Educational Objectives

After completing this activity, the participant should be better able to:

• Explain how the proper recognition and management of ADHD in

adolescents by MCOs can improve clinical outcomes and reduce the
economic burden of disease
• Indicate the link between ADHD and the most common psychiatric
comorbidities
• Describe current ADHD guidelines and treatment protocols
• Outline opportunities to maximize health plan performance for the
ADHD HEDIS measure
• State examples of ADHD quality improvement strategies for MCOs

Effectively Recognizing and Managing

ADHD in Adolescents

Timothy E. Wilens, M.D

Clinical & Research Program in Pediatric Psychopharmacology
Massachusetts General Hospital
Harvard Medical School

1
 Overview

• Estimated prevalence:
– 6 to 8% of children
– 6% of adolescents
– 4% of adults
• 4:1 male to female ratio in children and adolescents
• Treatment utilization varies widely within and between cultures,
ethnicities, and socioeconomic status

Goldman LS, et al. JAMA 1998;279:1100-1107.

Barkley RA. In: Mash EJ, Barkley RA. eds. Treatment of Childhood Disorders. New York; Guildford Press 1989.

ADHD Subtypes

• DSM-IV-TR* ADHD subtypes

– Combined subtype (50–75%)
– Primarily inattentive (20–30%)
• Increases with age
– Primarily hyperactive–impulsive (<15%)

*DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition, Text Revision. Washington, DC. American
Psychiatric Association. 2000;48:85-93.

Etiology

• ADHD is a heterogeneous behavioral disorder with multiple

possible etiologies

Neuroanatomic Genetic
Neurochemical origins

ADHD

Environmental
CNS insults
factors

Biederman J, Faraone SV. Lancet 2005;336:237-48.

2
 DSM-IV Diagnostic Criteria for ADHD

1. Either (1) Symptoms of inattention, or (2) symptoms of

hyperactivity-impulsivity or (3) both
2. Onset <7 years of age (childhood-onset)
3. >6 months of disturbance
4. Cross-situational (home, work, school)
5. Impairment in functioning

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition, Text Revision. Washington, DC. American
Psychiatric Association. 2000;48:85-93.

Clinical Presentation in an Adolescent

(13-18 Years of Age)

• May seem restless rather than hyperactive

• Problems with attention, task completion, shifting of activities
prematurely
• School work disorganized and shows poor follow-through; fails
to work independently
• Seems emotionally immature
• Has poor self-esteem
• Has poor peer relationships
• May engage in irresponsible or risky behavior

Wolraich ML, et al. Pediatrics. 2005;115:1734-1746.

Barkley RA. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 3rd ed. New York, NY: Guilford Press; 2006.
Barkley RA, et al. J Am Acad Child Adolesc Psychiatry. 1991;30:752-761.

ADHD Developmental Trends by Age

• Symptoms of ADHD decline and change from childhood to

adulthood

Children Motoric hyperactivity

Low frustration tolerance
Impulsiveness
Distractibility
Shifting of activities
Fidgetiness
Impatience
Restlessness
Inattentiveness
Adults
Wolraich et al. Pediatrics. 2005;115:1734-1746.
Millstein et al. J Attention Disorder 1997.

3
 Evidence of Persistence of ADHD Into
Adulthood

80 72
65 66
58
Percentage

60

40 31

20

0
1 2 3 4 5*
Age at
6 to 17 4 to 12 6 to 12 6 to 12 6 to 18
diagnosis

Age at follow-
10 to 21 12 to 20 16 to 23 21 to 33 16 to 28
up

*Same cohort as study 1 at 10-year follow-up.

Biederman J, et al. Arch Gen Psychiatry. 1996;53:437-446.
Barkley RA, et al. J Am Acad Child Adolesc Psychiatry. 1990;29:546-557.
Gittelman R, et al. Arch Gen Psychiatry. 1985;42:937-947.
Weiss G, et al. J Am Acad Child Psychiatry. 1985;24:211-220.
Biederman J, et al. Psychol Med. 2006;36;167-179.

Common Co-occurring Conditions

• Oppositional defiant disorder (ODD)

• Conduct disorder (CD)
• Anxiety disorders
– Generalized anxiety disorder
– Obsessive-compulsive disorder (OCD)
– Posttraumatic stress disorder (PTSD)
• Depression
• Bipolar disorder
• Tic disorder
• Learning disabilities

Cumulative Morbidity Risks for Psychiatric

Disorders in Young Men With ADHD

1
Cumulative morbidity risk

ADHD
0.8 Control *

0.6
* *
0.4
*
*
0.2 †

0
MDD BPD OCD Tic ODD CD
disorders
*ADHD vs Control, P<.001
†P = .004

10-year follow-up of males with ADHD (n = 112) and case controls (n = 105)
Mean age at follow-up: 22 years
MDD = major depressive disorder; BPD = bipolar disorder; OCD = obsessive-compulsive disorder;
ODD = oppositional defiant disorder; CD = conduct disorder.
Biederman J, et al. Psychol Med. 2006;36:167-179.

4
 Academic and Behavioral Impairments
Continue in Adolescence

• 15–25% of children have poor academic outcome1–5

• Almost 30% of ADHD subjects fail grades2
• 46% of ADHD pupils suspended2
• 25% of persistently antisocial6–9

1. Gittelman R, et al. Arch Gen Psychiatry. 1985;42:937-947.

2. Barkley RA. Attention-Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment, 2nd ed. New York: Guilford Press;1998.
3. Mannuzza S, et al. J Am Acad Child Adolesc Psychiatry. 1997;36:1222-1227.
4. Mannuzza S, et al. Arch Gen Psychiatry. 1993;50:565-576.
5. Weiss G, Hechtman L. Hyperactive Children Grown Up. 2nd ed. New York: Guilford Press 1993.
6. Mannuzza S, et al. Arch Gen Psychiatry. 1989;46:1073-1079.
7. Mannuzza S and Klein RG. Child Adolesc Psychiatr Clin N Am. 2000;9:711-726.
8. Barkley RA. Attention-Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment, 2nd ed. New York: Guilford Press;1998.
9. Fischer M, et al. J Abnorm Child Psychol. 2002;30(5):463-475.

ADHD Adolescents and Driving

License suspended

Speeding violations

Other traffic violations

Accidents

Fault

Injuries

More damage

0 2 4 6 8
Increased likelihood of outcome compared with
age-matched controls
Barkley RA, et al. Pediatrics. 1993;92:212-218.
Cox D, et al. J Nerv Ment Dis. 2000;188;230-234.
Barkley RA, et al. Pediatrics. 1996;98:1089-1095.
Murphy K, Barkley RA. Comp Psychiatry. 1996;37:393-401.

ADHD: Risk of Substance Abuse

Sharp rise in Substance Abuse between

mid-adolescence and adulthood
60% 55%

50%
Control
Percent Increase in Risk

ADHD
40%

30% 27%

20% 15% 15%

10%

0%
Youth Adults

Biederman J, et al. J Am Acad Child Adolesc Psychiatry. 1997;36:21-29.

Biederman J, et al. Am J Psychiatry. 1995;152:1652-1658.
Wilens TE, et al. J Nerv Ment Disord. 1997;185:475-482.

5
 Sexual Behavior

Casual sex past year P = 0.01

Casual sex + infrequent condom use P = 0.02

>4 sex partners (lifetime)

P <0.001

Pregnancy P <0.001

0 10 20 30 40 50 60 70
Participants (%)
Control (n = 111) ADHD (n = 175)

Young men (aged 18–26) with and without childhood ADHD; self-reports
Flory K, et al. J Clin Child Adolesc Psychology. 2006;35:571-577.

Criminality

100
P <0.001
ADHD Control
80 P = 0.001
Participants (%)

60 P = 0.019

P <0.001 P <0.001
40
P = 0.025 P = 0.006
P = 0.005
20

0
Stolen Assault with Assault with Carried Ever arrested Arrested Misdemeanor Felony arrest
property fists weapon concealed twice or more arrest
weapon

ADHD: n = 147; 87% Male; mean age = 21.1

Control: n = 73; 92% Male; mean age = 20.5
Barkley RA, et al. J Child Psychol Psychiatry 2004;45:195-211.

Neurobiology of ADHD

• Smaller frontal lobes, basal ganglia, cerebellar vermus

• Delay in white matter/frontal tract maturation
• Abnormal PET and fMRI studies (multiple)
• Abnormal DAT binding
• Abnormal dopamine transmission
• Genetic studies (multiple)
– Twin > 0.80 concordance
– Candidate genes (D4, D2, DAT, SNAP, 5HT)

PET: Positron Emission Tomography; fMRI: Functional magnetic resonance imaging; DAT: Dopamine transporter; SNAP: S-
nitroso-N-acetylpenicillamine; 5HT: 5-hydroxytryptamine

Faraone SV, et al. Am J Psych 1999;156:768-70.

Zametkin AJ, Liotta W. J Clin Psych 1998;59 Suppl 7:17-23.
Ernst M, et al. Am J Psychiatry. 1999;156:1209-15.
Casetellanos FX, et al. JAMA 2002;288:1740-8.
Faraone SV, et al. Biol Psychiatry. 2005;57:1313-23.

6
 Treatment Considerations in
Adolescents with ADHD

• Psychoeducation
• Educational intervention/remediation
• Counseling
• Supportive problem-directed therapy
• Cognitive/behavioral intervention
• Coaching
• Family therapy
• Medication

Wolraich et al. Pediatrics 2005:115:1734-46.

Treatment Considerations for

Adolescents With ADHD

Adolescents are neither children nor adults

• Adolescents often need to feel “in control” of condition and
treatment
– Problems negotiating treatment alliance
– Adherence
• In selecting medication
– Tailor treatment to fit adolescent’s schedule
– Keep treatment private/out of school
– Consider and discuss risk for substance abuse, misuse, and diversion

Wolraich et al. Pediatrics 2005:115:1734-46.

Pharmacologic Treatments Approved

for ADHD
Methylphenidate-based formulations Duration of effect
Methylprenidate (Concerta®) ~12 hours
Methylprenidate (Ritalin®) 3–4 hours
Methylprenidate (Metadate® CD) 8–10 hours
Methylprenidate (Ritalin® LA) ~8 hours
Dexmethylphenidate (Focalin® XR) 3–4 (8–10) hours
Methylphenidate (Daytrana®) ~12 hours (worn for 9)
Amphetamine-based treatments
Mixed amphetamine salts (Adderall XR®) 10–12 hours
Mixed amphetamine salts (Adderall®) 4–6 hours
Dextroamphetamine (Dexedrine® Spansule) 6–8 hours
Lisdexamfetamine dimesylate (Vyvanse®) 12 hours
Nonstimulant
Atomoxetine (Strattera®) Up to 24 hours

Physicians’ Desk Reference. 59th ed. Montvale, NJ: Thomson PDR; 2005.

7
 Dosing Stimulants

• Start with low dose to establish tolerability

• Titrate until no further improvement is seen or until significant
side effects are noted
• Underdosing is a common concern (methylphenidate)
• No simple association between optimal dosage and age,
weight, or blood levels, although adolescents and adults
usually require a higher dose than do children
• If an effective medication seems to become less effective as a
child reaches adolescence, try increasing the dose

Potential for Abuse

• Nonstimulants (eg, atomoxetine, bupropion) are less likely to

be misused or diverted than stimulants
• The slower the uptake into the brain, the lower the abuse
liability of the stimulant
• Long-acting formulations of stimulants are less likely to be
misused or diverted than immediate-release formulations

Volkow ND, et al. Nature 1997;386:827-830.

Spencer TJ, et al. Am J Psychiatry. 2006;163:387-395.

ADHD and Substance Abuse

Survival Curve: Risk for Substance Use Disorder (SUD)
Onset in Adults With Untreated ADHD
100
ADHD
90
Control
80
Risk for SUD (%)

70
60
P ≤0.05, ADHD vs
50
control at endpoint
40 Earlier onset
30
20
10 Higher risk
0
0 10 20 30 40 50 60
Age at onset (years)
Wilens T, et al. J Nerv Ment Dis. 1997;185:475-482.

8
 Pharmacotherapy and Substance
Abuse With Stimulants

• Fear: Stimulant therapy may lead to substance abuse

• Fact: Untreated ADHD is a significant risk factor for substance
abuse in adolescence

Pharmacotherapy for ADHD

may be protective against
substance abuse

Biederman J, et al. Pediatrics. 1999;104:20; Wilens et al. Pediatrics. 2003;11:179-183.

Faraone SV, Wilens T. J Clin Psychiatry. 2003;64(suppl 11):9-13.

Misuse and Diversion of Stimulants

Adolescents with ADHD are more likely to misuse or divert their

medication than are non-ADHD adolescents taking psychoactive drugs

5%
Misused
22%

5% No ADHD (n = 43)
Got high
10%
ADHD (n = 55)
5%
Used too much
22%

0%
Sold
11%

0% 5% 10% 15% 20% 25%

Patients

Wilens T, et al. J Am Acad Child Adolesc Psychiatry. 2006;45:408-414.

Characteristics of ADHD Patients Who

Misuse or Divert Medication
ADHD patients with comorbid CD or SUD are
more likely to misuse or divert their medication.

53% SUD
All ADHD
(N = 55)
31% CD

75%
Misuse
(n = 12)
58%

83%
Divert
(n = 6) 83%

0% 20% 40% 60% 80% 100%

Patients
Wilens T, et al. J Am Acad Child Adolesc Psychiatry. 2006;45:408-414.

9
 Possible Predictors of Misuse of ADHD
Medications

• Signals alerting to the possible motivation to misuse ADHD

agents include
– Competitiveness of the college environment1
– Other drug use2
– Presence of:
• Current ADHD and depressive symptoms3,4,5
• Neuropsychological deficits5

1. McCabe SE, et al. Addict Behav 2005;30:1342-50.

2. White BP et al. J Am Coll Health 2006;54:261-8.
3. Poulin C. Addiction 2007;102:740-51.
4. Upadhyaya HP, et al. J Child Adolesc Psychopharmacol 2005 ;15 :799-809.
5. Wiens TE, et al. J Am Acad Child Adolesc Psychiatry 2008: In press.

OROS MPH (90 mg) & IR MPH (40 mg):

“Feel an Effect”

25

20 IR-MPH
OROS-MPH
Feel an Effect

15
*
10 * †
*
*
5

0
0 1 2 3 4 5 6 7 8 9 10

N=6 per group.

Time (hrs)
*p < 0.05.
†
p < 0.01.
IR: extended release; OROS = osmotically controlled-release oral delivery system
Spencer TJ, et al. Am J Psychiatry. 2006;163:387-395.

Does Stimulant Treatment Effect Neural Activity?

• ADHD associated with dysfunction of the dorsal anterior

midcingulate cortex (daMCC) and other
cingulofrontoparietal regions associated with attention
• Stimulants are effective therapy for ADHD
• Study conducted to determine if stimulant treatment
effects neural activity
• daMCC activation during the Multi-Source Interference Task
measured by functional MRI (fMRI) in 21 adults with ADHD
treated for 6 weeks
• MPH OROS (n=11)
• Placebo (n=10)

Bush G, et al. Arch Gen Psychiatry. 2008;65:102-114.

10
 Treatment with OROS MPH Increased Activation in
Regions Associated with Attention

• MPH OROS treatment

elicited increased
activation of the
cingulofrontoparietal
network including:
• Dorsal anterior
midcingulate cortex
(daMCC) bilaterally
• Right-sided dorsolateral
prefrontal cortex (DLPFC)
• Bilateral superior parietal
cortices (Parietal)

Sagittal Axial Coronal

Bush G, et al. Arch Gen Psychiatry. 2008;65:102-114.

ADHD Treatment Summary

In Adolescents

• Methylphenidate, mixed amphetamine salts, and atomoxetine

are all safe and efficacious in adolescents with ADHD
• MPH has the most clinical trial data
• Long-acting forms of methylphenidate and mixed
amphetamine salts are also safe and effective and are thought
to have a lower risk of abuse compared to immediate-release
forms
• Atomoxetine is the only FDA-approved nonstimulant for ADHD

Treatment Plan (continued)

• Management of comorbid disorders

– Psychotherapy
– Medication
– Substance abuse treatment programs
• Assistance with time management and organization (consult
ADHD coaches or therapists)
• Psychosocial treatments
– Family therapy or parent management training
– Individual therapy
• Vocational assessment/career counseling

11
 Adolescent ADHD Summary

• ADHD is frequently persistent into adolescence

• Common domains of impairment
– Academic underachievement
– Family functioning
– Driving
• Adolescents with ADHD respond favorably to treatment
• Medication is fundamental to treatment
• Medications in ADHD
– Improve ADHD symptoms
– Improve functional outcomes (family, driving, social)
– Reduce risk for substance abuse
– Permit many to succeed and go to college

Managed Care Strategies to Improve

ADHD Outcomes

Jeffrey D. Dunn, PharmD, MBA

Formulary and Contract Manager
SelectHealth Plans
(formerly IHC Health Plans, Inc.)

ADHD is a Common Diagnoses in

Children Less Than 18 Years Old

2006 National Health Interview Survey

20% Asthma
0.14
15%
years old with diagnosis

0.12
Percent of children <18

Respiratory
10% 0.08 0.07 Allergy
Learning
5%
Disability
0% ADHD
a

HD
y
rg
m

t
ili
th

D
lle

ab

A
As

is
ry

D
to

gn
ra

ni
pi

ar
es

(n=73,493) (n=61,354)
Le
R

(n=73,493) (n=61,354)

Bloom B, Cohen RA. Vital Health Stat 10. 2007;234:1-79.

12
 Consequences of Untreated ADHD
Increase with Age

• Antisocial
Behavior
• School
• Disruptive • Oppositional Exclusion
Behavior Defiant • Substance
• Poor Disorder Abuse
• Low
• ADHD only Social • Mood • Conduct
Self-
Skills Disorder Disorder
Esteem
• Learning • Challenging • Lack of
Delay Behavior Motivation
• Complex
Learning
Disorder

Age (years) 6 10 14-16

Kewley GD. Attention Deficit Hyperactivity Disorder (ADHD): Recognition,Reality and Resolution. Oxon, United Kingdom: David Fulton
Publishers;2002.

Impact of ADHD in Childhood and

Adolescence Compared to non-ADHD Peers

Society
Health Care Use
2X > Risk for SUD6
50% ↑ Bicycle accidents1
Earlier onset of SUD7
33% ↑ Emergency visits2
More likely to continue
>4x ↑ Vehicle accidents3
SUD into adulthood8

School/Work Family
46% Expelled4 >4x h Sibling fighting9
35% Dropped out4 >4x h Separation/divorce
Lower occupational status5 in adulthood10

6. Biederman J, et al. J Am Acad Child Adolesc Psychiatry

1. DiScala C, et al. Pediatrics 1998102:1415-21 . 1997;36:21-29.
2. Liebson CL, et al. JAMA 2001;285-60-66. 7. Pomerleau OF, et al. J Subst Abuse 1995;7:373-8.
3. Barkley RA, et al. Pediatrics 1996;98:1089-1095. 8. Wilens T, et al. Psychiatr Serv 1995;46:761-3, 765.
4. Barkley RA, et al. J Am Acad Child Adolesc Psychiatry 1990;29:546-557. 9. Mash EJ, Johnston C. J Consult Clin Psychol 1983;51:86-99.
5. Mannuzza S, et al. J Am Acad Child Adolesc Psychiatry 1997;36:1222-1227. 10. Barkley RA, et al. J Child Psychol Psychiatry 1991;32:233-55.

ADHD Associated with Lower Educational

Achievement and Income

Fulltime Employed by Average Income by

Academic Achievement 100,000
Academic Achievement
100% **
91.3K
†
† 77% 80,000
72%
75%
†
65% 63.0K
66.6K
56% 55% 60,000
52.4K
*
46.7K
50%
† 38.7K
34% 40,000
30% 29.5K
22% 23.8K
25%
20,000

0% 0
Less than High College; Post-grad Less than High College; Post-grad
high school; some post degree high school; some post degree
school some grad school some grad
college ADHD (n=500) college
No ADHD (n=501)
†
p<.001 for all comparisons. *p<.05; **p<001.
Biederman J, Faraone SV. MedGenMed. 2006;8:12.

13
 ADHD Associated with Greater Use of
Hospital Care
Population based Cohort Study of Adolescents
(Mean Age: 15.3 years)
100% p=.005
ADHD
81%
No ADHD
Proportion requiring

74%
hospital services

75% n=4119
p=.006

50% p<.001 41%

33%
26%
25% 18%

0%
In-patient Care Out-patient Care ED Admission
Leibson CL, et al. JAMA 2001;285:60-66.

Presence of ADHD Increases Health

Care Utilization Costs
Patients 3-17 Years of Age Enrolled in the Group Health Cooperative

$1,500 No ADHD $1,465*

(n=11,968)
Costs per patient per year

$1,200 ADHD (n=2,992)

*p <0.001 vs. no ADHD

$900
$690
$600
$427*
$335*
$245 $222*
$300
$20 $66
$0
Primary Care Mental Pharmacy Total
Health Care

Guevara J, et al. Pediatrics 2001;108:71-78.

ADHD Diagnostic and Treatment

Guidelines
Organizations with ADHD Practice Guidelines

AAP
Practice Guideline
May 2000

AACAP Practice Parameters NIH Consensus Statement

October 1997 February 2000

AAP: American Academy of Pediatricians

AACAP: American Academy of Child and Adolescent Psychiatry
NIH: National Institutes of Health

14
 Are Providers Using the Guidelines?

• Survey of 1374 physicians indicated

– 92% of pediatricians and 60% of primary care physicians were familiar with the
AAP guidelines
– Only 26% used all 4 diagnostic components in the guidelines
• DSM criteria
• Parent surveys
• Teacher surveys
• Assessment for co-existing conditions

Rushton JL, et al. Pediatrics 2004;114:e23-e28.

Approach to ADHD Treatment

• ADHD is highly treatable1

– Combination of behavioral and pharmacological approaches most effective to
control symptoms1
• Stimulants remain 1st line treatment1
– Any individual stimulant effective in ~70% of ADHD patients2
– Many who fail to respond to one may respond to another2,3
• Stimulants generally safe and well tolerated3
• Non-stimulating agents recently introduced

1. American Academy of Pediatrics. Pediatrics. 2001;1081033-44.

2. US Department of Health and Human Services, 1999.
3. Scott-Levin Inc., Physician Drug and Diagnosis Audit (PDDA), 2001.

American Academy of Pediatrics (AAP):

ADHD Treatment Goals

• Immediate and long-term control of symptoms

• Decreased disruptive behaviors
• Improved academic performance
• Increased independence
• Improved self-esteem
• Improvements in relationships

American Academy of Pediatrics. Pediatrics. 2001;1081033-44.

15
 AAP Treatment Plan

• Begin patient and family education about ADHD immediately

after diagnosis
• Implement home, work, school, and lifestyle adjustments
• Initiate therapy with appropriate medication targeting
symptoms
• Identify and manage comorbid conditions
– Psychotherapy or cognitive therapy
– Substance abuse treatment

American Academy of Pediatrics. Pediatrics. 2001;1081033-44.

Pharmacologic Intervention in ADHD

Stimulants
Methylphenidate Amphetamine

Short Acting Intermediate Long Acting Short Acting Intermediate Long Acting
SODAS MPH MPH SR OROS MPH Dextroamphetamine Dextroamphetamine ER MAS XR
Dexmethylphenidate MPH SR Diffucaps MPH Dextroamphetamine tabs MAS
MPH LA
Dexmethylphenidate XR
MPH transdermal patch

Nonstimulant

Approved Not Approved

Atomoxetine TCA
Modafinil; Bupropion
Guanfacine; Clonidine
Venlafaxine

SODAS = spheroidal oral drug absorption system; MPH = methylphenidate; SR = sustained release;
ER = extended release; OROS = osmotically controlled-release oral delivery system; LA = long acting;
XR = extended release; TCA = tricyclic antidepressants

Drug Therapy of ADHD is Highly

Cost-Effective

• For the routine treatment

of children with ADHD,
medication management
is more cost-effective
than behavioral treatment
or combined medication +
behavioral therapy*

*From the Multimodal Treatment

Study of Children with ADHD
(n=579 children 7-9.9 years of age
treated for 14 months)

Jensen PS, et al. Am J Psychiatry 2005;162:1628-1636.

16
 Managed Care Considerations with
ADHD Therapy

• Dosing flexibility and convenience

• Duration of action
– Short- vs. long-acting agents
• Risk for abuse or diversion
• Tolerability and safety
• Cost
• Access/reimbursement
• Pediatric vs. adult
• Polypharmacy
• Formulary management
– DACON, future generics, new products

Considerations for Stimulants

• Stimulant usually chosen for most children and teens

– Efficacy supported by over 200 randomized, placebo-controlled, blinded clinical
trials
– Most studies of short duration (i.e., 2-4 months)
– Few long term trials
• MPH and DEX have similar profiles
– DEX slightly more side effects, which are mild
– Mixed amphetamine salt preparation (Adderall)
• Recent withdrawal of long acting product in Canada
• Warning of use in children with cardiac conditions
• Selective nature of stimulants can vary from one agent to
another
• Consider parent preference

First Line Therapy

• Stimulants recommended as first line therapies

– Efficacy ranges from 68-80%
– 3-4% of patients experience side effects causing discontinuation
– Many generics available in the short-acting formulation
• Long-acting generics are not yet available
– Duration of effect ranges from 2-12 hours

American Academy of Pediatrics. Pediatrics. 2001;1081033-44.

17
 Second and Third Line Interventions

• Atomoxetine second line

– Effective in 50 – 60% of patients
– Similar side effects to stimulants
– Provides 24 hour coverage
– 1-3 weeks to reach effect
• Bupropion
– Fewer studies, more serious side effects
– Role of antidepressant effect
– 24 hour coverage with twice daily dosing
– 3-4 weeks to reach effect

American Academy of Pediatrics. Pediatrics. 2001;1081033-44.

Newer ADHD Pharmacotherapies

Duration of Dosing Schedule

effect
MPH Formulations
• Methylprenidate (Concerta®) 12 hours Once daily
• Methylprenidate (Metadate® CD) 8-10 hours Once daily
• Methylprenidate (Ritalin® LA) ~8 hours Once daily
• Dexmethylphenidate [(Focalin® (XR)] ~5 (10) hours Twice (once) daily
• Methylprenidate (Daytrana®) 7-12+ hours Once daily
Amphetamine Formulations
• Mixed amphetamine salts (Adderall® XR) 12 hours Once daily
• Dextroamphetamine (Dexedrine Spansules®) ~4 (8) hours Multiple
• Mixed amphetamine salts (Adderall®) 6-8 hours Twice daily
• Lisdexamfetamine dimesylate (Vyvanse®) 12 hours Once daily
Non-Stimulants
• Atomoxetine (Strattera®) 8-24 hours Once/twice daily

ADHD Drug Dosing

Starting Maximum Dosing

Medication
Dose Dose Schedule
Methylprenidate (Ritalin) 5 mg 60 mg TID
Dexmethylphenidate (Focalin) 2.5 mg 10 mg BID
Methylprenidate (Concerta) 18 mg 72 mg QD
Methylprenidate (Metadate CD) 20 mg 60 mg QD
Methylprenidate (Ritalin LA) 10 mg 60 mg QD
Dexmethylphenidate (Focalin XR) 5 mg 20 mg QD
Methylprenidate (Daytrana) 10 mg 30 mg QD
Mixed amphetamine salts (Adderall) 2.5 to 5 mg 40 mg BID
Mixed amphetamine salts (Adderall XR) 5 to 10 mg 30 mg QD

Dextroamphetamine (Dexedrine) 2.5 to 5 mg 40 mg BID/TID

Dextroamphetamine (Dexedrine Spansules) 5 mg 50 mg BID
Lisdexamfetamine dimesylate (Vyvanse) 30 mg 70mg QD
Atomoxetine (Strattera) 40mg 100 mg QD/BID
Wilens TE, et al. Ann Rev Med. 2002;53:113-131.

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 Drug Delivery Systems May Reduce
Risk for Abuse and Diversion

• Newer delivery systems may reduce misuse liability

• Different formulations alter pharmacokinetics and/or limit
access to the active drug by using
– Prodrugs [lisdexamfetamine dimesylate (Vyvanse)]
– Beaded preparations [methylprenidate (Adderall XR; Ritalin LA);
dexmethylphenidate (Focalin XR)]
– Osmotic preparations [methylprenidate (Concerta; Metadate CD)]
– Transdermal delivery systems [methylprenidate (Daytrana)]

Volkow ND, et al. Nature 1997;386:827-830.

Spencer TJ, et al. Am J Psychiatry. 2006;163:387-395.

Pharmacy Management Issues in the

Treatment of ADHD

• Polypharmacy
– Combination of long-acting agents
– Combination of short-acting agents
– Use with modafinil (Provigil), sedative hypnotics, etc.
– Different doctors
• Suboptimal dosing
– High DACON
• Appropriate use vs. potential for abuse
• Off-label use

Recommendations for Managing

Polypharmacy

• Polypharmacy
– Limit to one long-acting agent at one time (a short-acting in combination could be
allowed)
• Methylprenidate (Concerta; Adderall XR) would not be allowed at the same
time
– Limit to one short-acting agent at one time (a long-acting in combination could be
allowed)
• MPH IR and mixed amphetamine salts would not be allowed at the same time
• Dose optimization
– Methylprenidate (Concerta) 18 mg bid → methylprenidate (Concerta) 36 mg qd or
methylprenidate (Concerta) 18 mg qd + MPH IR qd
• Quantity limits
– One long-acting agent per day

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 Improving Adherence to Treatment

• 48% of patients 9-15 years of age discontinued therapy over 3

year period1
• Strategies to improve adherence2
• Educate patients and parents regarding anticipated results,
benefits and possible adverse events
– Provide frequent follow-up early in treatment
– Strive for dose optimization
– Identify and treat comorbid conditions
• Dose response vs. titration
– Dosing needs to increase when patients get older and their weight increases

1. Wolraith EL, et al. Pediatrics. 2005;115:1734-46.

2. Grcevich S, et al. Presented at: The 53rd Annual Meeting of the American Academy of Child and Adolescent Psychiatry; October 2006, San Diego,
CA.

Patient Monitoring Recommended Every

3-4 Months

• Optimal frequency of follow up is not well studied

• If intervals longer than 4 months
– Potential for medication to be continued even if its not effective
– Potential for medication to be prematurely discontinued or switched to another with
greater potential for side effects

American Academy of Childhood and Adolescent Psychiatry. J Am Acad Child Adolsec Psychiatry 2007;46:894-921.

Monitoring for Adverse Events

• At all visits, patients should be monitored for

– Appetite, headache, abdominal pain, sleep, emergence of tics, mood changes,
irritability
• “Rebound” phenomena
• Most side effects are responsive to changes in dose or timing

American Academy of Childhood and Adolescent Psychiatry. J Am Acad Child Adolsec Psychiatry 2007;46:894-921.

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 HEDIS ADHD Measure

• Recently developed HEDIS measure for ADHD assesses

follow-up care for children (6-12 years) prescribed ADHD
therapy
• Initiation Phase Management
– Percentage of children with a prescription for ADHD medication who had one
follow-up visit with a practitioner during the 30-day Initiation Phase
• Continuation and Maintenance
– Percentage of children with a prescription for ADHD medication, who remained on
the medication for at least 210 days and had at least two follow-up visits in the nine
months after the end of the Initiation Phase

National Committee for Quality Assurance. The state of health care quality: Industry trends and analysis. Washington, DC. 2007.

Achievement of the HEDIS ADHD Measure

Percent of Commercial Plans Achieving the

ADHD Initiation Phase Performance Measure
40%

32% 33%

30%
Percent of Plans

20%

10%

0%
2005 2006
National Committee for Quality Assurance. The state of health care quality: Industry trends and analysis. Washington, DC. 2007.

Achieving the HEDIS ADHD

Performance Measure

• Steps to improve performance on the HEDIS ADHD measure

include
– Education and implementation of evidence-based care
– Registry of patients with current ADHD diagnosis to allow for long-term follow up
– Implementation of drug therapy management
• Drug utilization review
• Step edits
– Patient education to ensure maximizing adherence

21
Patient Management
Plan

Patient Management
Plan

Patient
Education
Materials

22
 Physician Education
Materials

Summary

• Early and effective treatment minimizes the long-term negative

effects of ADHD
– Fewer and less costly emergency department visits
– Fewer traffic accidents
– Better long term employment prospects
• Treatment choices now include
– Longer-acting agents
– New delivery systems
– Availability of non-stimulants
• New delivery system therapies
– Provide continuous treatment of symptoms
– Minimize abuse/diversion potential
– Enhance adherence

Summary (continued)

• Greater adherence to practice guidelines is needed

– Patient and parent education
– Frequent monitoring
– Optimize dosing and medication choice
• Improvement is needed with patient care follow up
– Only 1/3 of all plans achieved the HEDIS performance measure for ADHD
– Implement drug therapy management
– Establish patient registry
– Implement guideline driven care

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