1. ADHD Evaluation & Treatment Edward J. Coll, M.D. COL, MC Chief, Developmental Pediatrics Walter Reed Army Medical Center

2. Practice Guidelines Primary care clinicians Children 6-12 years old Framework for diagnostic decisionmaking Evidence based review

4. Review and Recommendations Strong recommendation: high-quality scientific evidence or strong expert consensus Fair/weak: lesser quality, limited data, or expert consensus Clinical Options: reasonable provider

5. Recommendation #1 If inattention, hyperactivity, impulsivity, academic underachievement, behavior problems Primary care clinician needs to initiate the evaluation Good evidence Strong recommendation

6. Screening Questions How is __ doing in school? Are there any problems with learning that you/teacher see? Is your child happy in school? Are you concerned…behaviors at home/school/play with friends? Is your child having problems completing classwork or homework

7. Recommendation #2 ADHD diagnosis must meet DSM-IV criteria Symptoms and functional impairment Criteria remain subjective and no reliable measures in primary care Good evidence Strong recommendation

8. DSM-IV Criteria 6 of 9 symptoms often –Inattentive –Hyperactive/Impulsive –Combined (both) causes distress or impairment inconsistent with developmental level

9. DSM-IV Criteria starts before 7 years old lasts over 6 months two or more situations not due to: –Autism, Pervasive Dev Disorder –Mood or Anxiety Disorder –Psychotic Disorder –Dissociative or Personality Disorder

10. DSM-IV Criteria Inattention fails to give close attention to details, makes careless mistakes in schoolwork or other activities has difficulty sustaining attention to task or play activities does not seem to listen what is said to him/her

11. DSM-IV Criteria Inattention not follows through on instructions; fail to finish schoolwork, chores, duties in workplace (not due to oppositional behavior or failure to understand) difficulty organizing tasks/activities avoids/dislikes tasks that require sustained mental effort

13. DSM-IV Criteria Inattention loses things necessary for tasks or activities (school assignments, pencils, books, tools, toys) easily distracted by extraneous stimuli forgetful in daily activities

14. DSM-IV Criteria Hyperactivity/Impulsivity often fidgets with hands/feet or squirms in seat leaves seat in classroom or in other situations in which remaining seated is expected runs about or climbs excessively where inappropriate (teens or adults may be limited to subjective feelings of restlessness

15. DSM-IV Criteria Hyperactivity/Impulsivity difficulty playing or engaging in leisure activities quietly talks excessively acts as if “driven by a motor” and cannot remain still

16. DSM-IV Criteria Hyperactivity/Impulsivity blurts out answers before questions completed difficulty waiting in lines or for turn in games or group situations interrupts or intrudes on others

18. Dr. Barkley’s ADHD Graph * Level of Interest Work X “Normal” ADHD

19. Recommendation #3 Evidence of core symptoms from parents and caregivers various settings age onset; duration of symptoms degree of functional impairment Good evidence Strong recommendation

20. Recommendation #3A Rating scales are an option –Questions subjective and subject to bias –? If additional benefit Strong evidence; strong recommendation

21. Recommendation #3B Broad-band scales/questionnaires not recommended May be useful for other purposes Strong evidence Strong recommendation

22. Recommendation #4 School evidence required Core symptoms, duration Functional impairment Coexisting conditions Good evidence Strong recommendation

23. Recommendation #4A Rating scales a clinical option sensitivity/specificity >94% ? If any added benefit Strong evidence Strong recommendation

24. Recommendation #4B Global scales not recommended May be useful for other purposes Frequent discrepancies Can use other informants Strong evidence Strong recommendation

25. Recommendation #5 Assess for coexisting conditions –ODD 35 % –Conduct Disorder 26% –Anxiety Disorder 26 % –Depressive Disorder 18% Strong evidence Strong recommendation

26. Recommendation #6 Other diagnostic tests not routinely indicated –Pb; resistance to thyroid hormone –Brain imaging; EEG –Continuous performance testing sensitivity/specificity <70% Strong evidence Strong recommendation

28. Diagnosis Guidelines Conclusions Use explicit DSM-IV criteria Symptoms in >1 setting Search for coexisting conditions

29. Objectives of the Literature Review Effectiveness (short and long-term) and safety of therapies Medication and non-medication therapies Single therapy vs combination 6-12 year olds

30. Sources for Review Agency for Healthcare Research & Quality –McMaster Univ. Evidence-based Practice Center Canadian Office for Health Technology Assessment Study (CCOHTA) Multimodal Treatment Study (MTA Study) Pelham et al. review of psychosocial therapies

31. Recommendation 1: Management Program Primary care clinicians should establish a management program that recognizes ADHD as a chronic condition Strong evidence Strong recommendation

32. Recommendation 1: Management Program Prevalence 4-12% of school-age children 60-80% persist into adolescence Inform, educate, counsel, demystify –family, child Resources –local, national (CHADD, ADDA)

33. Recommendation 1: Management Program What distinguishes this condition from most other conditions managed by primary care clinicians is the important role that the educational system plays in the treatment and monitoring of children with ADHD.

34. Recommendation 2: Target Outcomes by Team The treating clinician, parents, and the child, in collaboration with school personnel, should specify appropriate target outcomes to guide management. Strong evidence Strong recommendation

35. Recommendation 2: Outcomes- maximize function Relationships –parents, siblings, peers Disruptive behaviors Academic performance –work volume, efficiency, completion, accuracy Individual –self-care, self-esteem Safety in the community

36. Recommendation 2: developing target outcomes Input –parents, children (patient), teachers 3-6 key targets realistic, attainable, measurable methods will change over time

37. School Interventions Individual Education Plan 504 Plan IDEA = Individuals with Disabilities Education Act ADHD under “Other Health Impaired” Educational Disability Services Section 504 of the Rehabilitation Act ADHD medical diagnosis Medical Disability with educational impact Accommodations

38. Recommendation 3: make some recommendations The clinician should recommend stimulant medication and/or behavior therapy as appropriate, to improve target outcomes in children with ADHD Strong evidence (medication), Fair evidence (behavior therapy) Strong recommendation

39. Recommendation 3: Efficacy of Stimulants Short-term benefits well established Core symptoms: attention, hyperactivity, and impulsivity observable social and classroom behaviors IQ and achievement testing- less effect

40. Recommendation 3: MTA Study Effects over 14 months 579 children 7-9.9 years old 4 randomized groups –medication alone –medication and behavior management –behavior management –standard community care

41. Recommendation 3: MTA Study Medication management alone == Medication + behavior therapy* > Community management > Behavior management alone

42. The Stimulants Nobody does it better Short, intermediate (the “old” long-lasting), truly long acting 22 studies show NO difference between methylphenidate, dextroamphetamine, or mixed amphetamine salts (Adderal) Individual’s response may vary NO serologic, hematologic, EKG needed

44. Non-stimulants Second rate-only 2 Tricyclic antidepressants –9 studies alone –4 studies =/< methylphenidate Bupropion (Wellbutrin, Zyban) Clonidine –limited studies –> placebo

45. Stimulants Dose determination NOT weight dependent Optimal effects with minimal side effects –nothing ventured, nothing gained Match target outcomes and timing –crucial step prior to starting

46. Stimulants Side effects appetite suppression stomachache, headache delayed sleep onset jitteriness overfocused, dull demeanor mood disturbances

47. Stimulants Side effects- NOT seizures- NO increased frequency with mph growth delay- at least one negative study Tourette syndrome –15-20% of patients have motor tics –50% of TS have ADHD –7 studies comparing stimulants vs placebo/other show NO increase in tics with stimulants

48. Short Intermediate Extended 3-4 hours 5-6 hours8-10 (12)hours

50. AtomoxetineStrattera Selective norepinephrine uptake inhibitor Little effect on dopamine or serotonin uptake Little effect on Ach, H1, alpha-2, DA receptors Well-tolerated in adult and pediatric studies

51. Atomoxetine...Randomized, Placebo-Controlled, Dose- Response... 297 children and adolescents 8-18 years old; 71 % male 70% had prior stimulant therapy Combined/Inattentive/Hyper-impulsive 63/33/2 % 37 % Oppositional-defiant disorder 1 depression, 1 anxiety disorder Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

52. Side Effects Small samples: –dizziness 9% vs 1% placebo –vomiting 6% vs 7% Weight loss dose dependent –mean 0.4kg at 1.2 mg/kg/d small pulse, BP changes no EKG changes <5% dropout rate atmx and placebo Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

53. Efficacy of Atomoxetine vs Placebo in School-Age Girls with AD/HD 52 children and adolescents 7-13 years old Combined/Inattentive/Hyper-impulsive 79/21/0 % 38.5 % Oppositional-defiant disorder 13.5% phobias Efficacy…Girls...AD/HD. Pediatrics 110:e75, 2002

54. Measures ADHD Rating Scale- Parent Conners’ Parent RS-Revised No Teacher ratings Clinical Global Impressions of ADHD Severity- Clinician Efficacy…Girls...AD/HD. Pediatrics 110:e75, 2002

55. Side Effects Small sample size subset here (279 total); so no significant differences Vomiting 19% vs 0% Abdominal pain 29% vs 14% Nausea 6.5% vs 14% ?Weight, cardiac... Increased cough 16% vs 4.8% Efficacy…Girls...AD/HD. Pediatrics 110:e75, 2002

56. Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial 228 children and adolescents 184 atomoxetine, 44 mph; 10 weeks 7-15 year old boys; 7-9 year old girls Most/all had prior stimulant therapy Combined/Inattentive/Hyper-impulsive 76/23/1 % 53% ODD, 7% major depression Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

57. Measures ADHD Rating Scale- Parent Completed ADHD Rating Scale- Parent Interview Conners’ Parent RS-Revised No Teacher ratings Clinical Global Impressions of ADHD Severity- Clinician Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

58. Findings Comparable improvement between the two mean dose 1.4 mg/kg/d extensive mtb, 0.5mg/kg/d slow mtb mph 0.85 mg/kg/d, (31mg/d) High rate of dropouts Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

59. Findings 43% of mph, 36 % atmx dropped out! 11%; 5 % because of adverse effects comparable atomoxetine wt loss avg 0.6 kg; (mph 0.1) small changes both in pulse, BP EKG, labs no problems, no differences Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

60. Side Effects Generally comparable Vomiting 12% vs 0% Abdominal pain 23% vs 17.5% (NS) Nausea 10% vs 5% (NS) ?Weight, cardiac... Cough 5% same “Thinking abnormal” 0% vs 5% (N=2) Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

61. Pros and Cons No abuse potential –adolescent usage –adult usage 24/7 coverage (No tic relationship) Novel class of med –use with stimulants, too Little data head to head vs stimulants Weight loss/vomiting Takes week(s) to effects Tolerance –“starter kit” issue –adjust if SSRI added Cost $3 vs 1/2 that

62. Modafinil ProVigil in ProAthletes

63. Modafinil (ProVigil) A non-stimulant stimulant Narcolepsy, daytime drowsiness in... Mechanism ? –Alter balance of GABA and glutamate which activates the hypothalamus –Increases metabolic rate of amygdala and hippocampus –activates hypocretin(orexin)-containing neurons, (which are disrupted in narcolepsy)

64. Modafinil in AD/HD Open-label study Once daily dosing Start 100 mg titrated to maximum 400 mg Length of time avg 4.6 weeks (range 2-7 wks) J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

65. Modafinil in AD/HD Open-label study 11 5-15 years old, M:F = 9:6 started Combined/inattentive/hyper-impulsive 12/2/1 started –2 noncompliant with protocol –1 hand-foot-mouth disease –1 adverse rxn: episodic hand tremor + MS change very mixed bag of comorbidities: PDD, TS... J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

66. Modafinil in AD/HD Open-label study AD/HD measures –Conners’ Parent and Teacher –ADHD Rating Scale IV for Parent and Teacher –Test of Variables of Attention (TOVA) Side effects Vital signs, weight J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

67. Modafinil in AD/HD Open-label study AM dose effect into afternoon Improved Conners’ and ADHD Rating Scales Improved TOVA impulsivity scores –but not inattention scores Delayed sleep (3), stomachache, headache, lightheadedness, tremors, finger-biting (1) J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

68. Modafinil BE AWAKE all you can be! WRAIR 3 doses of modafinil vs 600 mg caffeine Performance testing in sleep deprivation Enhances performance and alertness No advantages over caffeine Psychopharmacology (Berl) 2002 Jan;159(3):238-47

69. Modafinil BE AWAKE all you can be! Aeromedical Research Lab., Ft. Rucker, AL Aviator alertness and performance 6 pilots, 40 hour wakeful periods compared Placebo vs 3 x 200 mg modafinil 4/6 performance measures improved, reduced slow wave EEG, better mood, alertness side effects: vertigo, nausea, dizziness Psychopharmacology (Berl) 2000 Jun;150(3):272-82

70. Behavior Therapy accept no substitutes Behavior therapy Emotions-based therapy –e.g. play therapy-NOT efficacious in ADHD Thought patterns directed –cognitive, cognitive-behavioral therapy –NOT efficacious in ADHD

71. Behavior Therapy Parent Training 8-12 weeks with trained therapist teaches parent skills incorporates maintenance and relapses improves child’s functioning and behavior not necessarily achieves normal behavior

72. Behavior Therapy Examples of Techniques Positive reinforcement –reward for performance Time-out –removing positive reinforcement Response cost –losing advance rewards Token economy –combination

73. Behavior Therapy Meta-analyses difficult and few Must be maintained to be effective Stimulant effects much > behavioral therapy –MTA study: combination > med alone, but not a statistically significant difference –However, parents and teachers more satisfied Schools can implement –504 Plan –IEP

74. Recommendation 4: When to re-evaluate When the selected management for a child with ADHD has not met target outcomes, clinicians should evaluate the original diagnosis, use of all appropriate treatments, adherence to the treatment plan, and presence of coexisting conditions Weak evidence Strong recommendation

75. Recommendation 4: Ddx in re-evaluation unrealistic target symptoms poor information regarding child’s behavior incorrect diagnosis and/or coexisting condition interfering –ODD, conduct disorder, mood, anxiety, LD poor adherence/compliance treatment failure

76. Recommendation 4: Steps in re-evaluation Re-establish target symptoms –“team” communication Gather further information, other sources Consider consultation Consider psycho-educational testing

77. Recommendation 4: True treatment failure Lack of response to 2-3 stimulants –maximum dose without side effects –any dose with intolerable side effects Inability to control child’s behavior Interference of coexisting condition Engage vs refer to mental health

78. Recommendation 5: follow-up guidelines The clinician should periodically provide a systematic follow-up for the child with ADHD. Monitoring should be directed to target outcomes and adverse effects by obtaining specific information from parents, teachers, and the child. Fair evidence Strong recommendation

79. Recommendation 5: follow-up guidelines Team management plan –not just : “What does the doctor recommend?” Recording clinical data –flow sheet, progress note Interview, T-Con, teacher reports, report cards, checklists

80. Recommendation 5: frequency of follow-up NO controlled trials document the appropriate frequency MTA study: more frequent did better, BUT Once stable, visit every 3-6 months

81. Conclusion nuggets ADHD as a chronic condition Explicit negotiations re target outcomes Stimulant and behavior therapy use Close –treatment outcomes –failures