Dr. Robert Quillin presents on ADHD at TAPA 2014, La Cantera Resort, San Antonio, TX - February 22, 2014

1. ADHD:
Rethinking an old diagnosis
Robert L. Quillin, MD, FAAP

2. Disclosures
Speaker and consultant for VayaPharma,
makers of Vayarin
Previous research support provided by Pernix
Therapeutics
Will discuss off label use of medications,
medical foods, and supplements.

3. Presentation Outline
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morbidity of the attention disorders
current diagnostic approach to attention
disorders
the neurobiochemistry of attention
approach to stimulant use in attention
disorders
paradigm shift in the treatment of
attention disorders

4. Faces not easy to forget

6. STATE OF THE UNION

7. ADHD Timeline

8. Impact of ADHD
 Approximately 11% of children 4-17 years of age (6.4 million) have been
diagnosed with ADHD as of 2011.
 The percentage of children with an ADHD diagnosis continues to
increase, from 7.8% in 2003 to 9.5% in 2007 and to 11.0% in 2011.
 Rates of ADHD diagnosis increased an average of 3% per year from 1997
to 2006 and an average of approximately 5% per year from 2003 to 2011.
 Boys (13.2%) were more likely than girls (5.6%) to have ever been
diagnosed with ADHD.
 The average age of ADHD diagnosis was 7 years of age
 Prevalence of ADHD diagnosis varied substantially by state, from a low of
5.6% in Nevada to a high of 18.7% in Kentucky.
http://www.cdc.gov/ncbddd/adhd/data.html#us

9. Financial Impact of ADHD
 Using a prevalence rate of 5%, the annual societal ‘‘cost of illness’’ for
ADHD is estimated to be between $36 and $52 billion, in 2005 dollars. It is
estimated to be between $12,005 and $17,458 annually per individual.
 There were an estimated 7 million ambulatory care visits for ADHD in
2006.
 The total excess cost of ADHD in the US in 2000 was $31.6 billion.
 The annual average direct cost for each per ADHD patient was $1,574,
compared to $541 among matched controls.
 ADHD creates a significant financial burden regarding the cost of medical
care and work loss for patients and family members.
http://www.cdc.gov/ncbddd/adhd/data.html#cost

10. “I CAN CALCULATE THE MOTION
OF HEAVENLY BODIES, BUT NOT
THE MADNESS OF PEOPLE”
Sir Isaac Newton

11. What exactly is ADHD?
ADHD is one of the most common neurodevelopmental disorders of
childhood.
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Initial diagnosis in childhood and often lasts into adulthood
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Children with ADHD may have
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trouble paying attention,
controlling impulsive behaviors (may act without thinking about what
the result will be),
or be overly active.
The ADHD Molecular Genetics Network. Report from the third international meeting of
the attention-deficit hyperactivity disorder molecular genetics network.
American Journal of Medical Genetics, 2002, 114:272-277.

12. ADHD defined by DSM-5
INATTENTION: Six or more symptoms of inattention for children up to age 16, or
five or more for adolescents 17 and older and adults; symptoms of inattention
have been present for at least 6 months, and they are inappropriate for
developmental level:
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Often fails to give close attention to details or makes careless mistakes in
schoolwork, at work, or with other activities.
Often has trouble holding attention on tasks or play activities.
Often does not seem to listen when spoken to directly.
Often does not follow through on instructions and fails to finish schoolwork, chores,
or duties in the workplace (e.g., loses focus, side-tracked).
Often loses things necessary for tasks and activities (e.g. school materials, pencils,
books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones).
Often avoids, dislikes, or is reluctant to do tasks that require mental effort over a
long period of time (such as schoolwork or homework).
Often has trouble organizing tasks and activities.
Is often easily distracted
Is often forgetful in daily activities.

13. ADHD defined by DSM-5
HYPERACTIVITY AND IMPULSIVITY: Six or more symptoms of hyperactivityimpulsivity for children up to age 16, or five or more for adolescents 17 and
older and adults; symptoms of hyperactivity-impulsivity have been present for
at least 6 months to an extent that is disruptive and inappropriate for the
person’s developmental level:
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Often fidgets with or taps hands or feet, or squirms in seat.
Often leaves seat in situations when remaining seated is expected.
Often runs about or climbs in situations where it is not appropriate (adolescents or
adults may be limited to feeling restless).
Often unable to play or take part in leisure activities quietly.
Often blurts out an answer before a question has been completed.
Often has trouble waiting his/her turn.
Often interrupts or intrudes on others (e.g., butts into conversations or games)
Is often "on the go" acting as if "driven by a motor“.
Often talks excessively.

14. Basic types:
1)
ADHD, predominantly inattentive type
2)
ADHD, predominantly hyperactive-impulsive
type
3)
ADHD, combined type

15. Comorbidity: the rule, not the exception

16. From: Comorbid Psychiatric Disorders in Youth in Juvenile Detention (female)
Arch Gen Psychiatry. 2003;60(11):1097-1108. doi:10.1001/archpsyc.60.11.1097

17. From: Comorbid Psychiatric Disorders in Youth in Juvenile Detention (male)
Arch Gen Psychiatry. 2003;60(11):1097-1108. doi:10.1001/archpsyc.60.11.1097

18. Tuesday, October 6, 2009
Baseball Players with ADHD
http://studentacademichelp.blogspot.com/2009/10/
baseball-players-with-adhd.html#ixzz2bFzBnnv0

19. What’s missing?
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Learning disorders
Dyslexia, dysphasia, dysgraphia
Autism spectrum disorders, including PDD and
Asperger’s syndrome
Tic disorders
Tourette’s syndrome
Congenital genetic disorders – Down syndrome,
DiGeorge syndrome, and others
Cancers – leukemia, brain tumors?

20. Don’t forget your fundamentals

21. NEURO-developmental disorder
I.
II.
III.
IV.
V.
History and Physical – with interview covering
emotional and psychosocial concerns, particularly early
development
Hearing and vision screen . . . particularly hearing
Labs
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Complete blood count – anemia due to low iron,
low B12?
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Lead level – consider your patient’s exposures
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Thyroid – too much or too little?
EEG – is it a seizure?
Behavior Checklists

22. Tools of the trade
Behavior Rating Scales
subjective evaluations by teachers and parents,
self report
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Vanderbilt Assessment Scale: 6-12 years
Conners 3rd edition: 6-18 years,
More ADHD specific vs. Conners CBRS
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SNAP-IV R: 6-18 years

24. The big players

25. Is that all to ADHD?

26. Where they act

27. Aren’t you glad that’s over?

28. To treat or not to treat?
Gold standard – The stimulant
Ritalin, Adderall, Focalin
Daytrana, Vyvanse, Quillivant XR
Other choices:
Nonstimulants – Intuniv, Kapvay, Straterra
Medical foods – Vayarin
Vitamins – B’s, D’s, Mg, Zinc

29. Where to start?
COMPARE
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4-5 years old, <50
pounds
Short acting better?
Hyperactive
Family history
Side effects
Parental ambivalence
CONTRAST
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5 years old, 50+
pounds
Long acting best?
Inattentive
New diagnosis
Comorbidities
Parental Fear

31. Prescription Medical Foods
Defined as:
“a food which is formulated to be consumed or administered enterally
under the supervision of a physician and which is intended for the
specific dietary management of a disease or condition for which
distinctive nutritional requirements, based on recognized scientific
principles, are established by medical evaluation.”
Section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3))

32. FDA Regulation of Prescription
Medical Foods
Foods
FDA GRAS for
Safety
Dietary
Supplements
No Pre-Market FDA
Approval for pre1994 ingredients
Prescription Medical
Foods
FDA GRAS for
Safety of Ingredients
-ORFDA review for new
dietary ingredients
FDA Required Clinical
Evidence for Efficacy
Prescription Drugs
FDA Approval for
Safety & Efficacy

33. Time is right for a change
Omega3 + Phosphatidylserine - Vayarin
B-vitamins: folate, B6, B12, choline –
Deplin, Cerefolin
Vitamin D
Magnesium
Zinc

34. PS-Omega-3 showed an endpoint that no
longer qualified as ADHD in the TOVA
Vaisman, N., et al., Correlation between changes in blood fatty acid composition and visual sustained attention performance in children
with inattention: effect of dietary n-3 fatty acids containing phospholipids. Am J Clin Nutr, 2008. 87(5): p. 1170-80.

35. Folate
J Pediatr. 2008 Jan;152(1):101-5.
Folate pathway genetic polymorphisms are related to attention
disorders in childhood leukemia survivors.
Krull KR, Brouwers P, Jain N, Zhang L, Bomgaars L, Dreyer Z, Mahoney D,
Bottomley S, Okcu MF.
Learning Support Center for Child Psychology, Texas Children's Hospital,
Houston, TX, USA.
CONCLUSION: Preliminary data imply a strong relationship
between MTHFR polymorphisms and the inattentive symptoms of
ADHD in survivors of childhood ALL.

36. Magnesium/Vitamin B6
Magnes Res. 2006 Mar;19(1):46-52
Improvement of neurobehavioral disorders in children
supplemented with magnesium-vitamin B6. I. Attention deficit
hyperactivity disorders.
Mousain-Bosc M1, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP
1Explorations Fonctionnelles du Système Nerveux, Centre Hospitalier
Universitaire Carémeau, Nîmes, France.
CONCLUSION: In almost all cases of ADHD, Mg-B6 regimen for at
least two months significantly modified the clinical symptoms of the
disease . . .hyperemotivity/aggressiveness were reduced, school
attention was improved. . .When the Mg-B6 treatment was stopped,
clinical symptoms of the disease reappeared . . .

37. Zinc
Acta Med Croatica. 2009 Oct;63(4):307-13.
[The role of zinc in the treatment of hyperactivity disorder in
children].
Dodig-Curković K1, Dovhanj J, Curković M, Dodig-Radić J, Degmecić D.
1University Department of Child and Adolescent Psychiatry, University
Department of Psychiatry, Osijek University Hospital, Osijek, Croatia.
kdodig@yahoo.mail
CONCLUSION: The dose of zinc sulfate used was 55 mg/day, which is
equivalent to 15 mg zinc. The improvement achieved in ADHD children
with the use of zinc sulfate appears to confirm the role of zinc
deficiency in the etiopathogenesis of ADHD. Additional studies are
needed to identify the real and efficient dose of zinc.

38. Vitamin D
Pediatr Int. 2014 Jan 13. doi: 10.1111/ped.12286. [Epub ahead of print]
Vitamin D Status in Children with Attention Deficit Hyperactivity
Disorder.
Goksugur SB1, Tufan AE, Semiz M, Gunes C, Bekdas M, Tosun M, Demircioglu F.
1Department of Pediatrics, Medical Faculty, Abant Izzet Baysal University, Bolu,
Turkey.
CONCLUSION: 25-OH-vitamin D level in ADHD group and control
group was respectively; 20.9±19.4 ng/mL and 34.9±15.4 ng/mL
(p=0.001). Our results suggest that there is an association between
lower 25-OH-vitamin D concentrations and ADHD in childhood and
adolescence.

39. C
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40. THANK YOU TAPA!