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Evidence Based Assessment and Treatment of Attention Deficit Hyperactivity Disorder

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Title: Evidence Based Assessment and Treatment of Attention Deficit Hyperactivity Disorder


1
  • Evidence Based Assessment and Treatment of
    Attention Deficit Hyperactivity Disorder
  • May 14, 2010
  • Christopher K. Varley, M.D.

2
Learning Objectives
  • Refinement of diagnosis of ADHD
  • Review of evidenced based treatment of ADHD

3
  • Attention-Deficit/Hyperactivity Disorder
  • A. Either (1) or (2)
  • six (or more) of the following symptoms of
    inattention
  • have persisted for at least 6 months to a
    degree that is
  • maladaptive and inconsistent with
    developmental level
  • Inattention
  • often fails to give close attention to details or
    makes
  • careless mistakes in schoolwork, work, or
    other activities
  • (b) often has difficulty sustaining attention in
    tasks or play activities
  • (c) often does not seem to listen when spoken to
    directly

4
  • Inattention (continued)
  • often does not follow through on instructions and
    fails to finish schoolwork, chores, or duties in
    the workplace (not due to oppositional behavior
    or failure to understand instructions)
  • often has difficulty organizing tasks and
    activities
  • often avoids, dislikes, or is reluctant to engage
    in tasks that require sustained mental effort
    such as schoolwork or homework
  • often loses things necessary for tasks or
    activities (e.g., toys, school assignments,
    pencils, books, or tools)
  • (h) is often easily distracted by extraneous
    stimuli
  • (I) is often forgetful in daily activities

5
  • (2) six (or more) of the following symptoms of
    hyperactivity-impulsivity have persisted for at
    least 6 months to a degree that is maladaptive
    and inconsistent with developmental level
  • Hyperactivity
  • (a) often fidgets with hands or feet or squirms
    in seat
  • (b) often leaves seat in classroom or in other
    situations in
  • which remaining seated is expected
  • (c) often runs about or climbs excessively in
    situations in
  • which it is inappropriate (in adolescent or
    adults, may be
  • limited to subjective feelings of
    restlessness)

6
  • Hyperactivity (continued)
  • (d) often has difficulty playing or engaging in
    leisure activities quietly
  • (e) is often on the go or often acts as if
    driven by a motor
  • often talks excessively
  • Impulsivity
  • (a) often blurts out answers before questions
    have been completed
  • (b) often has difficulty awaiting turn
  • (c) often interrupts or intrudes on others (e.g.,
    butts into conversations or games)

7
  • B. Some hyperactive-impulsive or inattentive
  • symptoms that caused impairment were
    present
  • before age 7 years.
  • C. Some impairment from the symptoms is
    present in two or
  • more settings (e.g., at school (or
    work) and at home).
  • D. There must be clear evidence of
    clinically significant
  • impairment in social, academic, or
    occupations
  • functioning.
  • E. The symptoms do not occur exclusively
    during the course
  • of Pervasive Developmental Disorder,
    Schizophrenia, or
  • other Psychotic Disorder and are not
    better accounted for
  • by another mental disorder (e.g.,
    Mood Disorder, Anxiety
  • Disorder, Dissociative Disorder, or a
    Personality Disorder).

8
  • Code based on type
  • 314.01 Attention-Deficit/Hyperactivity
    Disorder, Combined Type if both
  • Criteria A1 and A2 are met for the
    past 6 months
  • 314.00 Attention-Deficit/Hyperactivity
    Disorder, Predominantly Inattentive
  • Type if Criterion A1 is met by
    Criterion A2 is not met for the past 6 months
  • 314.01 Attention-Deficit/Hyperactivity
    Disorder, predominantly Hyperactive-
  • Impulsive Type if Criterion A2 is
    met but Criterion A1 is not met for the
  • past 6 months.
  • Coding note For individuals (especially
    adolescents and adults) who currently
  • have symptoms that no longer meet full criteria,
    In Partial Remission should be
  • specified.
  • 314.9 Attention-Deficit/Hyperactivity
    Disorder Not Otherwise Specified
  • This category is for disorders with prominent
    symptoms of inattention or
  • hyperactivity-impulsivity that do not meet
    criteria for Attention-Deficit/Hyperactivity
  • Disorder.

9
ADHD DSM-V Changes Under Consideration
  • Drop subtypes or drop primarily hyperactive
    impulsive and inattentive subtypes
  • Change to age of onset on or before 12
  • Nuanced changes in impulsivity criteria and
    criteria for adults
  • Other disorders e.g. (Autism) will not exclude
    ADHD

10
  • ATTENTION DEFICIT
  • HYPERACTIVITY DISORDER
  • Epidemiology
  • 1) Prevalence of 3-5 school-age children 2-4
    adolescents
  • Recent studies suggest as high as 10 of
    school-age children

11
  • ADHD
  • Etiology
  • No single cause to explain the vast majority of
  • ADHD cases
  • Data support a biologic basis for ADHD
  • Future research may more fully elucidate the
  • roles of neurophysiology, genetics, and
  • environment in producing this disorder
  • Rising research on the Dopamine system, but
  • not consistent findings

12
  • Genetic Study Summary
  • Adult relatives of children with ADHD have
  • elevated rates of ADHD
  • Child relatives of adults with ADHD have
  • elevated rates of ADHD
  • Molecular genetic findings are similar for
  • children and adults

Faraone SV, et al. J Consult Clin
Psychol200068830-842

13
  • ADHD ETIOLOGY
  • Imaging Studies Summary
  • Results support prominent role of
  • frontal lobe dysfunction in ADHD
  • cortical-subcortical circuits
  • Neuroimaging techniques have not been validated
    as tools for ADHD diagnosis or to inform
    treatment and are very expensive

14
RATING SCALES
  • Narrow Band ADHD Scales
  • Conners
  • Vanderbilt
  • Broad Band
  • CBCL

15
  • Course of Disorder
  • 1) Earliest presentation is in toddlers
  • 2) 2/3 of adolescents diagnosed as children
  • with ADHD have symptoms
  • 3) At least 1/3 of adults diagnosed as children
    with
  • ADHD have important symptoms
  • 4) Symptom course tends to be from motoric
  • in younger children to cognitive in
  • adolescents and adults

16
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17
  • Comorbidity
  • 1) 40 of ADHD children have another
  • disruptive behavior disorder
  • 2) 30 of ADHD children also have an anxiety
  • disorder or mood disorder
  • 3) A similar pattern of comorbidity is present
    for
  • adolescents and adults. It is also
    especially
  • important to screen for alcohol and drug
  • abuse
  • 4) 50 have Axis I condition of one or more
  • specific developmental disorders

18
  • ADHD and Psychoactive Substance Use Disorders
    (PSUD)
  • 4-year follow-up of a clinically referred sample
    of boys 6 to 17 years old at baseline (ADHD
    N140 control N-120)
  • no difference in the rate of alcohol or drug
    abuse between groups (15 vs 15), mean age-early
    adolescence
  • Risk for PSUD mediated by conduct disorder and
    bipolar disorder with or without ADHD
  • Adults with ADHD (N-139) vs controls (N-268)
  • significantly greater lifetime rate of PSUD than
    controls (55 vs
  • 27)
  • Age of onset of PSUD in subjects with ADHD
    averaged 3 years
  • earlier than controls (late adolescence/early
    adulthood)
  • ADHD was a significant risk factor independent of
    comorbid
  • diagnoses
  • Biederman et al., JAACAP 1997-3621
  • Biederman et al., BioPsychiatry 199844269

19
  • ADHD
  • Motor Vehicle Driving__________________
  • Study of 16 to 22 year olds
  • 35 with ADHD (not on medication)
  • 36 controls
  • Significantly more drivers with ADHD
  • drove without a license
  • had licenses revoked or suspended
  • had multiple crashes (2)
  • had multiple traffic citations (3), especially
    for speeding

Subgroups of ADHD with comorbid oppositional
defiant or conduct disorder were at highest risk
Barkley et al. Pediatrics 199392-212
20
Trials Suggest Improved Driving on Methylpenidate
21
CURRENT ISSUES REGARDING ADHD
  • Sleep Problems
  • Sleep problems are common in ADHD
  • Poor sleep interferes with concentration
  • Sleep apnea does occur in kids and treating it
    help attention span
  • Not clear that sleep apnea is a common cause of
    ADHD
  • Should screen for problems with sleep

22
Bipolar Disorder 1. Current controversy
2. Relationship of adult to childhood
disorder 3. Prevalence in childhood and
adolescence 4. Relation of Bipolar
disorder to ADHD
23
Most Important Studies
24
MTA Multiple Center Study 14 months
25
Much better outcome with intensive expert
treatment vs community clinical
results Study vs Community Comparison Mean
Dose of methylphenidate 35mg/day
20mg/day Given 3 x day Given 2 x day 1 visit
per month 1 visit per year 30 minute session
18 minute session Regular School Contact Rare
school contact
26
  • Combined behavioral and medication vs medication
    alone
  • 1) No differences in degree of improvement of
    ADHD symptoms in combined vs medication
  • 2) Lower doses of medication in combined vs
    medication alone
  • Better outcome in combined Rx on social skills,
    aggression, arguing, anxiety, academics
  • 4) Specificity of response outcome related to
    child (e.g., anxiety) and parental variables
    (e.g., depression or substance abuse)

27
  • MTA - Longer Term Follow-up
  • Effects of active treatment not
  • as robust after closure of trial
  • Patients with less morbidity
  • have better outcomes
  • Concerns regarding growth
  • on stimulants

28
PATS Greenhill, et al
  • Preschoolers with ADHD
  • RCT with methylphenidate

29
PATSResults
  • Largest Study To-Date
  • Positive Response
  • Lower Doses
  • Higher Side Effects

30
TREATMENT
31
  • Treatment
  • 1) Medication alone is not enough
  • 2) Multimodal
  • a) Medication used judiciously
  • b) Parent and patient education
  • c) School consultation
  • d) Support for family
  • e) Social skill training, behavior
    management treatment and
  • psychotherapy if indicated
  • f) Vocational counseling
  • 3) Duration of treatment is dependent on
    duration of
  • symptoms, persistent evidence of response
    and relative
  • freedom from side effects
  • 4) Attention to treatment of comorbid symptoms
    is essential

32
Benefits of Psychosocial treatment
  1. Disruptive symptoms
  2. Anxiety/Depressive symptom
  3. Tutoring

33
Considerations
  • Homework
  • After school activities
  • Sports
  • Drama
  • Jobs
  • Driving

34
Enduring Interest in Alternative Treatments
  • Diet - sugar, red dye
  • Biofeed
  • Iron and Zinc supplements
  • Omega-3 Fatty Acids
  • No controlled trial evidence of benefit

35
  • Medication for ADHD
  • I. Primary - Stimulants a)
    Methylphenidate (Ritalin, Metadate ER, CD
  • Concerta, Methylin)
    b) Dextroamphetamine (Dexedrine,
  • Dextrostat) c)
    Amphetamine/Dextroamphetamine (Adderall
    Vyvanse)
  • d) Dexmethylphenidate (Focalin)
  • FDA approval to Rx ADHD for children 6 and
    over
  • FDA approval to Rx ADHD for children 3 and
    over



36
  • Medication for ADHD
  • Secondary
  • Atomoxetine (Strattera)
  • Alpha - 2 Agonists
  • Clonidine (Catapres)
  • Guanfacine (Tenex Intuniv)
  • Other Antidepressants
  • Bupropion (Wellbutrin)
  • Venlafaxine (Effexor)
  • Tricyclic Antidepressants
  • Imipramine (Tofranil)
  • Nortriptyline (Pamelor)
  • Desipramine (Norpramin)
  • Modafinil (Provigil)

37
Longer Acting Stimulants
  1. Offer hope of once-a-day dosing
  2. Better acceptance
  3. More costly

38
  • METHYLPHENIDATE
  • 1) Dose Generally, 5-80mg/day
  • not more than 2 mg/kg/day2) q.d. to
    q.i.d. dosing, depending on
  • patient and form of medication
  • 3) Optimize dosing
  • 4) Side effects a) Decrease in
    appetite b) Sleep problems c)
    Tics d) Irritability/Depression 5)
    Tolerance (can occur with all stimulants), with
    need
  • for dose advance or switch to
    alternative medication

39
  • Methylphenidate (continued)
  • 6) Available in multiple preparations
  • a) Ritalin 5, 10 and 20mg regular acting
    20mg
  • sustained release Ritalin LA 10, 20,
    30, 40mg with
  • 50/50 immediate/extended release beads
    ratio
  • b) Metadate ER and CD
  • c) Concerta
  • d) Methylin available in 5, 10, 20mg
    regular
  • acting methylphenidate and in 10 and
    20mg
  • extended release (ER) tablets
  • e) Transdermal patch (Daytrana)

40
  • Dexmethylphenidate (Focalin)
  • Active isomer of methylphenidate
  • Twice as potent

41
  • Focalin XR
  • Capsule immediate release
  • (IR) and extended release
  • (ER) beads in 50/50 ratio
  • Duration of action 6-12
  • hours

42
  • DEXTROAMPHETAMINE
  • 1) Dose 5-50mg
  • 2) Generally similar to Methylphenidate twice
  • as potent with equal efficacy
  • 3) Available in 5mg (Dexedrine and
  • Dextrostat) and 10mg tablets (Dextrostat)
  • and longer acting 5,10 and 15mg spansules
  • (Dexedrine)

43
  • Dextroamphetamine/Amphetamine
  • 1) Combination of amphetamine 25 and
  • dextroamphetamine 75
  • 2) Generally similar to methylphenidate, twice
    as
  • potent with equal efficacy
  • 3) Duration of action longer than
    methylphenidate
  • 4) Available in 5,10,20, and 30mg immediate
    release generic and Adderall tablets, and in
    long acting generic and Adderall XR- longer
    acting capsule form

44
Lis-dexamphetamine Dimesylate
  • Amphetamine prodrug, an amphetamine bound to
    lysine
  • Inactive initially, converted in gut
  • Possibly lower abuse potential re injection or
    inhalation
  • Report of consistent long duration of action
  • FDA approval, 2-07, still as a Schedule II drug
  • Brand name Vyvanse
  • Released July, 2007

45
  • Dose equivalence to amphetamine not clear, but
    probably ½ as potent, multiple dose sizes up to
    70mg
  • No published trials gt 70 mg/day
  • Added benefit vs. Adderall XR not established
  • Adderall XR is off patent

46
SIDE EFFECTS OF STIMULANTS
47
Cardiovascular
48
CASES OF SUDDEN DEATH IN KIDS ON ADHD MEDICATIONS
HAVE BEEN REPORTED
49
CAUSAL AND STATISTICAL LINK NOT ESTABLISHED
50
FDA Warning (Not BLACKBOX)August 2006For All
Stimulants
  • Followed Advisory Panel 2-9-2006 recommendations
  • 8-7 vote for the FDA to display a BLACK BOX
    warning about possible cardiovascular risks
    though
  • We didnt find the sudden death data very
    persuasive
  • 15-0 for FDA to create Medication Guides
    explaining possible risk
  • Possible Cardiovascular risks
  • Psychiatric side effects, including psychosis

51
EKG Monitoring
  • Recommendation to routinely do baseline EKG made
    5-6-08 by the AHA
  • Changed shortly thereafter to a class IIB
    recommendation, by clinician choice

52
  • American Heart Association 5/2008
  • Now a Class IIa recommendation that
  • children with ADHD get a careful
  • cardiac evaluation, including an EKG
  • before starting stimulant, which means it
  • is reasonable to consider an EKG, but
  • at the physicians judgment. It is not
  • mandatory

53
Risk of Psychosis
  • 1.5 per 100 patient years of exposure
  • Pediatrics, January 2009.

54
Faraone
  • Faraone S, Biederman J, Morley C, Spencer T.
    Effect of stimulants on height and weight a
    review of the literature. J Am Acad of Child
    Adolesc Psychiatry. 200847(9)994-1009.

55
Faraone (continued)
  • Quantitative analysis of longitudinal studies of
    growth in children with ADHD on stimulant
    medication

56
Stimulants and Growth
  • Results of the meta-analysis
  • Delay in height and weight.
  • Impact of .5-1 over lifetime.
  • Attenuation over time.
  • Seem to be dose dependent.
  • MPH and d-amphetamine are similar.
  • Discontinuation can lead to normal growth.
  • Do kids with ADHD have different patterns of
    growth?

57
Recommendations
  • Treat one patient at a time regarding
    appetite/growth decisions
  • Measure height and weight
  • Unusual to have to stop or change medication as a
    result of decreases in growth velocity
  • Remember other problems can explain decrease in
    growth velocity

58
Intervention if Concerns Arise
  • No data to inform treatment
  • Change diet
  • Change meds
  • Consider D/C of meds
  • Consider endocrinology referral

59
TICS
  • Contraindication per FDA
  • May not be contraindicated in reality
  • Do need to discuss with patients and families

60
  • Atomoxetine (Strattera)
  • NA reuptake inhibitor
  • Multiple trials with ADHD benefit in children,
    adolescents and adults
  • Released January 2003

61
  • Atomoxetine
  • Dose for children 1.4mg/kg/day adult
  • mean dose 93/mg/day may need to go
  • higher
  • qd or bid
  • Metabolized by Cytochrome p450 2D6-
  • interaction with fluoxetine

62
ALPHA-2 AGONISTS
63
Alpha-2 agonists 1. Clonidine a) Dose
.05-.4mg/day bid to qid patch
(hypersensitivity) b) Primary symptom relief
with hyperactivity and aggression c) May
reduce stimulant dose requirement d) Side
effects 1) Sedation 2)
Hypotension 3) Depression e)
Tolerance is common f) Rebound hypertension
is common during withdrawal tapering is
necessary g) Some capacity to reduce tics
h) Reports of sudden death in combination with
stimulants- not a clear relationship
64
Alpha-2 Agonists 2. Guanfacine a) Dose
0.5 to 4.0 mg/day in divided doses
b) Similar effect but with longer
half-life (18 vs 2 1/2 hours) c)
Possibly fewer side effects, especially
less sedation vs clonidine
65
Guanfacine(Intuniv)
  • Long-acting preparation
  • Two positive industry sponsored RCTs
  • FDA approved, 2009
  • No evidence of superiority of Intuniv over
    multiple doses of immediate release guanfacine
  • Contains 60 guanfacine

66
Alpha 2-agonist
  • Often used in addition to a stimulant to address
    motor restlessness not improved by a stimulant
  • Also used for sleep initiation, especially
    clonidine

67
  • Bupropion (Wellbutrin)Activating
    antidepressantDosage 50-300 mg/day
  • 4 of 5 studies with positive effect
  • Side effects
  • seizures 4/1000, less with long acting
    preparation
  • agitation
  • anorexia
  • tics
  • Now with XL qd preparation

68
MODAFINIL
  • EFFICACY
  • Response rate 60-65
  • Effect size .75, moderate
  • Efficacy similar to atomoxetine, but less than
    stimulants

69
Modafinil
  • Additional safety concerns raised by the FDA
  • Sent back to company for further review of the
    safety concerns by FDA
  • Application then withdrawn by Cephalon

70
Comparison Studies
71
  • Comparison Studies Have All Been
  • Industry Sponsored
  • Have to consider results in
  • that context

72
Newcorn
  • Newcorn JH, Kratochvil CJ, Allen AJ, Casat CD,
    Ruff DD, Moore RJ, et al. (2008). Atomoxetine and
    osmotically released methylphenidate for the
    treatment of attention deficit hyperactivity
    disorder acute comparison and differential
    response. The American Journal of Psychiatry. 165
    (6), 721-30.

73
Newcorn (continued)Atomoxetine vs. MPH (OROS)
  • COMPLEX DESIGN
  • 6 week, double-blind, placebo-controlled parallel
    design study trial.
  • N516.
  • Ages 6-16 years.
  • ADHD, any subtype.
  • Atomoxetine MPH placebo 331.
  • Atomoxetine dose (0.8-1.8 mg/kg/day) mean dose
    1.45 mg/kg/day
  • MPH (OROS) dose 18 54 mg/day mean dose 40
    mg/day

74
Atomoxetine vs. MPH (OROS)
  • Response Rates
  • OROS MPH 56.
  • Atomoxetine 45.
  • Placebo 24.

75
Atomoxetine vs. MPH (OROS) (continued)
  • After 6 weeks patients switched from MPH (OROS)
    to Atomoxetine for 6 weeks
  • No washout period in transition

76
Atomoxetine vs. MPH (OROS)
  • 43 of Non-Responders to MPH responded to
    Atomoxetine
  • 42 of Non-Responders to Atomoxetine responded to
    MPH

77
Summary
  1. Both atomoxetine and OROS MPH effective
  2. Response greater with OROS MPH
  3. Significant percentage of Atomoxetine
    nonresponders will respond to OROS MPH and vice
    versa

78
  • Metadate CD vs Concerta
  • (COMACS)
  • Clinical Effect Correlated with
  • Serum MPH Level
  • Both Superior to Placebo

79
  • Ritalin LA vs Concerta
  • 2 studies
  • In both studies active drug
  • significantly better than placebo

80
Morning superiority of Ritalin LA vs Concerta
81
Choice and Dosage of ADHD Medications
82
IMPORTANT
  • Two most common mistakes re medication
  • Not optimizing dose
  • Not switching to alternative medication if first
    agent not helpful

83
Generally
  • Stimulants first, then consider atomoxetine or
    alpha-2 agonists

84
Stimulants Overall pharmacodynamics are
informed by pharmacokinetics
85
Need to shape medication plan to childs familys
needs re duration of effect
86
Single Dose/Day may not be Enough
87
  • Efficacy of Stimulants
  • About ¾ of patients with ADHD respond to a single
    stimulant
  • Of the ¼ who dont respond to one class of
    stimulant, about ½ will respond to a stimulant of
    a different class (e.g., amphetamine after
    methylphenidate or methylphenidate after
    amphetamine)
  • Response rate to one class of stimulant probably
    about the same as to another class. Metanalysis
    by Faraone suggests small advantage of Adderall
    versus methylphenidate.

88
FDA Dosage Limits
  • OROS Methylphenidate (Concerta) 72mg
  • Transdermal Methylphenidate (Daytrana) 30mg
  • Dexmethylphenidate extended release (Focalinx R)
    30mg
  • Mixed salts Amphetamine Extended Release
    (AdderallXR) 40mg
  • Amfetamine-lysine (Vyvanse) 70mg

89
ADHD Symptoms in Autistic Spectrum Disorders
  • Emerging evidence for some benefit with
  • Methylphenidate
  • Guanfacine
  • Atomoxetine
  • Degree of response is attenuated

90
Substance Abuse
  • In controlled settings, evidence of benefit with
    stimulants

91
No evidence that medication of ADHD leads to
substance abuse and may help prevent it
92
Do need to be aware of diversion
93
If concerns re substance abuse by patient/parent
or diversion options
  • Atomoxetine
  • Vyvanse
  • Daytrana

94
Anxiety and ADHD Controlled Trials
  • Benefit with stimulants
  • Benefit with atomoxetine

95
Treat first things first
96
Essentially no clinical effectiveness trials at
higher doses and trials show side effects
97
In practice higher doses are prescribed
98
In general, the higher the dose the more cautious
in approach to cost/benefit guidelines
99
  • Recent Trials Indicate Benefit of Combining
    Stimulant and Atomoxetine
  • Should be reserved for cases with failure to
    respond to single agents

100
  • Combinations of Medications
  • 1) To manage partial response to ADHD
  • e.g., 1) Cant sustain effect
  • 2) Side effect management
  • e.g., 1) sleep disturbance
  • 2) rebound
  • 3) moodiness or irritability
  • 3) Comorbid disorders

101
  • Combined Pharmacotherapy
  • Common practice
  • Practice far exceeds data
  • base, controlled or open
  • trials

102
SUMMARY
103
Practical Points
  1. Optimize ADHD Treatment
  2. Monitor Target Symptoms Side Effects
  3. Then Attend to Comorbid Disorders

104
How Long Do you Treat?
  • Common illness with high potential for chronicity
  • No set end point
  • Usually Rx successfully through a whole school
    year
  • Periodic analysis of cost/benefit analysis
  • Periodic effort to withdraw

105
REFERENCES American Academy of Child and
Adolescent Psychiatry. Practice parameters for
the assessment and treatment of children,
adolescents, and adults with attention-deficit/hyp
eractivity disorder. J Am Acad child Adolesc
Psychiatry. 1997361-15. American Academy of
Pediatrics. Clinical practice guidelines
diagnosis and evaluation of the child with
attention-deficit/hyperactivity disorder.
Pediatrics. 2000105(5)1158-1170. American
Academy of Pediatrics. Clinical practice
guideline treatment of the school-aged child
with attention-deficit/hyperactivity disorder.
Pediatrics. 2001108(4)1033-1044.
106
Angold A, Erkanli A, Egger HL, et al. Stimulant
treatment for children A community perspective.
J Amer Acad Child Adoles Psych
200039975-984 Beiderman J, Klein RG, Pine DF,
Klein DF. Mania is mistaken for ADHD in
prepubertal children. Affirmative J Am Acad
child Adolesc Psychiatry. 199837(10)1091-1093.
Jensen PS, Kettle L, Roper MT., et al. Are
stimulants over prescribed? Treatment of ADHD in
four U.S. communities. J Amer Acad Child Adoles
Psych 199938797-804.
107
  • MTA Cooperative Group. A 14-month randomized
    clinical trial of treatment strategies for
    attention-deficit/hyperactivity disorder. Arch
    Gen Psychiatry. 1999561073-1086.
  • ADHD A Complete and Authoritative Guide.
    Michael I. Reife, M.D., FAAP, Editor with Sherill
    Tippins. Amer Acad Pediatrics 2003.
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