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Controversies Regarding
Attention Deficit Hyperactivity
Disorder
Presented by: Dr. Kevin Nugent
Child & Adolescent Psychiatrist
([email protected])
Disclosure Statement
No research involvements.
No financial involvements with pharmaceutical companies.
Have made educational presentations sponsored by:
SmithKline Beecham (Paxil)
Janssen-Ortho (Concerta)
Shire (Adderall XR, Vyvanse, Intuniv XR)
Purdue (Biphentin)
Astrazeneca (Seroquel)
Otsuka (Abilify)
Advisory Board involvement: Shire
ADHD Controversies:
General Scepticism
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Why all the recent “fuss’ about it?
All kids can get hyper! Does it even exist?
“But they can play lego/video games for hours!”
Is it a “real” medically-based disorder? Is it a mental illness?
How important is it really?
Don’t kids “grow out of it” anyway?
“They said I had it and look how well I turned out!”
All we talk about are the negatives…is there nothing positive about
ADHD?
ADHD Controversies:
More Specific Questions
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Why do professionals disagree about diagnosis and treatment?
My child has anxiety, ASD, LD, been through our marriage breaking
up, etc. so wouldn’t that explain the ADHD-like symptoms.
Aren’t dietary, “natural” or alternative measures safer/ better?
Aren’t meds for ADHD experimental/unsafe /over-emphasized/
addictive/ more for teacher’s benefit/ turning kids into “zombies’?
Why would you give hyper kids “stimulants”?
Will ADHD meds make them “addicted” or more likely to turn to
illicit drugs?
The medication didn’t work so my child must not have ADHD
Should medication be given continuously or can it just target school
days?
Historical perspective
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This set of difficulties has been identified for over 100
years: “Fidgety Phil” described by Hoffman in 1846.
In 1902, Still described 20 kids from “good homes with
good parents” with classic ADHD.
-3/1 male to female ratio
-questioned a likely biological/ genetic cause.
Historical perspective
Name has evolved:
-Organic Drivenness (30’s)
-Minimal Brain Damage/ Dysfunction (50’s)
-Hyperactivity or Hyperkinesis (60’s)
-ADD +/- Hyperactivity or Residual State (80’s)
-ADHD (predominantly Inattentive subtype,
predominantly Hyperactive-Impulsive subtype or
Combined type)
-ADHD (Inattentive, H-I or Combined presentation)
Core Difficulties
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Inattention= Trouble focusing, sustaining and shifting
attention, distractibility, poor following of instructions
and ease of boredom
Disorganization and time management/ procrastination
Elevated activity level (motoric +/- verbal)
Impulsivity (behavioral, verbal and cognitive)
Impatience and poor frustration tolerance/ anger
management
Emotional excitability and reactivity
Relative social and emotional immaturity
Prevalence and Persistence of
ADHD
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Children
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Ranges from 3-12%
Approx. 70% receive treatment
70% persistence of ADHD into adolescence
Up to 60% persistence of ADHD into adulthood (though
adults under-estimate their symptoms)
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Hyperactivity and impulsivity likely improve with age
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Adults
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US epidemiology study: 4.4%
WHO epidemiology study: 3.4% (range 1.2-7.3%)
Fewer than 17% receive treatment
Wender et al. NY Acad Sci, 2001; Wender H. Arch Pediatr Adolesc Med, 2002
Kessler et al. J Occup Environ Med, 2005; Fayyad et al. Br J Psych, 2007
ADHD Types: Childhood vs. Adulthood
Inattentive
Type
Combined
Type
22%
56%
Inattentive
Type
44%
Combined
Type
78%
In Childhood
In Adulthood
Spencer, 2005, Harvard Update; McGough, Smalley, McCracken et al.
American Journal of Psychiatry. September 2005, Vol. 162, Page 1621
Delayed brain growth in ADHD (3 yrs.)
From Shaw, P. et al. (2007). ADHD is characterized by a delay in cortical maturation.
Proceedings of the National Academy of Sciences, 104, 19649-19654.
Greater than 2 years’ delay
0 to 2 years delay
Ns: ADHD=223; Controls = 223
Biological Underpinnings
Statistically a difference in the size and/ or activation of the
following areas of the brain of children with ADHD:
-basal reticular formation (level of arousal and
concentration)
-prefrontal cortex (executive functions and problemsolving)
-basal ganglia and cerebellum (control of motor activity)
Neurotransmitters norepinephrine and dopamine modulate
these circuits
Cerebral Glucose Metabolism in Adults with
Hyperactivity of Childhood Onset
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Global and regional
glucose metabolism by
PET scan reduced in
adults who have been
hyperactive since
childhood
Largest reductions in:
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Premotor cortex
Superior prefrontal cortex
Copyright © 1990 Massachusetts Medical Society. All rights reserved; permission pending.
Zametkin AJ et al. Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood
Onset. N Engl J Med. 1990 November;323(20):1361-6.
Normal
With ADHD
Anterior Cingulate (Cognitive
Division) Fails to Activate in ADHD
Normal Controls
y = +21 mm
1 x 10-2
ADHD Adults
y = +21 mm
1 x 10-3
MGH-NMR Center and Harvard - MIT CITP
Bush et al. Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder
revealed by fMRI and the Counting Stroop. Biol Psychiatry. 1999 Jun;45(12):1542-52.
1 x 10-2
1 x 10-3
Heritability Co-efficient of ADHD
Breast
cancer
Asthma
Schizophrenia
Height
Hudziak, 2000
Nadder, 1998
Levy, 1997
Sherman, 1997
Silberg, 1996
Gjone, 1996
Thapar, 1995
Schmitz, 1995
Edelbrock, 1992
Gillis, 1992
Goodman, 1989
Willerman, 1973
0
0.2
0.4
0.6
0.76
Average genetic contribution based on twin studies
ADHD
Mean
Faraone SV. J Am Acad Child Adolesc Psychiatry. 2000 Nov;39(11):1455-7.
Hemminki K, Mutanen P. Mutat Res. 2001 Jan;473(1):11-21; Palmer LJ et al. Eur Respir J. 2001 Apr;17(4):696-702.
1
Other Genetic Evidence
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Adoption studies: Higher incidence of ADHD in
biological relatives if adopted child has ADHD
(even if adoptive parents do not)
ADHD Concordance Rate is >80% in identical
twins and 31% in fraternal twins
If parent has ADHD, 20 to 54% of offspring will
exhibit some form of ADHD
If a child has ADHD, 25% chance that one of
their parents will have ADHD
Etiologies of ADHD
From Joel Nigg (2006), What Causes ADHD?
Other
Perinatal
Smoking
Lead
FASD
LBW
Heritable (Genetics)
Heritable
LBW
FASD
Lead (high)
Smoking
Perinatal
Other (Toxins)
Co-occurring Disorders in
Children
ADHD
alone
31%
Tics
11%
Conduct
Disorder
14%
Mood Disorders 4%
MTA Cooperative Group. Arch Gen Psych 1999; 56:1088–96
Oppositional
Defiant
Disorder
40%
Anxiety
Disorder
34%
(n=579)
Potential ADHD Overlaps
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Sleep Disorders
Developmental Delays (esp. speech and
language and motor coordination)
Fetal Alcohol Spectrum Disorders
Specific Learning Disabilities (10-60%)
Central Auditory Processing Disorders
Attachment Disorders
Post-traumatic Stress Disorders
Making ADHD Diagnosis
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Child’s function and extent of related
symptoms in child’s key environments
Need for qualitative, behavioral
questionnaires and info from the school
Office observation not reliable/ sufficient.
Functional impairment!
Other developmental/ learning/ MH issues
Medical/ Family Mental Health/ etc.
The SNAP-IV Teacher and Parent Rating Scale
1. Often fails to give close attention to details or makes careless mistakes in schoolwork or tasks
2. Often has difficulty sustaining attention in tasks or play activities
3. Often does not seem to listen when spoken to directly
4. Often does not follow through on instructions and fails to finish schoolwork, chores, or duties
5. Often has difficulty organizing tasks and activities
6. Often avoids, dislikes, or reluctantly engages in tasks requiring sustained mental effort
7. Often loses things necessary for activities (e.g., toys, school assignments, pencils, or books)
8. Often is distracted by extraneous stimuli
9. Often is forgetful in daily activities
10. Often fidgets with hands or feet or squirms in seat
11. Often leaves seat in classroom or in other situations in which remaining seated is expected
12. Often runs about or climbs excessively in situations in which it is inappropriate
13. Often has difficulty playing or engaging in leisure activities quietly
14. Often is "on the go" or often acts as if "driven by a motor"
15. Often talks excessively
16. Often blurts out answers before questions have been completed
17. Often has difficulty awaiting turn
18. Often interrupts or intrudes on others (e.g., butts into conversations/games)
19. Often loses temper
20. Often argues with adults
21. Often actively defies or refuses adult requests or rules
22. Often deliberately does things that annoy other people
23. Often blames others for his or her mistakes or misbehaviour
24. Often touchy or easily annoyed by others
25. Often is angry and resentful
26. Often is spiteful or vindictive
27.-39. Additional items from DSM-III (1980) and DSM-III-R (1987)
Swanson et al. JAACAP 2001;40:168-79
Overview of Diagnostic Concerns re.
ADHD
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A more careful diagnostic process, preferably one with use of
quantifiable behavioral questionnaires and school input, is highly
recommended.
Need to understand that this is a “spectrum disorder” and that there
can be some situational influence on severity of symptoms.
A very significant overlap with many other learning and mental
health struggles means we should be open to this likelihood and be
prepared to review these matters carefully over time.
Issue of not over-stepping professional expertise.
Consideration for a second opinion or advocating for a psychoeducational assessment.
Significant Long-term Impact
of ADHD in Adolescents
60
ADHD
Controls
50
Subject %
40
30
20
10
0
Failed grade
Less than
high school
Stealing
Arrested
Substance
Abuse
Teen
pregnancy
Barkley et al. JAACAP 1990;29:546-57; Biederman et al. J Pediatr 1998;4:544-1; Barkley R. Attention-deficit hyperactivity disorder. A handbook for diagnosis and treatment, 2nd
ed., 1998; Biederman J, et al. Arch Gen Psych 1996;53:437-46; Weiss G, et al. JAACP 1985;24:211-20; Satterfield JH, Schell A. JAACAP 1997;36:1726-35
Potential Domains of Impairment in
Adolescent and Adult ADHD
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Occupational functioning
Educational functioning
Interpersonal/social functioning
Dating, sexual or relationship functioning
Managing personal finances
Driving a motor vehicle
Obedience to provincial/federal laws (e.g., criminal conduct)
Managing own children
Managing household
Managing substance use (responsible use of legal substances)
Health maintenance (e.g., exercise, diet, weight control)
Note: DSM-IV criteria 3 & 4 - Impairments
R. Barkley, 2003
Outcomes Regarding Education and
Employment
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More likely to repeat a grade
More likely to not complete High School
Less likely to complete university degrees
Enter workforce less skilled
More likely to be fired
Change jobs more often
Lower work performance
Outcomes Regarding Sexuality
(Barkley)
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Sexual risks: ADHD individuals…
-Sexually active earlier (15 vs 16 y)
-More sexual partners ( 13.6 vs 6.5)
-Less time per partner
-Less likely to employ contraception
-Greater teen pregnancy (38 vs 4%)
-Higher risk for STD’s (16 vs 4%)
Young Adults With ADHD Have Increased
Risk for Traffic Violations and Accidents
Subjects Responding Yes (%)
Negative Driving Outcomes From a Driving History Interview
70
P =0.003
ADHD (n=105)
60
Control (n=64)
50
40
30
P =0.001
20
P =0.001
P =0.002
P =0.007
10
0
Drove
before
licensed
12 or more
traffic
citations
Barkley RA, et al. J Int Neuropsychol Soc. 2002;8:655-672.
5 or more
speeding
citations
License
suspended
or revoked
3 or more
vehicular
crashes
Other Elevated Risks
Smoking Risk:
More likely to smoke, start earlier and
have a harder time quitting as adults
Other addictive behaviors (Video
games! Pornography. Gambling.)
Other health risks have been
documented (from increased
accidents to dental care to obesity)
Lifetime Risk for other Conditions in
Individuals with ADHD
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Anxiety Disorders (40%)
Major Depression (35%)
Learning Disabilities (20- 60%)
Bipolar Disorder (15%)
Antisocial PD (10%)
Substance Use Disorder (50% & possibly
as high as 10% by 20y)
Shekim et al., 90 & Biederman 93
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Are there some good aspects about
having ADHD?
ADHD Treatment
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Medications should be considered as one component of
a multi-modal intervention with school and learning,
parenting, behavioral, self-esteem, social skills, anger
management, recreational, etc components (as per the
needs of a particular child).
However, no other intervention has been shown to have
more than a modest impact on core ADD and ADHD
symptoms.
An enormous amount of research documents the
effectiveness (80 to 90%), robust impact, and safety of
medication intervention for ADHD.
This is the most studied area in Child Mental Health.
Other Proven Treatments
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Parent Education/ Support or groups about
ADHD
Parent Training in Child Management, especially
with co-morbid ODD or CD (responses of 6575% if <11 y., <30% if teens)
Family Therapy with Teens (30% respond)
Teacher Education & Training in Classroom
Behavior Management
Special classes or Residential Treatments ?
Alternative Treatments
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In contrast, evidence about helpfulness of dietary
restriction (food “allergy” or “sensitivity”) is that this has
only a slight impact on a small number of children
(perhaps 5 %).
Similarly the only food supplements with some evidence
of their helpfulness (Omega-3 and Evening Primrose Oil)
suggest a modest impact for some children.
If alternative treatments are considered, they should be
monitored and time-limited trials, preferably done
independent of medication trials.
Consider vitamin or nutritional supplements if child’s
nutritional intake is suspect.
Other Unproved/ Disproved Therapies
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Megavitamins, Anti-oxidants, Minerals, Blue
green algae, etc. (no proof)
Sensory Integration Training (disproved)
Chiropractic Manipulation and Naturopathic
Treatments (no proof)
Play Therapy/ Psychotherapy (disproved)
Cognitive Therapies (some limited impact in
children)
Neurofeedback (being researched)
Recommended Interventions
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Healthy nutrition (Vitamins and other as
needed supplements)
Good sleep habits (melatonin if required)
Exercise!
Ongoing involvement in positive
recreational pursuit!
Limit video games and screen time
Parental control software
New Medication Options
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Recent addition of long-acting stimulants:
Concerta = up to 12 hr. methylphenidate
Biphentin = 8 to 12 hr. methylphenidate
Adderall (or MAS) XR = 10 to 12 hr. dextroamphetamine and
amphetamine salts
Vyvanse (mg.)= dextroamphetamine made available by body
processing (non-abusable)
Stimulants can target school days only/ mainly.
Officially approved non-stimulant preparations:
Strattera (atomoxetine, an SNRI)
Intuniv XR (guanafacine XR, an alpha-2 adrenergic agonist)
Require continuous administration but more 24x7 assistance
In ADHD
Stimulants Found to Improve:
Core Symptoms
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Attention (on-task behavior,
efficiency, accuracy, memory
and neatness)
Impulsivity
Hyperactivity (less
interrupting, fidgetiness)
Anger and aggression
ADHD Practice Parameters. JAACAP 1997; 36:85S
Zametkin and Ernst. N Eng J Med 1993; 340:40
AND
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Noncompliance
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Impulsive aggression
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Parent child interactions
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Social Interactions and
peer acceptance
Compliance
CONCAN-1: Simultaneous
Remission of ODD Symptoms
Percentage of patients with remission of ODD sub-items of SNAP-IV
OROS MPH
IR MPH
70
Patients (%)
60
58%
50
40
30
35%
20
10
p=0.01
p=0.01
p=0.004
0
Week 4
Steele et al. APA 2005
Week 8
Endpoint
Advantages of New Med Options
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Ease of compliance- once daily in AM!
Not singled out to take meds at school!
More reliable serum level through school/
business day and potentially into evening.
Ongoing help with features of impulsivity,
irritability, frustration and anger problems
May reduce risk for associated syndromes (e.g.
depression, anxiety and substance use disorder)
Greatly reduced risk for diversion or abuse
New Med Considerations
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Concerta vs Adderall XR vs Biphentin:
-Some “do better”” on one family or other.
-Sometimes shifting duration of action improves
results or reduces side effects
-Adderall XR, and Biphentin have more dose
notches and can be “sprinkled”
-Vyvanse dissolvable and long duration
-Longer lasting & newer= more expensive
-MPH Extended duration is not Concerta!
Non-stimulant ADHD Meds
Strattera: Approved (6 y. to adults) for ADHD
-Overall a reduced effect size vs stimulants
-Consider if poor stimulant response, and if anxiety or
tics/Tourette’s
 Intuniv XR
-approved for 6-12 years in Canada (teens approved in US
and likely to come in Canada) as monotherapy or as a booster on top
of stimulants for ADHD; also more continuous impact
-has shown some impact for ODD symptoms
-need to monitor cardiovascular and can be sedating.
 Both are “continuous” but pricey, no ODB coverage.
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Stimulant Side Effects
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Appetite reduction/ possible weight loss
Insomnia
GI upset
Dry Mouth
Headaches
Slight increase in blood pressure and heart rate
Dysphoria/suppressed mood/ irritability
Hyperfocus or anxiety
Increase in tics or pre-existent anxiety (50%)
"ADHD in Adulthood: Assessment and Pharmacotherapy”, Craig Surman, Massachusetts General
Hospital Adult ADHD Research Program, Harvard Medical School
Stimulant Treatment is NOT Associated with an
Increased Risk of Substance Abuse
Percentage of subjects with a substance abuse disorder at
4-year follow-up
Subjects with substance
abuse disorder (%)
100%
80%
60%
40%
20%
0%
Untreated ADHD
(n=19)
Biederman et al. Pediatrics 1999;104:e20
Medicated ADHD
(n=56)
Controls (n=137)
Conclusions
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Many of the controversies about ADHD are a
function of misinformation, lack of information,
anecdotal stories or mental health stigma.
ADHD is a real, often persisting and highly
impactful condition.
In fact, this is the best studies area of child
mental health and it’s clear ADHD deserves
active, multi-modal treatment!
Not recognizing, assessing or treating ADHD
may well have impacts and “side effects”.
ADHD
The End!
Q&A