ADHD

Evaluation & Treatment

Edward J. Coll, M.D. COL, MC Chief, Developmental Pediatrics Walter Reed Army Medical Center

Practice Guidelines
Primary care clinicians Children 6-12 years old

Framework for diagnostic decisionmaking

Evidence based review

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

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

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 concernedbehaviors at home/school/play with friends? Is your child having problems completing classwork or homework

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

DSM-IV Criteria
6 of 9 symptoms often
Inattentive Hyperactive/Impulsive Combined (both)

causes distress or impairment inconsistent with developmental level

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

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

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

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

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

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

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

Dr. Barkleys ADHD Graph *

Normal

Work

ADHD

Level of Interest

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

Recommendation #3A
Rating scales are an option
Questions subjective and subject to bias ? If additional benefit

Strong evidence; strong recommendation

Recommendation #3B
Broad-band scales/questionnaires not recommended
May be useful for other purposes

Strong evidence Strong recommendation

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

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

Recommendation #4B
Global scales not recommended
May be useful for other purposes Frequent discrepancies Can use other informants

Strong evidence

Strong recommendation

Recommendation #5
Assess for coexisting conditions
ODD 35 % Conduct Disorder 26% Anxiety Disorder 26 % Depressive Disorder 18%

Strong evidence

Strong recommendation

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

Diagnosis Guidelines Conclusions

Use explicit DSM-IV criteria Symptoms in >1 setting Search for coexisting conditions

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

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

Recommendation 1: Management Program

Primary care clinicians should establish a management program that recognizes ADHD as a chronic condition

Strong evidence Strong recommendation

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)

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.

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

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

Recommendation 2: developing target outcomes

Input
parents, children (patient), teachers

3-6 key targets realistic, attainable, measurable methods will change over time

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

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

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

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

Recommendation 3: MTA Study

Medication management alone == Medication + behavior therapy* > Community management > Behavior management alone

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) Individuals response may vary NO serologic, hematologic, EKG needed

Non-stimulants Second rate-only 2

Tricyclic antidepressants
9 studies alone 4 studies =/< methylphenidate

Bupropion (Wellbutrin, Zyban) Clonidine

limited studies > placebo

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

Stimulants Side effects

appetite suppression stomachache, headache delayed sleep onset jitteriness overfocused, dull demeanor mood disturbances

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

Short
3-4 hours

Intermediate Extended
5-6 hours 8-10 (12)hours

Methylphenidate Ritalin Focalin

Ritalin 20 SR Metadate ER

Concerta Metadate CD Ritalin LA

Dextroamphetamine Dexedrine Dexedrine spansule Dextrostat Adderal Adderal XR

Atomoxetine Strattera
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

 297 children and adolescents

Atomoxetine...Randomized, Placebo-Controlled, DoseResponse...

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

AtomoxetineAD/HDStudy. Pediatrics 108:e83, 2001

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
AtomoxetineAD/HDStudy. Pediatrics 108:e83, 2001

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

EfficacyGirls...AD/HD. Pediatrics 110:e75, 2002

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

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%
EfficacyGirls...AD/HD. Pediatrics 110:e75, 2002

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
Trial

Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label

JAACAP 41:7, 2002

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

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

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

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)
Trial

Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label

JAACAP 41:7, 2002

Pros
No abuse potential
adolescent usage adult usage

and

Cons

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

Modafinil
ProVigil in ProAthletes

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)

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

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

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

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

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

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

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

Behavior Therapy Parent Training

8-12 weeks with trained therapist teaches parent skills incorporates maintenance and relapses improves childs functioning and behavior not necessarily achieves normal behavior

Behavior Therapy Examples of Techniques

Positive reinforcement
reward for performance

Time-out
removing positive reinforcement

Response cost
losing advance rewards

Token economy
combination

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

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

Recommendation 4: Ddx in re-evaluation

unrealistic target symptoms poor information regarding childs behavior incorrect diagnosis and/or coexisting condition interfering
ODD, conduct disorder, mood, anxiety, LD

poor adherence/compliance treatment failure

Recommendation 4: Steps in re-evaluation

Re-establish target symptoms
team communication

Gather further information, other sources

Consider consultation Consider psycho-educational testing

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 childs behavior Interference of coexisting condition Engage vs refer to mental health

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

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

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

Conclusion nuggets

ADHD as a chronic condition Explicit negotiations re target outcomes Stimulant and behavior therapy use Close
treatment outcomes failures