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ADHD Treatment. Objectives. Be familiar with the evidence supporting particular forms of management for ADHD, including medication Know the different classes of stimulant medications and their potential side effects Be familiar with Atomoxetine and its potential side effects.

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objectives
Objectives
  • Be familiar with the evidence supporting particular forms of management for ADHD, including medication
  • Know the different classes of stimulant medications and their potential side effects
  • Be familiar with Atomoxetine and its potential side effects
recommendation 1 management program
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 program4
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 program5
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
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
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
objectives of the literature review
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
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 2 developing target outcomes
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

School InterventionsIndividual Education Plan 504 Plan
recommendation 3 make some recommendations
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
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
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 study15
Recommendation 3:MTA Study
  • Medication management alone
  • Medication + behavior therapy
  • > Community management
  • > Behavior management alone
the stimulants nobody does it better
The StimulantsNobody does it better
  • Short, intermediate (the “old” long-lasting), truly long acting
  • 22 studies show NO difference between methylphenidate, dextroamphetamine, or mixed amphetamine salts (Adderall)
  • Individual’s response may vary
  • NO serologic, hematologic tests needed

**EKG – based on history and risk

non stimulants second rate only 2
Non-stimulantsSecond rate-only 2
  • Tricyclic antidepressants
    • 9 studies alone
    • 4 studies =/< methylphenidate
  • Bupropion (Wellbutrin, Zyban)
  • Clonidine
    • limited studies
    • > placebo
stimulants dose determination
StimulantsDose 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
StimulantsSide effects
  • appetite suppression
  • stomachache, headache
  • delayed sleep onset
  • jitteriness
  • overfocused, dull demeanor
  • mood disturbances
stimulants side effects not
StimulantsSide 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 intermediate extended
Short Intermediate Extended

3-4 hours 5-6 hours 8-10 (12)hours

atomoxetine strattera
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
atomoxetine randomized placebo controlled dose response
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

side effects
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

efficacy of atomoxetine vs placebo in school age girls with ad hd
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

measures
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

side effects28
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

atomoxetine and methylphenidate prospective randomized open label trial
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

measures30
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
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

findings32
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 effects33
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

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

Pros and Cons
behavior therapy accept no substitutes
Behavior Therapyaccept 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
Behavior TherapyParent 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
behavior therapy examples of techniques
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
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
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
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
recommendation 4 steps in re evaluation
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
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
  • Refer to mental health
recommendation 5 follow up guidelines
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 guidelines44
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
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
Conclusion nuggets
  • ADHD is a chronic condition
  • Explicit negotiations regarding target outcomes are key
  • Stimulant and behavior therapy use are the mainstay of therapy