Download ADHD Along The Developmental Spectrum - CT-AAP

ADHD: New Meds and New
Wrinkles
Lisa B. Namerow, M.D.
Child and Adolescent Psychiatry
Hartford Hospital/Institute Of Living Mental Health Network
Associate Professor of Psychiatry and Pediatrics
University of Connecticut School of Medicine
March 29, 2012
Introduction
• Although DMS-IV suggests that ADHD
symptoms must be present before age 7,
they might not be observed or markedly
interfere with functioning before
developmental tasks exceed capabilities.
• For some, that might occur in
preschool/grade school but for others, not
until middle school, high school or beyond.
ADHD: Infant/Toddler
Years
• history of excessive perinatal
activity
• difficult to soothe
• high activity level, high distractibility
• unable to sit in bouncy chair
• “always on the go”
• play more sensorimotor than symbolic
Infant/Toddler Years
(cont’d)
Treatment plan
• anticipatory guidance
• reroute energy
• observe for other areas of developmental
difficulties(r/o PDD)
• attempt to promote “goodness-of-fit”
• Thwart ODD?
Infant and Toddler Pathways
Leading to Early Externalizing
Disorders (JAACAP, 2001)
• Looked at high-risk children with low
socioeconomic status
• At age 5.5, children with comorbid ADHD (ODD,
ODD/CD) had mothers with more agression,
depression and rejecting patterns of parenting
• ADHD alone showed no differences from the
nonproblem children in terms of maternal
characteristics or other risk factors
• Neuropsychological factors such as executive and
verbal functioning deficits seem to add to risk
ADHD: Preschool Years
• excessive motor activity
• Play remains mechanical, motor-based
rather than
• increasing need for high-stim
activities, frequent redirection
• impulsivity can become a real problem
• peer play can be impaired
• aggression may become an issue
Treatment Plan:
Preschool Years
• identify “profile”: hyperactive-impulsive
versus inattentive
• access functional impairment: school,
peers, family
• assess for comorbidities (ODD, anxiety
• continue to discuss/recommend behavioral
interventions
• consider pharmacotherapy if level of
impairment is marked
PATS Study (2006): Preschool
ADHD Treatment Study
• Designed to assess methylphenidate efficacy in
preschool children
• Effect size in MTA .9-1.2 75-80%
• Effect size in PATS (0.4-0.8)
• in PATS, more side effects & intolerance (11%
discontinued) and impact on growth rates
• All of which suggests a higher threshold for
pharmacotherapy
Treatment Plan (cont’d)
• Remember: reducing hyperactivity/impulsivity can
help maintain developmental trajectory and
reduce “failure”
• These children can often feel really bad about
getting in trouble all the time
• Although “difficult” or “challenging”, they still
need the same encouragement/support positive
parental feedback but, it is occurs with much less
frequency than “easy” temperament child
Comorbidities: Preschool
Years
• r/o more global developmental
disorders (MR, PDD’s)
• Consider other learning disorders
(expressive language, executive
functioning, other language-based or
nonverbal (LDL)
• anxiety disorders
• mood disorders (Bipolar or Unipolar))
ADHD: School Age (More
Classic Presentation)
• 3 subtypes: hyperactive-impulsive,
inattentive, combined-type
• use of behavioral checklists most
appropriate
• Vanderbilt checklist approved by NICHQ
& AAP
• Assess for comorbidity
DSM-IV Criteria for ADHD
I. Either A or B:
Six or more of the following
symptoms of inattention have been present for at least 6
months to a point that is disruptive and inappropriate for developmental level:
Inattention
Often does not give close attention to details or makes careless mistakes in schoolwork, work, or other activities.
Often has trouble keeping attention on tasks or play activities.
Often does not seem to listen when spoken to directly.
Often does not follow instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to
oppositional behavior or failure to understand instructions).
Often has trouble organizing activities.
Often avoids, dislikes, or doesn't want to do things that take a lot of mental effort for a long period of time (such
as schoolwork or homework).
Often loses things needed for tasks and activities (e.g. toys, school assignments, pencils, books, or tools).
Is often easily distracted.
Is often forgetful in daily activities.
Six or more of the following symptoms of hyperactivity-impulsivity have been present for at least 6 months to
an extent that is disruptive and inappropriate for developmental level:
Hyperactivity
Often fidgets with hands or feet or squirms in seat.
Often gets up from seat when remaining in seat is expected.
Often runs about or climbs when and where it is not appropriate
(adolescents or adults may feel very restless).
Often has trouble playing or enjoying leisure activities quietly.
Is often "on the go" or often acts as if "driven by a motor". Often talks excessively.
(CONT’D)
DSM-IV Criteria for ADHD
I. Either A or B:
Six or more of the following
Often blurts out answers before questions have been finished.
Often has trouble waiting one's turn.
Often interrupts or intrudes on others (e.g., butts into conversations or games).
Some symptoms that cause impairment were present before age 7 years.
Some impairment from the symptoms is present in two or more settings (e.g. at school/work and at home).
There must be clear evidence of significant impairment in social, school, or work functioning.
The symptoms do not happen only during the course of a Pervasive Developmental Disorder, Schizophrenia, or other
Psychotic Disorder. The symptoms are not better accounted for by another mental disorder (e.g. Mood Disorder,
Anxiety Disorder, Dissociative Disorder, or a Personality Disorder).
Based on these criteria, three types of ADHD are identified:
ADHD, Combined Type: if both criteria 1A and 1B are met for the past 6 months
ADHD, Predominantly Inattentive Type: if criterion 1A is met but criterion 1B is not met for the past six months
ADHD, Predominantly Hyperactive-Impulsive Type: if Criterion 1B is
met but Criterion 1A is not met for the past six months.
American Psychiatric Association: Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington,
DC, American Psychiatric Association, 2000. [ADHD References]
The Vanderbilt Tool
• health & history form for primary care
• teacher’s checklist & parents checklist
• initial screen includes comorbidities of
anxiety, ODD, mood (scoring easy!)
• impact on learning also documented well
• does not access for bipolar BUT if child
shows multiple comorbidities, consider
bipolar
Vanderbilt (cont’d)
• follow-up checklists reference ADHD Sx’s alone
• Scoring allows for identification of comorbidities
and differentiation of ADHD subtypes
• What about discrepancy between teacher and
parent reports?
• Anxiety can mediate impulsivity or hyperactivity
in unfamiliar settings
• Remember: Final diagnosis is a clinical one; not
from a checklist alone
Comorbidity
• Anxiety Disorders
• Mood disorders
• Other disruptive behavior disorders
(ODD/CD)
• Aggression
• Tourette’s
• Substance Use Disorders
Female Vs. Male ADHD
• Females tend to be more inattentive, less
disruptive overall but social impact can still be
significant
• On CPT testing, girls show less impulsivity (MTA,
2001)
• More associated with LD issues, but less ODD
• even impulsivity can “look” different associated
with more “social butterfly chatter” rather than
aggression or disruptive behaviors
• girls with ADHD have higher levels of anxiety,
somatic sxs; boys have higher ODD/Conduct
Disorders
Bipolar vs. ADHD
• Researchers believe that ADHD and Bipolar can
be misdiagnosed symptom overlap but it is likely
that there can be comorbidity as well
• In Bipolar children, rates of ADHD range 75-98%
• In ADHD inpatients, 22% met criteria for Bipolar
(JACAAP, 1996)
• Nasreen et al., (2000) followed ADHD children
into adulthood and noted much lower comorbidity
• Bottom line: the prevalence of ADHD is clearly
much higher than Bipolar and therefore, when
hyperactivity, impulsivity is present ADHD will be
more likely
Bipolar vs. ADHD (cont’d)
• Using a high index of suspicion, bipolar should be
considered when:
-temper tantrums are marked often lasting 3-4
hours
-thought process is markedly irrational, full of
violent content and/or threats and may contain
hallucinations
• -speech is often pressured
• -irritability is a marked finding
• -there is a strong family history
• -grandiosity, hypersexuality can be
differentiating symptoms (Geller, Carlson and
others)
School Age: Treatment
Plan
• MTA serves as guideline for treatment efficacy
(See Dev and Behav Peds, Feb, 2001)
• 4 arms: CC, Medmgt, Beh, Comb
• Medmgt, or Comb clearly superior
• Comb had interesting effects over time but was
mediated by parental attitudes, strategies
• pharmacotherapy clearly has EBM support for
ADHD (meeting full A-level criteria)
MTA Study
10-m Follow- 22-m Followup After
up After
Treatment
Treatment
14-m
Treatment
Stage
0
14
24
36
Medication Only
144 Subjects
Recruitment
Screening
Diagnosis
Random
Assignment
579 ADHD
Subjects
Psychosocial (Behavioral)
Treatment Only
144 Subjects
Combined Medication &
Behavioral Treatment
145 Subjects
Community Controls
No Treatment from Study
Assessed for 24 mo.
146 Subjects
Baseline
Early
MidEnd
Treatmenttreatment Treatment
(3 m)
(9 m)
(14 m)
Assessment Points
Follow-up
(24 m)
Recruitment
of
LNCG Cohort
Follow-up
(36 m)
14-Month Outcomes
Teacher SNAP-Inattention
3
CC
Time x Tx: F=10.6, p<.0001
Site x Tx: F=0.9, ns
Site: F=2.7, p<.02
Average Score
2.5
Beh
MedMgt
2
Comb
1.5
1
Comb, MedMgt > Beh, CC
0.5
Assessment Point (Days)
0
0
100
200
300
400
days
Teacher-Rated Inattention
(CC Children Separated By Med Use)
Key Differences,
MedMgt vs. CC:
Initial Titration
Dose
Dose Frequency
#Visits/year
Length of Visits
Contact w/schools
Average Score
2.5
2
CC-NO
MEDS
CC-MEDS
1.5
BEH
MED
1
COMB
0.5
0
100
200
300
400
Assessment Point (Days)
Nonpharmacologic
Interventions
• family psychoeducation a must
• behavior therapy should be
considered
• Social skills training if social
competency are significant issues
ADHD and School
• Impact on learning is quite variable
depending on aymptom impact
• full psychoeducational evaluation if
learning below grade level
• neuropsychological evaluation if resources
are present
• 504 plan considered vs. IDEA designation
Adolescent Years
• often won’t meet the criteria of
“symptoms present since age 7”
• clinical impact may not have been apparent
earlier because of higher IQ, better
organizational skills
• now the “bar” for social & academic
competence is higher and the “attentional
deficit” is now having greater impact
• first presentation may be as a mood or
anxiety disorder
Inattention Symptoms
DSM-IV
Symptom Domain
• Difficult sustaining
attention
• Does not listen
• No follow-through
• Cannot organize
• Loses important items
• Easily distractible and
forgetful
Common
Adolescent/Adult
Manifestations
• Poor time management
• Difficult
initiating/completing tasks,
changing to another task
when multitasking, required
• Procrastination
• Avoids tasks that demand
attention
• Adaptive behavior-self
select lifestyle, support
staff, ect.
Hyperactivity Symptoms
DSM-IV
Symptom Domain
• Squirms and fidgets
• Cannot stay seated
• Runs/climbs
excessively
• Cannot play/work
• “On the go”/”driven by
a motor”
• Talks excessively
Common
Adolescent/Adult
Manifestations
• Adaptive behavior-working
long hours, selects a lot of
activities, multiple jobs, or
a very active job
• Constant activity leading
to family tension
• Avoids situations required
low levers of activity
because easily bored
• Symptoms often felt
rather than manifested
Impulsivity Symptoms
DSM-IV
Symptom Domain
• Blurts out answers
• Cannot wait turn
• Intrudes/interrupts
others
Common
Adolescent/Adult
Manifestations
• Low frustration
tolerance –quitting a
job, ending a
relationship, losing
temper, driving too
fast
• Makes quick decisions
• Interrupts
Common Comorbid Psychiatric
Disturbances in Adolescents with
ADHD
Comorbidity
Prevalence Among
Adolescents With ADHD
Prevalence in General
Adolescent Population
Academic
20-60%
5-15%
Impairment___________________________________________
Major depressive 9-32% {average 25%}
3-5%
Disorder
_________________________________________
Anxiety disorder 10-40% {average 25%}
3-10%_________
Conduct disorder 20-56%
Unknown_______
Oppositional
20-67% {average 35%}
2-16%{average7-8%}
defiant disorder _______________________________________
Bipolar disorder
-6-10%
3-4%__________
ADHD=attention-deficit/hyperactivity disorder.
The “bio” part of a
biopsychosocial treatment plan
• Considered along with school support,
outside support
• Recent NY times article (2012)
• Always consider nonpharmacologic
options first, or at least, along with
• Utilize the EBM studies, PATS, MTA
• Consider algorithms
Pediatric Psychopharmacology:
Non-Diagnostic Considerations
• Compliance: Can this system (i.e., family and patient)
comply with twice a day or three times a day dosing?
• Past Medical History (i.e., Is there a history of tics,
liver disease, cardiac conduction abnormalities,
seizures)
• Need for Medical Monitoring: Will it be a problem for
this family if frequent blood drawing is needed?
• Is there potential for this patient or anyone in the
family to use this medication as a substance for abuse?
• Is there a potential for this patient or anyone in the
family to use this medication in a suicidal gesture?
New considerations:Genomic
Testing
• P450 analysis on 3 isoenzymes has been developed
• As a review, the P450 system is a series of
enzymes in the liver which break down “toxins”
• The analysis is based on genomic technology and
using whole blood, determines the presence or
absence of the allelles that promote the
formation of these 3 enzymes
• In doing so, enzymes can be categorized as
normal, deficient, null or ultrarapid in their
activity
• It has been determined by very smart
pharmacologists which medications are substrates
for which enzymes---some medications can even
induce or inhibit the activity of an enzyme
DNA-Guided Psychotropic Selection
Frequency of
Polymorphisms
No Gene
Alterations
9%
Double and
Triple Gene
Alterations
45%
N=577
2C9
2C19
2D6
2C19
2D6
2C9
2C19
2C9
2D6
2D6
LPH Patient
Referrals
Nov. 2009
None
2C9
2C19
Single Gene
Alterations
46%
THE STIMULANTS
Ritalin® LA: Extended-release
Delivery via SODAS™ Technology
SODAS™ is a trademark of Elan Corporation, PLC
Long-acting Methylphenidate
Medications
Concerta®
Metadate® CD
Ritalin® LA
OROS®
Diffucaps®
SODAS™
Dose
18 mg 27 mg 36 mg 54 mg
20 mg
20 mg 30 mg 40 mg
Immediate
release
22%
4 mg 6 mg 8 mg 12 mg
30%
6 mg
50%
10 mg 15 mg 20 mg
Sustained/
2nd release
78%
14 mg 21 mg 28 mg 42 mg
70%
14 mg
50%
10 mg15 mg 20 mg
Products
Formulation
Technology
Concerta® [package insert]. Moutain View, CA: Alza Corporation; 2001. OROS ® is a registered trademark of ALZA Corporation.
Metadate® CD [package insert]. Rochester, NY: Celltech Pharmaceuticals, Inc; 2002. Diffucaps ® is a registered trademark of Eurand.
Ritalin® LA [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2002. SODAS ™ is a trademark of Elan Corporation, Plc.
Comparison of Extended-release
Methylphenidate Dosage Forms
Mean d,l-methylphenidate
plasma levels (ng/mL)
20
Ritalin® 20 mg BID
Concerta® 54 mg
Metadate® CD 60 mg (3 x 20 mg)
15
Ritalin® LA 40 mg
10
5
0
0
5
10
Time (h)
Gonzalez MA, et al. Int J Clin Pharmacol Ther. 2002;40:175-184.
Data on file, Novartis Pharmaceuticals.
15
Vyvanse
• Not biologically active until cleaved during
the GI absorption process
• Reportedly has a continuous absorption
that enhances duration of action
• Can be swallowed whole or sprinkled in
water
• Less rebound?
Daytrana
• Transdermal absorption
• Lasts 9 hours
• Needs to be placed and removed
every day alternating sites
• Less ups and downs?
Long-acting stimulants:
The good news
• Less chance of abuse
• Greater chance of compliance
• Less chance of stigmatizing due to trips to
the school nurse
• Less chance of rebound
• Less chance of “ups and downs”
Long-Acting Stimulants: The
Bad News
• May have greater potential for weight loss
• May have greater potential for agitation: ?
More potent
• May have greater chance for sleep
disturbance
• Take home: tolerance of short-acting
stimulants does not assure tolerance of
long-acting preparations but the longacting agents offer some clear advantages
if well-tolerated
The nonstimulants
Strattera: The first NRI
• A completely different class of medication
for ADHD, a norepinephrine reuptake
inhibiter
• Not a controlled medication
• The first nonstimulant approved by the
FDA for age 6 and over for ADHD
• Works by establishing a steady state, so
needs to be taken daily rather than as
needed
• Yet, seems to have a rapid onset of action
Alpha 2 Agonists
•
•
Mechanism: alpha 2 stimulants
cause the presynaptic
noradrenergic receptor to decrease
sympathetic output over time, this
is a brake on the release of
norepinephrine.
Approved for HTN in adults but
used in children for treatment of
tics, ADHD, and aggression.
Guanfacine ER (Intuniv)
• A long acting version of Tenex
• May have less sedation
• FDA approved for ADHD in children
over 6
• Would assess tolerance by using
short-acting first, then converting
• Comes in 1mg, 2mg, 3mg, 4mg
Kapvay (clonidine)
• FDA approved as an adjuvant to
stimulant meds
• Dosed twice per day
• Possibly less sedation than its short
acting version, clonidine
Medication Management: ADHD
(Texas Algorithm, July, 2005)
• ADHD
• ADHD with MDD
• ADHD with Anxiety
• ADHD with tics
• ADHD with aggression
ADHD alone
ADHD with tics
ADHD with Aggression
Medical workup and
monitoring
• EKG???: Let’s talk: JAACAP,
October 2011)
• Baseline bp, pulse, ht, weight
• Subsequent vital signs at each visit
• Impact on growth?: let’s talk again
Two Case Illustrations:
Case #1
• 14 y/o male currently in 9th grade
athletic, A-student presents for
evaluation of “depression”
• History reveals 1-year history
obsessional intrusive worries
regarding academic work, tests,
basketball practice
• MSE reveals almost rigidly anxious,
tearful young man
Case #1 (cont’d)
• parents revealed no past history or family history
initially but when questioned….psychologist saw pt
in 7th grade for “ADHD”
• thought he met criteria, but parents felt it wasn’t
an issue & grades were high
• also very (+) family history of OCD
• diagnosis: OCD with underlying ADHD
• treatment: target OCD first then ADHD
Case #2:
Adolescent ADHD
• 13 y/o 8th grade female presented with
grades,
motivation,
sadness
• In reviewing all prior grades, there was no history
of learning or attentional difficultness by teacher
comments or conferences
• when questioned, family did reference “she always
has her head in the clouds” when she isn’t being a
“social butterfly”
• DX: Depressive Disorder, NOS with R/O for
ADHD
• TX: target depression first then ADHD
College - Age
• May also be “first” presentation
• With transition lack of home-based structure
support, need for higher-level executive
functioning attentional symptoms may become
first apparent
• Response to a friend’s Ritalin does not make the
diagnosis but “might” suggest need for further
review
• Would suggest a neuropsychological if
adolescence or college is “first presentation” of
ADHD and had never before been considered or
documented
Take Home Points
• although fairly straightforward in some
individuals, ADHD can be elusive in others
• think developmentally
• sometimes, symptoms are not clinically
apparent until the tasks become
challenging enough
• some of these symptoms contribute to
success given the demands of the 21st
century (Does this then contribute to the
promotion of the “genes”?)
Take home points (cont’d)
• Literature supports that the natural
“untreated” course of ADHD places a
child or adolescent at high risk for
comorbidities such as substance use
disorders, Anxiety, Depression,
ODD/Conduct Disorder or a sense of
“failure”
Take Home Points (con’t)
• Adults can often find a nitch that works
for their individual strengths/weaknesses
• But the first 18-21 years of life can be a
real challenge
• The push for identification and treatment
of ADHD is NOT meant to simply
pathologize normal variants of behavior
but rather to promote an “at-risk” child’s
developmental trajectory