Drs. Gabriel Kaplan and Bennett Silver presented at Sage Middle School Conference

1. ADHD
New Developments
in Pharmacological
and Therapeutic
Interventions
Gabriel Kaplan, M.D.
Bennett Silver, M.D.

2. Your Faculty: Gabriel Kaplan, M.D.
• President, New Alliance Academy
• Medical Director, Bergen Regional Medical Center
• Board Certified Psychiatrist
▫ Kaplan G., Ivanov I., and Newcorn J.H. Pharmacological
Management of ADHD in Children and Adolescents. Int J Child
Adolesc Health 2010; 3(2):143–61
▫ Ivanov I., Pearson A., Kaplan G., and Newcorn J.H.
Management of Comorbid ADHD and SUD Int J Child Adolesc
Health 2010; 3(2):163-177
▫ Kaplan G. and Newcorn J.H. Pharmacological Management of
ADHD Ped Clinics North Am. 2011; 58:99–120
▫ Kaplan G. “Attention deficit hyperactivity disorder in
adolescence.” in Child Health and Human Development
Yearbook 2012 Greydanus DE, Merrick J, eds Nova Biomedical
Books, New York 2012

3. Your Faculty: Bennett Silver, M.D.
• Board Member, New Alliance Academy
• Medical Director, Adolescent PHP and
Consultation Liaison, St. Mary Hospital
• Board Certified Psychiatrist
• Editor Nationwide Newsletters
▫ Psychiatry Drug Alerts
▫ Child Psychiatry Drug Alerts
▫ Psychiatry NOS
▫ Readership over 22,000 psychiatrists

4. Conference Agenda
Dr. Gabriel Kaplan
• ADHD Epidemiologic and Diagnostic
Considerations
Dr. Bennett Silver
• Stimulants
Dr. Gabriel Kaplan
• Non Stimulants and New Approaches
Dr. Bennett Silver
• Non Medication Approaches

5. Epidemiological and Diagnostic
Considerations
Gabriel Kaplan, M.D.

6. Perceptions of ADHD: “Then” and “Now”
Then (20th
Century) Now (21st
Century)
Hill, Schoener. Am J Psychiatry. 1996;153(9):1143-1146. Klorman et al. J Am Acad Child Adolesc Psychiatry.
1987;26(3):363-367. J Am Acad Child Adolesc Psychiatry. 1991;30(3):I-III. Adler et al. J Atten Disord.
2008;11(6):720-727. Rostain. Postgrad Med. 2008;120(3):27-38. Weiss, J Clin Psychiatry. 2004;65(suppl
3):27-37. Barkley et al. J Abnorm Psychol. 2002;111(2):279-289.
Childhood disorder, remits in
adolescence
Functional impairment situational and
intermittent
70% persistence into adulthood
Core features
• Impairment of executive function
• Neurologically mediated (DA and
NE circuits)
Functional impairment continuous
across situations and throughout the day
Core features
• Impulsivity
• Hyperkinesis (restlessness)
• Attentional difficulties

7. Executive Functions
Frontal
Lobe
Perception
of
Time
Inhibit
Responses
Working
Memory
Internalize
Speech
Self
Regulation

8. ADHD DSM-IV-TR Criteria
Adapted from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC,
American Psychiatric Association, 2000.
A Either 1 or 2:
1. Six or more of a list of nine symptoms of inattention have been present for
at least 6 months, to a degree that is maladaptive
2. Six or more of a list of nine symptoms of hyperactivity-impulsivity have
been present for at least 6 months, to a degree that is maladaptive
B Some symptoms that cause impairment were present before age 7 years.
C Some impairment from the symptoms is present in two or more settings (e.g. at
school/work and at home).
D There must be clear evidence of significant impairment in social, school, or work
functioning.
E The symptoms are not better accounted for by another mental disorder

9. ADHD DSM-IV-TR Criteria
Inattention
(a) 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
(d) often does not follow through on instructions and fails to finish school work, chores, or duties in the workplace
(not due to oppositional behavior or failure to understand instructions)
(e) often has difficulty organizing tasks and activities
(f) often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork
or homework)
(g) 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
Hyperactivity -Impulsivity
(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 adolescents or adults, may
be limited to subjective feelings of restlessness)
(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"
(f) often talks excessively
(g) often blurts out answers before questions have been completed
(h) often has difficulty awaiting turn
(i) often interrupts or intrudes on others (e.g., butts into conversations or games)

10. Is ADHD Real?
• One of the most studied disorders of childhood with
several thousand publications in peer refereed journals
• Affects 5% to 8% of US children
• Statistics replicated throughout the world
• However, there is a small but vocal segment that insists
ADHD was invented by pharmaceutical companies to
sell drugs

11. Jan Steen - The Village School- 1665
Kast & Altschuler; The earliest example of the hyperactivity; 2008 South African medical journal

12. Jan Steen - The Village School - 1670

13. Sir Alexander Crichton (Scottish MD)
• In 1798 in the chapter of Attention in his book: An
inquiry into the nature and origin of mental
derangement
• Described a mental state with al the essential features of
the inattentive subtype of ADHD, the restlessness,
problems with attention, the early onset and how it can
affect the ability to perform in school.

14. ADHD is highly heritable
According to a metastudy by Faraone et al
in Biol Psych 2005;57:1313-1323, ADHD
mean heritability is 0.75 reaching almost
the heritability of height.

15. According to Shaw, Arch Gen
Psychiatry. 2006;63:540-549, cortical thickness in
ADHD compared with controls is significantly
thinner regions in the ADHD group.

16. Academic Impairment
• Very well documented
▫ Failure to perform academically is the single most common
source of referral for children and adolescents
• Children with ADHD
▫ Perform poorly on achievement tests and fail grades /
courses significantly more often than children without
ADHD
▫ Complete 3 fewer years of education than matched controls
▫ More likely not to graduate from high school (35%)
• Academic impairment more profound when learning
disabilities are present
Weiss & Hechtman Hyperactive Children Grown Up 1993
Manuzza & Klein The Economics of Neuroscience, 2001:47-53

17. Social Impairment
• Social problems begin in childhood, persist into
adolescence
▫ Fewer friends, more limited social skills
▫ Lower self esteem on assessment scores
▫ 3X’s as likely to have trouble getting along with peers
▫ ½ as likely to have good friends
▫ 2Xs as likely to get picked on by peers
▫ 3Xs as likely to have problems that limit after school
activities
Suppl. JAACAP Practice Parameters for Use of Stimulant Medications 2002;41:26S-49S
I.M.P.A.C.T. Survey;NYU Child Study Center;2001

18. Diagnostic Approach
• Despite significant advances in
anatomical/genetic research, there is NO current
validated biological marker
• Psychiatric interview and history remain the best
diagnostic tools
▫ Rule in (ADHD)
▫ Rule out (Mimics)

19. Rule in Approach
• Psychiatric Interview
▫ Family (family hx of ADHD)
▫ Child (school/social performance)
▫ Parents (marital/parental function)
• Collateral Information
▫ Rating Scales from Teacher (most reliable guide of
treatment progress)
▫ Discussion with teacher if available
▫ Discussion with grandparents if involved

20. Psychiatric Mimics of ADHD
Psychiatric Disorder Features Shared With ADHD Distinctive Features
Major depression •Impaired concentration
•Impaired attention/memory
•Difficulty with task completion
•Enduring dysphoric mood
•Anhedonia
•Appetite disturbance
Bipolar disorder •Hyperactivity
•Impaired attention/focus
•Mood swings
Enduring euphoric mood
•Insomnia
•Delusions
Substance abuse or dependence •Impaired concentration
•Impaired attention/memory
•Mood swings
•Pathologic patterns of
substance use (frequently with
social consequences)
•Physiologic tolerance/withdrawal
•Psychological
tolerance/withdrawal
Adapted from Searight et al. Am Fam Physician. 2000;62(9):2077-2086.

21. Medical Mimics of ADHD
• Thyroid disease
• Medication adverse effects
▫ Antiasthmatics
▫ Anticonvulsants
▫ Benzodiazepines
▫ Antihistamines
• Seizure disorder and other neurologic disorder
• Excessive caffeine consumption
• Sleep apnea
• Hearing impairment
• Chronic disease
Stein. CNS Spectr. 2008;13(10 suppl 15):14-16.

22. Differential Diagnosis Tools
• Physical Exam
▫ Specialists if necessary (Neurologist, Endochrinologist,etc)
• Rating Scales for current symptoms
▫ Conners’ ADHD Rating Scale
• Laboratory testing
▫ Chemistries (CBC, TFTs, etc)
▫ Sleep Lab
▫ EEG
• Psychological testing
▫ Not pathognomonic but helpful
Brown, ed. ADHD Comorbidities: Handbook for ADHD Complications in Children and Adults.
Washington, DC: American Psychiatric Press; 2009.

23. • Enhances signal
• Improves
attention
– Focus
– Vigilance
– Acquisition
– On-task behavior
– On-task cognition
Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
DopamineDopamine

24. Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
NorepinephrineNorepinephrine
• Dampens noise
• Decreases shifting
• Executive operations
• Increases inhibition
–Behavioral
–Cognitive
–Motoric

25. Trends in Prevalence of Stimulant Use
1987–2008
Zuvekas Am J Psychiatry. 2012;169(2):160-166
Since 1987, there has been a signficant
increase overall for ages 0-17. However, the
largest increase has been for ages 12-17 while
there was a decrease for ages 0-5.

26. Stimulant Treatment
Bennett Silver, MD

27. Societal and Workplace Impact of ADHD
• ADHD cost the U.S. economy between 143 billion and
266 billion in 2010
• That is roughly $2,000 per household
• Although commonly thought of as a childhood disorder,
adults with ADHD accounted for 73% of those estimated
costs
• The majority of these costs were the result of lost
productivity (62%), healthcare (26%), education (10%),
and the criminal justice system (2%)
• Effective treatment plans can improve the outcome of
ADHD and reduce these costs to society
*Congressional briefing on societal and workplace impact of untreated ADHD, November 30,2011

28. Stimulants
• Gold standard, first line treatment
• There are two chemical families with almost identical
therapeutic properties
▫ Amphetamines (AMPH)
▫ Methylphenidates (MPH)
• Amphetamines first used in 1937
• Stimulants are very effective (80%) and very safe.
• Only difference amongst multiple preparations is
duration of action

29. Short Acting Stimulants (up to 4hrs)
• MPH products
▫ Ritalin
▫ Methylin
▫ Focalin
• AMPH products
▫ Dexedrine
▫ Dextrostat
▫ Adderall

30. Long Acting Stimulants (More recently
approved)
• MPH products
▫ Oral (6-10 hrs)
 Methylphenidate-SR
 Ritalin (SR or LA)
 Methylin-ER
 Metadate (CD or ER)
 Concerta (8-10 hours)
 Focalin XR (8-10 hours)
▫ Patch (duration depends on length of time patch on)
 Daytrana
• AMPH products
 Adderall XR (8-10 hours)
 Vyvanse (at least 13 hours in children)

31. Choice of Stimulant
• It does not matter which MPH or AMPH starts first
• Most children will respond to one or the other
• If one is not effective or induces side effects, the child is
switched to the other one
▫ This strategy improves over 80% of patients
• Over 70% of psychiatrists prefer long acting
formulations
▫ Avoids having to see the nurse at noon
▫ Longer duration helps with homework
▫ Avoids rebound emotional lability as dose wears off

32. Stimulant Side Effects
• FREQUENT
▫ Decrease appetite
▫ Difficulty falling asleep
▫ Mood lability
▫ Stomach upset
▫ Dry Mouth
▫ Irritability
• INFREQUENT
▫ Clinically significant increased pulse or blood pressure
▫ Motor tics, Tourette’s
▫ Weight loss, slowed growth
▫ Psychosis
• Do not use in those with arrhythmias or other heart abnormalities
• Can be used as substance of abuse, to be avoided in active SA

33. Incomplete Diagnosis Can Lead to
Inadequate Treatment
• Sometimes ADHD is correctly diagnosed, appropriate
treatment and proper medication are initiated, but the
student only partially responds
• When this occurs it is necessary to look for co-existing
psychiatric disorders that may also require treatment
• As many as two thirds of children and adolescents with
ADHD have at least one other co-existing condition

34. ADHD and Co-Existing Disorders
• Learning Disabilities (30%-50%)
• Disruptive Behavior Disorders- ODD/CD (40%-50%)
• Depression (15%-30%)
• Bipolar Disorder (15%-20%)
• Anxiety (25%-30%)
• Substance Abuse (30%-35%)
• Sleep Disorders (30%-75%)

35. Is Substance Abuse More Common in Teenagers
Who Are or Were Treated with Stimulants?
• Youths with ADHD are at increased risk for substance
abuse; about one-and-a-half times greater risk than non-
ADHD youths*
• Current research documents that those adolescents with
ADHD prescribed stimulant medication are less likely to
subsequently use illegal drugs than are those not
prescribed medication **
*Wilens, T, et al. (2011). Does adhd predict substance-use disorders? A 10-Year follow-
up study of young adults with adhd. Journa of the American Academy of Child and
Adolescent Psychiatry 543-553: v50, i6
**Biederman, J, et al. (1999). Pharmacotherapy of attention deficit/hyperactivity
disorder reduces risk for substance use disorder. Pediatrics 104:e20

36. Non-Stimulants and New
Approaches
Gabriel Kaplan, MD

37. Stimulants vs. Non-Stimulants
• Stimulants strengths
▫ Act right away
▫ Very effective
▫ Gold standard
▫ Many preparations, multiple dosage strengths
▫ Well tolerated
• Stimulants weaknesses
▫ Controlled substances
▫ 20% non response
▫ Some patients do not tolerate AEs

38. When to use a Non Stimulant
• A Stimulant trial has failed
▫ Non effective or intolerable side effects
• Parents do not want to use a controlled
substance
• There is active drug abuse in the patient or
family
• There is a contraindication
▫ Sensitivity, heart problems
▫ Presence of Co-morbidities: ODD, Anxiety

39. Strattera
• Takes 3-4 weeks to work
• Selective Norepinephrine Reuptake Inhibitor SNRI (it
makes more NE available)
• Once per day dosage
• Although studies proved efficacy, in clinical practice,
physicians have been disappointed and is used less and
less often

40. Strattera Side Effects
• FREQUENT
▫ Upset stomach
▫ Decreased appetite
▫ Nausea or vomiting
▫ Dizziness
▫ Tiredness
▫ Irritability
▫ Insomnia
• INFREQUENT
▫ Liver failure
▫ Suicidal thoughts
▫ Urine retention
▫ Cardiac complications
▫ Psychosis

41. Intuniv
• Guanfacine Extended Release
• Approved 9/2009
• Acts on the same receptor as Norepinephrine (Selective
Alpha 2A)
• Its action, thus, mimics increased NE
• Taken once per day
• Takes a minimum of 2 weeks but most likely up to 4
weeks to work

42. Intuniv Side Effects
• FREQUENT
▫ Sedation
▫ Somnolence
▫ Fatigue
▫ Headache
▫ Increased appetite
• INFREQUENT
▫ Clinically significant low BP or heart rate
▫ Syncope
▫ Dizziness

43. Kapvay
• Clonidine Extended Release
• Approved 10/2010
• Acts on the same receptor as Norepinephrine (Alpha 2
non selective)
• Its action, thus, mimics increased NE
• Taken twice per day
• Takes a minimum of 2 weeks but most likely up to 4
weeks to work

44. Kapvay Side Effects
• FREQUENT
▫ Sedation
▫ Somnolence
▫ Fatigue
▫ Headache
▫ Increased appetite
• INFREQUENT
▫ Clinically significant low BP or heart rate
▫ Syncope
▫ Dizziness

45. How do you know the medication works
1. Executive Functions have improved
 Decreased impulsivity and motor behavior
 Increased attention
2. As shown by teacher reports (the most reliable
outcome measure)
 Via Rating scales: Conner's, etc or phone contact
with the provider directly or via parents
3. And there are no significant side effects

46. Newly Approved Combination Therapy
• Use a stimulant and a non stimulant at the same time
• Approved recently for Kapvay (2010) and Intuniv (2011)
but in use for decades with IR preparations
• For stimulant partial responders

47. Newly Approved Combination Therapy
• Stimulant Side Effects
▫ Anorexia
▫ Insomnia
▫ Hypertensive
• Non Stimulant Kapvay/Intuniv Side Effects
▫ Increased appetite
▫ Sedation
▫ Hypotension

48. Omega-3 fatty acid supplementation
improves ADHD
Bloch, JAACAP, 2011 50, 10:991-1000

49. Restriction Diet improves ADHD
Nigg JAACAP 51:1; 2012

50. Non- Medication Approaches
Bennett Silver, MD

52. Despite the Well Documented Benefits of
Medication for ADHD
• As many as 20% of children with ADHD derive
inadequate benefit from medication
• Side effects prevent some from receiving medication on
an extended basis
• Even those who benefit from medication may still have
difficulties with primary ADHD symptoms or associated
problems which must be targeted via other means
• Mild ADHD may be managed without medication
• Some parents and teens will refuse medication

53. A Cognitive-Behavioral Model of Impairment in ADHD
Mood
Disturbance:
•Depression
•Guilt
•Anxiety
•Anger
Failure to Utilize
Compensatory
Strategies-examples:
•Organizing
•Planning (i.e. task list)
•Managing
Procrastination
Avoidance
distractibility
Core
(Neuropsychiatric)
Impairments in
•Attention
•Inhibition
•Self-Regulation
(impulsivity)
History of:
•Failure
•Underachievement
• Relationship Problems
Dysfunctional
Cognitions and Beliefs
(“I can’t do it.”)
(“I am a loser.”)
Functional
Impairment

54. Behavior Therapy Based on Principles About
What Leads Children to Behave Appropriately
• Children want to please their parents and feel good
about themselves when their parent is proud of them
• Children behave appropriately to obtain positive
consequences (privileges/rewards)
• Children want to avoid negative consequences that
follow inappropriate behavior

55. Behavior Therapy Core Concept
• Increase the frequency of desirable behavior with
positive consequences for good behavior
• Reduce inappropriate behavior with negative
consequences for bad behavior

56. • Be very clear about what behavior is expected of the
student in order to earn a reward
• “Listen to what I say” is too vague
• “Take your seat without talking the first time I ask you
to do so” is more specific
PositivePositive Reinforcement Basic Principles 1

57. PositivePositive Reinforcement Basic Principles 2
• Make sure that the expectations you have for a student
are reasonable – do not set the student up for failure
with expectations that are not appropriate for his/her
abilities
• This includes in class activities as well as homework
assignments

58. PositivePositive Reinforcement Basic Principles 3
• Don’t try to work on too many different things at one
time
• It is better to concentrate on a few things that are very
important rather than taking on too much at once –
choose your battles carefully!

59. PositivePositive Reinforcement Basic Principles 4
• Let the student participate in the type of rewards he or
she can earn – they will be more invested in a program
when they have input into its design. Let it be something
you are doing with them rather than to them
• Design the program so that there is a good chance to
experience initial success – this will enhance motivation
and you can gradually raise the bar

60. PositivePositive Reinforcement Basic Principles 5
• Provide many social rewards (praise) in addition to
tangible rewards that can be earned – this will increase
the student’s desire to please you and generate positive
feelings between you
• Be consistent – apply the program daily and always
provide rewards when they are earned

61. NegativeNegative Reinforcement Basic Principles
• When a negative behavior is consistently followed by
negative consequences that behavior should diminish in
frequency and intensity
• The punishment for specified bad behaviors is clear –
e.g., time-out, loss of privilege, loss of points or tokens
• The student will understand that there is simply no pay-
off for bad behavior

62. NegativeNegative Reinforcement Basic Principles
(Cont.)
• Try not to overdo the negative consequences
• Students get discouraged and lose interest in the
program if they are used too frequently
• Resorting to negative consequences too often means you
should re-evaluate your program and possibly redesign it
• Utilize a pre-planned graded series of punishments for
persistent misbehavior

63. Modifications to a Behavioral Program
Specific to an ADHD Student
• Give more frequent feedback to the student about how
they are meeting teacher expectations – e.g., hourly
instead of daily
• Utilize short term goals, with shorter intervals between
the opportunity to earn rewards – points or tokens are
especially helpful
• More frequent reminders about expectations and what
can be earned by good behavior
• Frequent changes in the program to sustain interest in it

64. Integrated Model for Optimal Treatment of ADHD