicians Vanderbilt Assessment Scale: rating scales plus achievement and classroom behavior scales Parent and teacher follow-up scales Medication and side-effects Target goals/behaviors School and home daily behavior report card Parent education hand-outs: Behavior management, appetite/weight on meds, homework tips Educational Rights of children with ADHD Working w/ your child s school ADHD in primary care TOOLKIT: productdetail&key=9c520b53-045d-4920-bc63-a88faec8ca7f 2

3 ADHD: Co-existing Conditions Oppositional Defiant Disorder 25% Anxiety Disorder 15-20% Conduct Disorder 10% Depressive Disorder 5-10% Learning disorders 20-30% OCD, PTSD, Tourette s Syndrome Environmental stressors ADHD and Learning Disabilities 4419 full-term births ( ) Follow-up min. 5yrs (to 19 yo) All medical and educational records available for review A population birth cohort from Rochester MN Incidence of ADHD: 7.2% Reading LD: 13.1% Written language LD: 15.7% Math LD: 15.5% Harris MN et al. Pediatrics DOI: /peds

4 Medications for ADHD: A History # FDA Approval RCT s #Amphetamine 1950s ******* #Methylphenidate 1960 ******* #Atomoxetine 2003 ** #Lysdexamfetamine 2007 * #Guanfacine ER 2009 * #Clonidine ER 2010 * Tricyclics * Bubroprion * [* Relative # RCT s] Case #1: ADHD Simplex 8 yo male with ADHD/C w/o Learning Disability, co-existing mental health condition or major psychosocial/family problems Stimulant Medication Methylphenidate and Amphetamines (Regulation of dopamine) Equivalent head-to-head responses in reducing core symptoms of ADHD >200 RCT s of stimulants 70% of children respond to 1 stimulant Half who fail 1 st stimulant or who have intolerable side effects, respond to 2 nd stimulant Short-acting, intermediate-acting and extended release preparations 4

5 Titrating Stimulant Medications Not weight dependent Begin low and titrate upward Variability in dose response Initial positive response may not be optimal dose to improve function Goal: optimal effects with minimal SE s Schedule depends on target outcomes (5 or 7 days/week; holidays; afternoon dose) Wender, EH. Managing Stimulant Medication for Attention Deficit/ Hyperactivity Disorder. Pediatrics in Review. (2001) 22: Choosing medication: methylphenidate Concerta Focalin XR Metadate CD Ritalin LA Duration 12 hrs hrs 1/2 dose 8 hrs 8 hrs Dosing Once Once Once (BID) Once (BID) Onset IR 22% IR bead IR bead IR 50% Ease of use Large capsule Capsule Sprinkle Sprinkle Choosing Medication: amphetamine Adderall XR Adderall Dexedrine Spansules Duration hrs 6-8 hrs 6 hrs Dosing Once BID BID Abuse Risk Medium High High Onset Slower at lower dose Ease of use Sprinkle Grind Sprinkle 5

6 Methylphenidate ER Patch Evenly dispersed, concentrated drug cells within adhesive layer Concentration gradient between drug and skin allows efficient diffusion Precise content ratios control rate of delivery Patch size conversion to MPH dose delivered over 9 hours: 12.5 cm 2 = 10 mg cm 2 = 15 mg 25 cm 2 = 20 mg 37.5 cm 2 = 30 mg Shire Inc.---the only available MPH transdermal patch Drug/Adhesive Mix Release Liner Backing Atomoxetine: Strattera 2 nd line ADHD medication Inhibitor of presynaptic norepinephrine transporter (SNRI) Non-stimulant medication Treatment failure or intolerable side effects with stimulant Substance abuse potential for stimulant Co-existing anxiety disorder Significant sleep disturbance Tic disorder Parent against use of a stimulant Michelson D et.al Pediatrics 1089:5, e83. Titrating Atomoxetine Starting dose: 0.5 mg/kg/day (3-5 days) Increase to mg/kg/day Side effects similar to stimulants Fatigue and nausea: less w/ evening dosing Single daily dose or BID May take 3-6 weeks to have detectable effects 6

7 Lisdexamfetamine Vyvanse Objective for development of drug: reduce the potential for abuse Inactive prodrug in which d-amphetamine is bound to l-lysine (inactive) Converted in GI track to the active form of d-amphetamine by cleaving lysine 30 mg, 50 mg and 70 mg produced functional improvements comparable to 10 mg, 20 mg and 30 mg of mixed amphetamine salts. Biederman J et. al. Clin Ther. 2007;29: Guanfacine: alpha 2-agonist Short acting: used off-label in ADHD (often with a stimulant) when significant disruptive behaviors or tics New extended release form: Intuniv (FDA approval for ADHD: 2009) 345 patients (6-17 yo: M=10.5 yo) with ADHD randomized to the extended-release guanfacine (2, 3, or 4 mg/day) or a placebo. Similar improvement c/w stimulants in hyperactivity and impulsivity but not inattention. Children had better response than adolescents Side effects: fatigue, sedation, minimal decr. BP and pulse Biederman J. Pediatrics Jan :e73-e84 Clonidine: alpha 2-agonist Extended-release tablets 0.1-mg and 0.2-mg (Kapvay) Treatment of ADHD (6-17 yo) FDA approval Oct for monotherapy or w/ stimulant 2 RCTs: mg BID (max. 0.4 mg) 7

8 MTA Study Multimodal Treatment Study of Children w/adhd Study of long term (14 mo.) treatment for ADHD 6 sites/579 children ages 7-9 Randomly assigned groups Medication management (methlyphenidate) Behavior treatment Combined (medication and behavior) Standard community care Jensen P et al. Arch Gen Psychiatry (1999) 56: MTA Study Multimodal Treatment Study of Children w/adhd Combined treatment did not yield significantly greater benefits than medicationonly management for core ADHD symptoms Combined treatment outcomes were achieved with lower medication doses than medication alone (mean dose: 37 vs. 31 mg/day MPH) MTA Study Multimodal Treatment Study of Children w/adhd In several non-adhd domains of functioning, combined treatment was superior to MTA medication management, behavioral treatments and community care Oppositional defiant disorder Symptoms of depression and anxiety Teacher rated social skill deficits Parent-child relationships Reading achievement 8

9 Case # 2: ADHD Complex 12 yo girl with ADHD (primarily inattentive type) associated with Anxiety Case # 2: 12 yo girl with ADHD (I) + Anxiety Stimulant alone (or atomoxitine) Stimulant and cognitive-behavioral therapy Atomoxitine and cognitive behavioral therapy Stimulant or atomoxitine w / SSRI Case # 3: 15 yo boy with ADHD and depression Stimulants and atomoxetine are generally not effective with depression Bupropion (aminoketone) Dopamine and norepi reuptake inhibitor 3 RCTs: effective with ADHD +depression Off-label when prescribed for ADHD alone Stimulant or Atomoxetine + SSRI CBT; IPT 9

10 Tailoring ADHD Medications Co-existing Anxiety: Stimulant; Atomoxetine Co-existing Depression: Bupropion Co-existing aggression-increased impulsiveness: Alpha-2 agonist (guanfacine/intuniv; clonidine/kapvay) Atomoxetine may be beneficial w/ co-existing Delayed sleep onset Concern with substance abuse (patient/family) Parent refuses a stimulant Does Treatment Plan Monitor Target Behaviors? Improve social relationships with parents, siblings, teachers and peers Improve academic performance (work efficiency, completion and accuracy) Independence in self-care and homework Improve self-esteem Enhance safety in community Common Side Effects with Stimulants Appetite suppression Weight loss (or not gaining weight) Decrease height velocity Tics Sleep problems Emotional lability at 3-5 PM (LA) 10

11 Weight loss (or not gaining weight) Ask about appetite prior to starting med Anorexia gradually decreases over time for most children Focus on meals when med has worn off (breakfast, afternoon snack, dinner, bedtime) Allow grazing Encourage supplements (protein shakes, nutrition bars, instant breakfasts) California cure for weight loss in children with ADHD: the peanut butter-banana-honey shake 1-1 ½ frozen bananas 2 large tablespoons of peanut butter Honey Milk Blend for a shake in a blender Long-term Stimulant Therapy and Growth 10-year study with control group Stimulant treatment may attenuate growth initially, but growth deficits disappear with longer follow-up as catch-up growth occurs. Decreased height growth still can occur as an adverse effect in individual patients. Close monitoring of growth and a careful discussion of stimulant benefits and risks with patients and parents are important. Biederman J et al. J Pediatr 2010 Sept;157:

12 Stimulants and Tics Tics: Were tics present prior to medication? 1/3 boys and 1/6 girls with ADHD have tics; not an absolute contraindication to stimulant treatment 15-30% of children on stimulants experience motor tics, most of which are transient When tics develop or exacerbate on stimulant medication and medication is continued: 1/3 resolve 1/3 stabilize 1/3 increase Ask: Are there vocal and motor tics? (Tourette s?) Do tics have an adverse effect on socialization? Management options: observe/monitor, d/c stimulant, add alpha-1 agonist, change treatment to atomoxetine Sleep problems (insomnia/ sleep awaking) Ask about sleep pattern prior to med Encourage sleep routine Consider decreasing morning dose With late afternoon or evening irritability, a small dose of short acting med may paradoxically organize sleep Medication: diphenhydramine, melatonin, clonidine Emotional lability at 3-5 PM each day Review mental status history re: depression and anxiety Review new psychosocial stress Decrease AM dose Add short-acting stimulant after school If mood change throughout day: May indicate poor response to med In bipolar disease, stimulants may trigger irritability or sadness Zombie effect (inertia): may indicate over-dose; decrease dose 12

13 What do we know about the natural history of children w/ ADHD? Preschool-age presentation School-age: most frequent presentation Prevalence 7-8% (across most cultures studied) In a school-age child with an ADHD diagnosis: * 2/3 persist into adolescence (less hyperactivity in some) * 1/3 persist as adults Preschool ADHD Diagnostic Challenge: separating normal preschool-age activity level and inattentiveness from ADHD Teaching parents BEHAVIOR MANAGEMENT is first-line therapy Charach A et al. Pediatrics (5) e1584 -e1604 Stimulant medication is effective but w/ less predictability and more increased frequency of side effects including low mood, irritability, somatic complaints, and insomnia. Greenhill L et al. J Amer Acad Ch Adol Psychiatr 2006; 45: ADHD in Adolescence Impulsive and inattentive behaviors predominate Impact on learning and social skills Major developmental tasks: IDENTITY formation (Erikson) and FORMAL OPERATIONS (Piaget) Increased demand on executive functions Medication diversion Driving and substance abuse risks 13

14 ADHD in Adolescence Cognitive Enhancement New York Times June 11, 2012 Stein, MT. Stimulants to enhance academic achievement. J Develop Behav Pediatr 33:589, Graf WD et al. Pediatric neuroenhancement: Ethical, legal, social and neuro-developmental implications. Neurology 2013; 80:1251. Joffe A. Against pediatric neuroenhancement. Jour Watch Pediat Adol Medicine 2013;12: 71. ADHD in syndromes associated with significant developmental disabilities Fetal alcohol syndrome Fragile X syndrome Angelman syndrome Prader-Willi syndrome Tourette syndrome Turner syndrome Williams syndrome Hagerman RJ. Neurodevelopmental Disorders: Diagnosis and Treatment (1999) New York: Oxford University Press. ADHD in Primary Care: Making it Work Assuming that 60 minutes is necessary for a comprehensive evaluation.. Three 20 minute office visits Multiple visits may be better than a single one 14

15 Non-responders to medication for ADHD Unrealistic target symptoms Lack of accurate information about behaviors Incorrect diagnosis: Time to develop a new hypothesis Coexisting condition affecting treatment Lack of adherence to treatment Treatment failure Addendum slides DSM-5: What s new for ADHD Neurodevelopmental Disorder If >17 yo: only 5 criteria needed in each domain Several IA or H/I sx prior to 12 years Descriptive examples of behaviors Autistic Spectrum Disorder not excluded In genetic dx s, ADHD presentation should be dx Other specified ADHD -clinically significant impairment but do not meet full criteria for ADHD 15

16 Does Treatment Plan Monitor Target Behaviors? Improve social relationships with parents, siblings, teachers and peers Improve academic performance (work efficiency, completion and accuracy) Independence in self-care and homework Improve self-esteem Enhance safety in community Individualizing Target Outcomes Improve core symptoms of ADHD Reduce associated symptoms Anxiety, depression, oppositional behaviors, conduct disturbance Improve functioning in education Verbal or written communication skills Completing assignments/homework Reduce supervision at school or in community Improve social relationships Target Behaviors for Adolescents Academic problems work production Impaired peer relationships Delinquent behavior Dangerous driving Substance use Impulsive sexual activity Defiance 16