Transcript Clinical Practice Guideline - NCC Pediatrics Residency at

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 concerned…behaviors 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
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starts before 7 years old
lasts over 6 months
two or more situations
not due to:
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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. Barkley’s ADHD Graph *
“Normal”
ADHD
Work
X
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
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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
• IDEA = Individuals with
Disabilities Education Act
• ADHD under “Other
Health Impaired”
• Educational Disability
• Services
504 Plan
• 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
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medication alone
medication and behavior management
behavior management
standard community care
Recommendation 3:
MTA Study
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Medication management alone
• == Medication + behavior therapy*
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> 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)
• Individual’s 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
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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
Methylphenidate
Ritalin
Focalin
Intermediate Extended
5-6 hours
Ritalin 20 SR
Metadate ER
8-10 (12)hours
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
Atomoxetine...Randomized,
Placebo-Controlled, DoseResponse...
• 297 children and adolescents
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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
• 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
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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
• 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 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
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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
JAACAP 41:7, 2002
Trial
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
JAACAP 41:7, 2002
Trial
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
JAACAP 41:7, 2002
Trial
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
JAACAP 41:7, 2002
Trial
Side Effects
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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
JAACAP 41:7, 2002
Trial
Pros
• No abuse potential
– adolescent usage
– adult usage
• 24/7 coverage
• (No tic relationship)
• Novel class of med
– use with stimulants,
too
and
Cons
• 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
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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
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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!
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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
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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
• 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
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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
• 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 child’s 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
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ADHD as a chronic condition
Explicit negotiations re target outcomes
Stimulant and behavior therapy use
Close
– treatment outcomes
– failures