Transcript ADHD: Recent Updates and Treatment Review

Childhood ADHD: Recent Updates
and Treatment Review
Rushiraj C. Laiwala
Attention-Deficit/Hyperactivity Disorder
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The most common childhood behavioral disorder
diagnosed in outpatient setting in United States.
ADHD has been the focus of a great deal scientificclinical research and controversy.
“Overall, ADHD is one of the best researched disorders
in medicine and overall data on its validity are far more
compelling than many other medical conditions”American Medical Association’s Council on Scientific
Affairs
( Goldman et al., 1998)
History
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1902 George Still – wrote about children with restless,
impulsive and inattentive, intense affective responses and
conduct problems.
1919 & 1920- Influenza pandemic and encephalitis lethargica
epidemic- Children who survived the flu developed similar
behavioral symptoms-Hypothesis of brain damage- “Minimal
Brain Damage Syndrome”
1937- C.Bradley- d,l- amphetamine reduced restlessness and
improved concentration in children with behavioral problems
in residential treatment center.
30 years later Keith Conners and Leon Isenberg evaluated
efficacy of dextroamphetamine for children with learning
disability and behavioral problems.
History
Early 1960s- “Minimal Brain Dysfunction”
 Late 1960s- ICD-9 & DSM- II adopted- “Hyperkinetic
Syndrome of Childhood”.
 1970- Further research suggested that the main disabilityimpaired attention and impulsivity- gross motor
overactivity was secondary.
 1980- DSM III- “Attention-Deficit Disorder” ADD.
1. With Hyperactivity
2. Without Hyperactivity
3. Residual Type.
 DSM IV- ADHD
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Definition: (DSM-IV)
ADHD is a behavioral and neurocognitive condition
characterized by developmentally inappropriate and impairing
levels of gross motor overactivity, inattention, and impulsivity.
 There are five main diagnostic criteria:
(1) an onset before age 7 years
(2) duration greater than 6 months
(3) an 18-item symptom list of which 6 of 9 inattention or 6 of 9
hyperactive/impulsive symptoms have persisted for at least 6
months to a degree that is maladaptive and inconsistent with
developmental level;
(4) some impairment in two or more settings
(5) symptoms that do not occur exclusively during the course of
a pervasive developmental disorder, schizophrenia, or other
psychotic disorder and are not better accounted for by another
mental disorder, such as depression.
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Definition: (DSM-IV)
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ADHD, Predominately Inattentive Type - 6 of 9 symptoms
of inattention,
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ADHD, Predominately Hyperactive-Impulsive Type-6 of 9
symptoms of hyperactivity/impulsivity
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ADHD, Combined Type- 6 of 9 symptoms in both areas.
Proposed Revision for DSM V
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http://www.dsm5.org/ProposedRevisions/Pages/proposedr
evision.aspx?rid=383#
Comparative Nosology
ICD-10
DSM-IV-TR
Hyperkinetic Disorder (HD)
ADHD
Minimum criteria: 6 of 9 Inattentive and 3 Criteria: 6 of 9 Inattentive or 6 of 9
of 5 Hyperactivity and 1 of 4 impulsive
Hyperactivity/impulsive or Both.
Can not diagnose HD if criteria for
emotional disorder are met (Depression
or Anxiety)
Can diagnose ADHD even if criteria for
emotional disorder met
Cases not meeting HD criteria- Must be
managed psychologically before
medication can be started.
Out of 579 children with DSM-IV ADHD, Combined Subtype, from Multimodal
Treatment Study (MTA trial), only 25% met the diagnostic criteria for HD.
EPIDEMIOLOGY
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Polanczyk and colleagues estimated worldwide prevalence to be 5.2
percent. (meta-analysis that included hundreds of articles and more
than 100,000 patients).
Significant geographical variability and local variability among studies.
Prevalence in N. America is higher than Africa, Europe and Middle
East.
According to CDC data,
Approximately 9.5% or 5.4 million children 4-17 years of age have
ever been diagnosed with ADHD (2007)
The percentage of children with a parent-reported ADHD
diagnosis increased by 22% between 2003 and 2007.
Boys (13.2%) were more likely than girls (5.6%) to have ever been
diagnosed with ADHD
Prevalence of parent-reported ADHD diagnosis varied
substantially by state
State-based Prevalence Data of ADHD
Diagnosis
2003
2007
Stimulant Use - Steady Rise.
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National Institutes of Health (NIH) and the Agency for
Healthcare Research and Quality (AHRQ):
Use of Stimulant Medication,
1987- 0.6 %
1997- 2.7 %
2008- 3.5 %
Use among 6-12-year-olds was highest, going from 4.2
percent in 1996 to 5.1 percent in 2008.
Fastest growth of use among 13-18-year-olds, going from
2.3 percent in 1996 to 4.9 percent in 2008.
What Causes ADHD?
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Exact cause unknown
Meta-analysis of 83 studies with more than 6,000 subjects showed
that patients with ADHD have impairments in the executive
functioning domains of response inhibition, vigilance, working
memory, and some measures of planning (Willcutt et al., 2005).
A growing consensus that the condition involves functional and
anatomical dysfunction in the brain's frontal cortex and basal ganglia
segments of the cortico-basal ganglia-thalamo-cortical circuitry.
So what causes this dysfunctionGenetics
Neuroanatomical
Neurotransmitter
Environment
Brain Injuries
Genetics
Twin, sibling, adoption, and family studies, have all
suggested that genetic factors play an important role in
ADHD.
1. Thyroid Receptor B Gene
2. Dopamine Type D2 Receptor Gene
3. Dopamine Transporter Gene
4. Dopamine 4 Receptor Gene
5. Dopamine β-hydroxylase (DBH)
6. LPHN3 gene (Arcos-Burgos M, et al. )
(ADHD cases where LPHN3 gene (9%) is present are
particularly responsive to stimulant medication.)
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Neurotransmitters in ADHD
Dopamine System
Molecular genetic studies have targeted genes involved in
Dopamine Regulation.
Stimulant drugs bind strongly to dopamine transporter to
prevent reuptake of dopamine back into the presynaptic
axon for metabolism.
 Noradrenergic System
Dysfunction in norepinephrine systems can explaininattention and higher levels of gross motor activity.
TCAs and Atomoxetine (potent norepinephrine reuptake
inhibitors) have shown clinical improvement.
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Neuroanatomical (Neuroimaging Research)
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Children with ADHD have reduced cortical white and
gray matter volume.Volume deficits are more pronounced
in treatment-naive children (Castellanos et al., 2002).
Decreased frontal and temporal lobe volume in children
with ADHD relative to controls (Sowell et al. 2003).
NIMH intramural researchers found that cortex is thinner
in children with ADHD and remains thin in those with
less improvement. In teens who showed improvement,
the cortex thickened on the right side( Drs. Philip Shaw
and Judith Rapoport, NIMH Child Psychiatry Branch, and
colleagues )
Neuroimaging Research
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Brain matures in a normal pattern but is delayed three years in
some regions, on average, compared to control. (Philip Shaw,
M.D., NIMH Child Psychiatry Branch)
Frontal and temporal lobe showed the greatest maturational
delay in youth with ADHD.
The motor cortex emerged as the only area that matured
faster than normal in the youth with ADHD, in contrast to the
late-maturing frontal cortex areas that direct it. This mismatch
might account for the restlessness and fidgety symptoms.
The delayed pattern of maturation observed in ADHD is the
opposite of that seen in other developmental brain disorders
like autism, in which the volume of brain structures peak at a
much earlier-than-normal age.
Neuroimaging Research
Environmental Factors.
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Studies suggest a potential link between cigarette smoking and
alcohol use during pregnancy and ADHD in children.
Preschoolers who are exposed to high levels of lead, may have
a higher risk of developing ADHD.
Sugar: The idea that refined sugar causes ADHD or makes
symptoms worse is popular, but more research discounts this
theory than supports it.
Food additives: Recent British research indicates a possible link
between consumption of certain food additives like artificial
colors or preservatives, and an increase in activity. Research is
under way to confirm the findings and to learn more about
how food additives may affect hyperactivity.
Brain injuries
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Children suffering a severe head injury may develop
symptoms of ADHD, usually of the inattentive subtype.
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However, only a small percentage of children with ADHD
have suffered a traumatic brain injury.
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Encephalopathies can cause inattention but generally
produce other neurological symptoms (language or
motor impairment) in addition to inattention.
Comorbidities
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Oppositional defiant disorder (ODD)- 50%
Some of these patients will develop conduct disorder.
Anxiety Disorder- 30-35 %
Learning Disorder and Language Problem- 25-35 %
Substance Abuse- 15-19 %
Mood Disorder- contentious issue- with various studies
indicating 0-33%
Screening:
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In any mental health assessment, ask questions regarding
major symptoms ( inattention, impulsivity and
hyperactivity) regardless of chief complaint.
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Rating scales and specific questionnaires can be included
during office/clinic registration or before the interview.
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If a parent reports that the patient suffers from any
symptoms of ADHD that induce impairment or if the
patient scores in the clinical range for ADHD symptoms
on a rating scale, then a full evaluation for ADHD should
be done.
Evaluation
Three Major Components:
1. Interview with the parents.
2. Interview with the child/adolescent.
3. Investigation & psychological testing.
Interview with the parents
A detail interview about each 18 symptoms.
 For each symptoms
Age of Onset ( Childhood )
Duration ( Chronic )
Frequency ( More days than not )
Impairment ( Do not confuse with symptom)
 Interview parent regarding common psychiatric disorders (
ODD, CD, Depression, Anxiety, tic disorder, Substance Abuse,
Psychosis)
 Family history: psychiatric illness. ( ADHD, Anxiety, Tic, CD)
 Social history: Structured Vs Disorganized
 Perinatal history, development history, milestones, medical
history and mental health history.
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Interview with the parents
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Parent should complete one of many standardized behavior
rating scales.
Request release of information- obtain similar rating scale
from school teacher.
Common rating scales:
Academic Performance Rating Scale (APRS)
ADHD Rating Scale-IV
Child Behavior Checklist (CBCL)
Conners Parent Rating Scale Revised
Conners Teacher Rating Scale-Revised
Conners Wells Adolescent Self-Report Scale
Vanderbilt ADHD Diagnostic Parent and Teacher Scales and others…
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These scales also provide information about other psychiatric
symptoms which could be comorbid with ADHD or would
suggest alternative diagnosis.
Interview with the child or adolescent
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Preschool or young school-age child (5-8 years old), interview
may be done concurrently with the parent interview.
Older children and adolescents should be interviewed
separately from parents, as they may not reveal significant
symptoms (depression, suicidal ideations, drug or alcohol
abuse) in the presence of a parent.
The interview with the child or adolescent is not to confirm
or rule out the diagnosis of ADHD. ( Young child may not be
aware of symptoms and teenage may under report symptoms)
Specific emphasis to objective features to assess vocabulary,
thought processes, and content of thought.
Investigation & Psychological Testing
For unremarkable medical history- no investigation required.
 Psychological Testing:
Not mandatory
To differentiate between ADHD and learning disorder.
Academic impairment can be from ADHD or learning disorder
or both.
1:1 Supervision- if child can perform at grade level or abovelikely from ADHD- first treat ADHD
Child engages in leisure activity that require a skill but would
avoid reading a book for examination, first treat ADHD
Presence of symptoms not from ADHD like impairment in
expressive receptive language, poor phonological processing,
poor motor co-ordination, difficulty grasping fundamental
mathematics.
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Treatment
Several interventions are effective in treating children
with ADHD, including medications and behavior therapy.
 To examine how intensive treatment with medications
compares with intensive behavior therapy, or with the
combination of the two, NIMH sponsored the Multimodal
Treatment of ADHD (MTA) study.
 The study included nearly 579 children, ages 7-9, who
were randomly assigned to one of four treatment modes:
1. Intensive medication management alone;
2. Intensive behavioral treatment alone;
3. A combination of both; or
4. Routine community care (the control group).
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Multimodal Treatment of ADHD (MTA) study
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At the end of the 14 months, all groups showed
improvement.
The medication management and combined treatment
groups showed significantly greater reduction in core
ADHD symptoms and impairment.
Combined treatment, but not medication management,
was superior to community care and intensive behavioral
treatment for oppositional and aggressive symptoms,
internalizing symptoms, teacher-rated social skills, parent–
child relationships, and reading achievement.
Multimodal Treatment of ADHD (MTA) study
MTA treatment lasted for 14 months only, after which the
children were referred back to their community providers.
 All participants, were invited to return to the MTA clinics
every one to two years for an assessment of their ADHD
symptoms and level of functioning.
 At the end of three year follow up,
A. Sustained improvement after three years.
B. Initial advantages of medication management alone or in
combination with behavioral treatment over purely
behavioral or routine community care started to wane.
C. Ratings from families and teachers favored the combination
treatment, which allowed for lower medication doses.
D. The careful management of medication by MTA physicians
produced better outcomes than medication provided
through usual community care sources.
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Multimodal Treatment of ADHD (MTA) study
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8 year follow-up,
The eight-year follow-up revealed no differences in
symptoms or functioning among the youths assigned to
the different treatment groups as children.
Youths with ADHD still had significantly more academic
and social problems compared with peers who did not
have ADHD.
Youths who had responded well to treatment and
maintained their gains for two more years after the end
of the trial tended to be functioning the best at eight
years.
Multimodal Treatment of ADHD (MTA) study
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8 year follow-up ( Continued…)
A majority (61.5 percent) of the children who were
medicated at the end of the 14-month trial had stopped
taking medication by the eight-year follow-up, suggesting
that medication treatment may lose appeal with families
over time. The reasons for this decline are under
investigation, but they nevertheless signal the need for
alternative treatments.
Children who were no longer taking medication at the
eight-year follow-up were generally functioning as well as
children who were still medicated, raising questions about
whether medication treatment beyond two years
continues to be beneficial or needed by all.
Treatment
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Begins with psychoeducation
Involves educating the parent and child about ADHD and its
various treatment options (medication and behavior therapy),
linkage with community supports and additional school
resources.
Take into account the most recent evidence concerning
effective therapies as well as family preferences and concerns.
Use books, articles, videos, and some noncommercial web sites
on ADHD to educate parents and patients.
http://www.adhdawarenessweek.org/,
http://www.nimh.nih.gov
http://www.cdc.gov and many more.
Medication (Stimulants)
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The short-term efficacy of psychopharmacological
intervention for ADHD is well established.
Methylphenidate (MPH) or amphetamine the two are
equally efficacious.
Long-acting formulations (Offers convenience and
confidentiality) are equally efficacious as the immediaterelease forms in both adolescents as well as children.
(Spencer et al., 2006; Wilens et al., 2006)
Medication (Stimulants)
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Careful titration
Teacher and parent rating scales at end of one week of
increase in dose
Equal response to both MPH and Amphetamine - 41 %
Preferential response to MPH or Amphetamine - 44 %
Initial response rate- 85% if both stimulants are tried (65% 75% response when only one stimulant is tried).
Regular monitoring.
Look for side effects,
Most common: appetite decrease, weight loss, insomnia,
headache
Less common: tics and emotional lability/irritability
Medication- Monitoring
Height and Weight:
A. Serial plotting of on growth charts.
B. Change in height or weight that shows aberrant growth
trajectory- consider drug holidays or switching medication.
Blood Pressure and Pulse:
A. MTA at 14th Month- higher heart rates but no tachycardia.
B. 10 year follow-up- Did not appear to increase the risk for
abnormal elevations in blood pressure or heart rate.
C. Epidemiological studies have indicated that even modest
elevations in heart rate may increase a person’s lifetime risk
for cardiovascular problems.
D. Persistent effect of continuous stimulant treatment on heart
rate should not be dismissed.
Medication- Monitoring
EKG:
Cases of sudden death have been reported.
 MPH: 0.2/100,000 & Amphetamine: 0.2/100,000 (exposure period January1,
1992 to December 31, 2004) (Villalaba-2006)
 Package insert- generally not be used in children and adolescents with
preexisting heart disease or symptoms suggesting significant cardiovascular
disease.
 No evidence currently indicates a need for routine cardiac evaluation (i.e.,
electrocardiography, echocardiography) before starting any stimulant
treatment in otherwise healthy individuals (Biederman et al., 2006).
 Adding ECG to the current standard of care may identify more children at
risk for SCD prior to starting them on stimulants for treating ADHD but it
is borderline cost-effective. (Dr. Peter Denchev, and colleagues, 2010)
 The American Heart Association currently recommends that doctors
consider obtaining an ECG prior to prescribing stimulants if they believe it
is warranted.
Medication- Monitoring
Tics:
A. Stimulant induced tics- less clear
B. Children with comorbid ADHD and tic disorders, on
average, show a decline in tics when treated with a
stimulant but clinicians have noticed stimulant induced
tics, too.
C. Treatment-emergent tics during a trial- consider an
alternative stimulant or a non stimulant
D. Symptoms respond adequately only to a stimulant
medication that induces tics- consider clonidine or
guanfacine (Tourette’s Syndrome Study Group, 2002)
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Medication- Monitoring
Aggression and Mood Lability:
A. Aggressive acts and antisocial behavior may decline with
stimulants (Connor et al., 2002 [rct]).
B. Stimulant induced vs Rebound
C. For rebound hyperactivity- small dose of immediate
release stimulant in the late afternoon.
D. Rare cases of aggressive behavior, psychosis and manic
symptoms reported (black box warning)
E. If stimulant induced agression, mood lability, psychosis
are evident- stop stimulant. Adjunctive therapy with
neuroleptics or mood stabilizers is not recommended.
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Medication- Atomoxetine
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Noradrenergic reuptake inhibitor.
Less pronounced effects on appetite and sleep.
Relatively more nausea or sedation.
Full therapeutic dose for at least several weeks to obtain
full effect.
Indicated for ADHD comorbid with substance abuse.
RCT showed a reduction in ratings of symptoms of both
ADHD and anxiety, when used in patient with ADHD and
co-morbid anxiety. (Sumner et al., 2005 ).
Black Box Warnings for suicidality and not approved for
major depression.
Treatment Failure with stimulant
If the patient fails to respond to trials after an adequate
length of time at appropriate doses,
1. Review diagnosis of ADHD again.
2. Consider behavioral therapy.
3. Consider alternative medications like bupropion,
tricyclic antidepressants (TCAs), and alpha-agonists.
Psychosocial Treatment
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Includes different modalities, such as psychoeducation,
academic organization skill teaching and remediation,
parent training, behavior modification, cognitive–
behavioral therapy (CBT), social skills training, and
individual therapy.
Parent training, intensive behavior modification, and social
skills training have shown most efficacy for children with
ADHD in controlled trials.
Intensive Behavioral Interventions
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Psychoeducation about the course, risk factors, and
long-term outcomes of ADHD
The parents are encouraged to attend more carefully to
their child's behavior
Parents are trained to use time out effectively.
Parents are instructed how to establish a contingency
management or token economy system at home.
Parents learn how to manage noncompliant behaviors in
public settings.
Finally, advances in prosocial behavior in school are
supported by use of a daily report card.
Psychosocial Treatment
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Examples of social skills training, how to wait for their
turn, share toys, ask for help, or respond to teasing.
Learning to read facial expressions and the tone of voice
in others, and how to respond appropriately can also be
part of social skills training.
It is crucial to evaluate the parents and family for
dysfunction related to the child's ADHD. Parental ADHD
may interfere with behavioral modification programs,
indicating that treatment of the affected parent may be
necessary before the child's intervention can be
successful.
Medications versus Psychosocial
Management
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If a patient with ADHD has a robust response to
psychopharmacological treatment and subsequently
shows normative functioning in academic, family, and
social functioning, then psychopharmacological treatment
of the ADHD alone is satisfactory.
If a patient with ADHD has a less than optimal response
to medication, has a comorbid disorder, or experiences
stressors in family life, then psychosocial treatment in
conjunction with medication treatment is often beneficial.
[(A A C A P) Practice Parameter]
References
[email protected]
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American Academy of Child and Adolescent Psychiatry (1997), Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity
disorder.
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American Academy of Child and Adolescent Psychiatry (2002), Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity
disorder.
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American Academy of Child and Adolescent Psychiatry (2007), Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity
disorder.
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Arnold LE (2000), Methylphenidate vs. amphetamine: comparative review. J Atten Disord 3:200211
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*The MTA Cooperative Group: A 14-month randomized clinical trial of treatment strategies for attention deficit/ hyperactivity disorder (ADHD). Arch Gen Psychiatry. 1999;56:1073.
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Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stephanos GA: Etiologic subtypes of attention-deficit/hyperactivity disorder: Brain imaging, molecular genetic and environmental factors and
the dopamine hypothesis. Neuropsychol Rev. 2007;17(1):39.
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Shaw P, Lerch J, Greenstein D, Sharp W, Clasen L, Evans A, Giedd J, Castellanos FX, Rapoport J. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents
with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2006 May;63(5):540-9.
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Plessen KJ, Bansal R, Zhu H, Whiteman R, Amat J, Quackenbush GA, Martin L, Durkin K, Blair C, Royal J, Hugdahl K, Peterson BS. Hippocampus and Amygdala Morphology in AttentionDeficit/Hyperactivity Disorder. Arch Gen Psychiatry. 2006 Jul;63(7):795-807.
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MTA Cooperative Group: National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: changes in effectiveness and growth after the end of treatment. Pediatrics
2004;113:762-769.
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Swanson JM, Elliott GR, Greenhill LL, Wigal T, Arnold LE, Vitiello B, Hechtman L, Epstein J, Pelham W, Abikoff HB, Newcorn J, Molina B, Hinshaw S, Wells K, Hoza B, Severe JB, Jensen PS,
Gibbons R, Hur K, Stehli A, Davies M, March J, Caron M, Volkow ND, Posner MI, for the MTA Cooperative Group: Effects of stimulant medication on growth rates across 3 years in the
MTA follow-up. J Am Acad Child Adolesc Psychiatry 2007;46:1014-1026.
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Molina BSG, Hinshaw S.P., Swanson J.M., Arnold, L.E., Vitiello B, Jensen PS, Epstein JN, Hoza B, Hechtman L., Abikoff, H.B., Elliott GR, Greenhill LL, Newcorn, JH, Wells KC, Wigal TL,
Severe JB, Gibbons RD, Hur K, Houck PR, and the MTA Cooperative Group: The MTA at 8 years: prospective follow-up of children treated for combined type ADHD in a multisite study.
J Am Acad Child Adolesc Psychiatry 2009;48:484-500.
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Kaplan & Sadock's Comprehensive Textbook of Psychiatry
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Zuvekas S and Vitiello B. Stimulant medication use in children: a 12-year perspective. American Journal of Psychiatry. Online ahead of print September 28, 2011.
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Molina BSG, Hinshaw SP, Swanson JM, Arnold LE, Vitiello B, Jensen PS, Epstein JN, Hoza B, Hechtman L, Abikoff HB, Elliott GR, Greenhill LL, Newcorn JH, Wells KC, Wigal T, Severe JB, Gibbons RD, Hur K, Houck
PR, and the MTA Cooperative Group. The MTA at 8 years: Prospective follow-up of children treated for combined type ADHD in the multisite study. Journal of the American Academy of Child and Adolescent Psychiatry.
Online ahead of print March 2009.
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Other MTA references,
http://www.nimh.nih.gov/
http://www.cdc.gov/
en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder
References
http://www.nimh.nih.gov/
http://www.cdc.gov/
en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder
Other MTA references
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The MTA Cooperative Group: A 14-Month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder (ADHD). Arch
Gen Psychiatry 1999;56:1073-1086.
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The MTA Cooperative Group: Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder
(ADHD). Arch Gen Psychiatry 1999;56:1088-1096.
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Swanson JM, Kraemer HC, Hinshaw SP, Arnold LE, Conners CK, Abikoff HB, Clevenger W, Davies M, Elliott GR, Greenhill LL, Hechtman L, Hoza, B,
Jensen PS, March JS, Newcorn JH, Owens EB, Pelham WE, Schiller E, Severe JB, Simpson S, Vitiello B, Wells K, Wigal T, Wu M: Clinical relevance of
the primary findings of the MTA: success rate based on severity of ADHD and ODD symptoms at the end of treatment. J Am Acad Child Adolesc
Psychiatry 2001; 40:168-179.
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Greenhill LL, Swanson JM, Vitiello B, Davies M, Clevenger W, Wu M, Arnold LE, Abikoff HB, Bukstein OG, Conners CK, Elliott GR, Hechtman L,
Hinshaw SP, Hoza B, Jensen PS, Kraemer HC, March JS, Newcorn JH, Severe JB, Wells K, WigalT: Impairment and deportment responses to different
methylphenidate doses in children with ADHD: the MTA titration trial. J Am Acad Child Adolesc Psychiatry 2001; 40:180-187.
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Vitiello B, Severe JB, Greenhill LL, Arnold LE, Abikoff HB, Bukstein O, Elliott GR, Hechtman L, Jensen PS, Hinshaw SP, March JS, Newcorn JH,
Swanson JM, Cantwell DP: Methylphenidate Dosage for Children with ADHD over Time under Controlled Conditions: Lessons from the MTA. J Am
Acad Child Adolesc Psychiatry 2001; 40:188-196.
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Owens EB, Hinshaw SP, Kraemer HC, Arnold LE, Abikoff HB, Cantwell DP, Conners CK, Elliot G, Greenhill LL, Hechtman L, Hoza B, Jensen PS,
March JS, Newcorn JH, Pelham WE, Richters JE, Schiller EP, Severe JB, Swanson JM, Vereen D, Vitiello B, Wells KC, Wigal T: What treatment for
whom for ADHD: Moderators of treatment response in the MTA. J Consult Clin Psychol2003;71:540-552.
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MTA Cooperative Group: National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: 24-month outcomes of treatment
strategies for attention-deficit/hyperactivity disorder. Pediatrics 2004;113:754-761.
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MTA Cooperative Group: National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: changes in effectiveness and growth
after the end of treatment. Pediatrics 2004;113:762-769.
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Swanson JM, Elliott GR, Greenhill LL, Wigal T, Arnold LE, Vitiello B, Hechtman L, Epstein J, Pelham W, Abikoff HB, Newcorn J, Molina B, Hinshaw S,
Wells K, Hoza B, Severe JB, Jensen PS, Gibbons R, Hur K, Stehli A, Davies M, March J, Caron M, Volkow ND, Posner MI, for the MTA Cooperative
Group: Effects of stimulant medication on growth rates across 3 years in the MTA follow-up. J Am Acad Child Adolesc Psychiatry 2007;46:1014-1026.
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Molina BSG, Hinshaw S.P., Swanson J.M., Arnold, L.E., Vitiello B, Jensen PS, Epstein JN, Hoza B, Hechtman L., Abikoff, H.B., Elliott GR, Greenhill LL,
Newcorn, JH, Wells KC, Wigal TL, Severe JB, Gibbons RD, Hur K, Houck PR, and the MTA Cooperative Group: The MTA at 8 years: prospective
follow-up of children treated for combined type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry 2009;48:484-500.
Thank You and Merry Christmas!!
Special Thanks to Dr. Bird, Dr. McCarley, Dr. Shulruff