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 Neurochemical

Genetic origins

ADHD
CNS insults Environmental 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

Adults
Wolraich et al. Pediatrics. 2005;115:1734-1746. Millstein et al. J Attention Disorder 1997.

Motoric hyperactivity Low frustration tolerance Impulsiveness Distractibility Shifting of activities Fidgetiness Impatience Restlessness Inattentiveness

3

Evidence of Persistence of ADHD Into Adulthood
80
65 72 66 58

Percentage

60 40 20 0 1 2
4 to 12 12 to 20
31

3
6 to 12 16 to 23

4
6 to 12 21 to 33

5*
6 to 18 16 to 28

Age at diagnosis Age at followup

6 to 17 10 to 21

*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
Cumulative morbidity risk

1 0.8 0.6
ADHD Control

*

*
0.4 0.2 0
MDD BPD OCD Tic disorders ODD

* *

*

CD
*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. 2. 3. 4. 5. 6. 7. 8. 9.

Gittelman R, et al. Arch Gen Psychiatry. 1985;42:937-947. Barkley RA. Attention-Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment, 2nd ed. New York: Guilford Press;1998. Mannuzza S, et al. J Am Acad Child Adolesc Psychiatry. 1997;36:1222-1227. Mannuzza S, et al. Arch Gen Psychiatry. 1993;50:565-576. Weiss G, Hechtman L. Hyperactive Children Grown Up. 2nd ed. New York: Guilford Press 1993. Mannuzza S, et al. Arch Gen Psychiatry. 1989;46:1073-1079. Mannuzza S and Klein RG. Child Adolesc Psychiatr Clin N Am. 2000;9:711-726. Barkley RA. Attention-Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment, 2nd ed. New York: Guilford Press;1998. 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
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.

2

4

6

8

Increased likelihood of outcome compared with age-matched controls

ADHD: Risk of Substance Abuse
Sharp rise in Substance Abuse between mid-adolescence and adulthood
60% 50% 40% 30% 20% 10% 0% Youth Adults 15% 27% 15% 55% Control ADHD

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.

Percent Increase in Risk

5

Sexual Behavior

Casual sex past year Casual sex + infrequent condom use >4 sex partners (lifetime) Pregnancy

P = 0.01 P = 0.02

P <0.001 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

80

P = 0.001

ADHD

Control

Participants (%)

60
P <0.001 P = 0.005

P = 0.019 P <0.001 P = 0.025 P = 0.006

40

20

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

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: Snitroso-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 Methylprenidate (Concerta®) Methylprenidate (Ritalin®) Methylprenidate (Metadate® CD) Methylprenidate (Ritalin® LA) Dexmethylphenidate (Focalin® XR) Methylphenidate (Daytrana®) Amphetamine-based treatments Mixed amphetamine salts (Adderall XR®) Mixed amphetamine salts (Adderall®) Dextroamphetamine (Dexedrine® Spansule) Lisdexamfetamine dimesylate (Vyvanse®) Nonstimulant Atomoxetine (Strattera®)
Physicians’ Desk Reference. 59th ed. Montvale, NJ: Thomson PDR; 2005.

Duration of effect ~12 hours 3–4 hours 8–10 hours ~8 hours 3–4 (8–10) hours ~12 hours (worn for 9) 10–12 hours 4–6 hours 6–8 hours 12 hours Up to 24 hours

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 90 80 70 60 50 40 30 20 10 0 0 10 20
ADHD Control

Risk for SUD (%)

Earlier onset

P ≤0.05, ADHD vs control at endpoint

Higher risk
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
Misused

5% 22% 5% 10% 5% 22% 0% 11%
0% 5% 10% 15% 20% 25%

Got high

No ADHD (n = 43) ADHD (n = 55)

Used too much

Sold

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.
All ADHD
(N = 55)

53% 31% 75% 58% 83% 83% 0% 20% 40% 60% 80%

SUD CD

Misuse
(n = 12)

Divert
(n = 6)

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. 2. 3. 4. 5.

McCabe SE, et al. Addict Behav 2005;30:1342-50. White BP et al. J Am Coll Health 2006;54:261-8. Poulin C. Addiction 2007;102:740-51. Upadhyaya HP, et al. J Child Adolesc Psychopharmacol 2005 ;15 :799-809. 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 IR-MPH OROS-MPH

20

Feel an Effect

15

* *

10

*

5

*

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

Time (hrs) N=6 per group. *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
Bush G, et al. Arch Gen Psychiatry. 2008;65:102-114.

Axial

Coronal

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%
Percent of children <18 years old with diagnosis

Asthma 0.14 0.12 0.08 Respiratory 0.07 Allergy Learning Disability ADHD
A D
(n=61,354) (n=61,354)

15% 10% 5% 0%

lle rg y

a

As th m

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R es pi ra to

(n=73,493)

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

Le ar ni n

(n=73,493)

g

D

is ab ili t

A

HD

y

12

Consequences of Untreated ADHD Increase with Age
• Antisocial Behavior • School Exclusion • Substance Abuse • Conduct Disorder • Lack of Motivation • Complex Learning Disorder

• ADHD only

• Low SelfEsteem

• Disruptive • Oppositional Defiant Behavior Disorder • Poor • Mood Social Disorder Skills • Challenging • Learning Behavior Delay

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

School/Work 46% Expelled4 35% Dropped out4 Lower occupational status5

Family >4x h Sibling fighting9 >4x h Separation/divorce in adulthood10

6. 1. 2. 3. 4. 5. DiScala C, et al. Pediatrics 1998102:1415-21 . Liebson CL, et al. JAMA 2001;285-60-66. Barkley RA, et al. Pediatrics 1996;98:1089-1095. Barkley RA, et al. J Am Acad Child Adolesc Psychiatry 1990;29:546-557. Mannuzza S, et al. J Am Acad Child Adolesc Psychiatry 1997;36:1222-1227. 7. 8. 9. 10.

Biederman J, et al. J Am Acad Child Adolesc Psychiatry 1997;36:21-29. Pomerleau OF, et al. J Subst Abuse 1995;7:373-8. Wilens T, et al. Psychiatr Serv 1995;46:761-3, 765. Mash EJ, Johnston C. J Consult Clin Psychol 1983;51:86-99. Barkley RA, et al. J Child Psychol Psychiatry 1991;32:233-55.

ADHD Associated with Lower Educational Achievement and Income
Fulltime Employed by Academic Achievement Average Income by Academic Achievement

100%

100,000

91.3K

**

75%

72% 56% 55%

77% 65%

80,000
63.0K 66.6K 52.4K

60,000
38.7K 29.5K 23.8K

50%

34%
25%

46.7K

*

22%

30%

40,000

20,000

0% Less than high school High school; some college

0
College; Post-grad some post degree grad

Less than high school

ADHD (n=500) No ADHD (n=501)

High school; some college

College; some post grad

Post-grad degree

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%
Proportion requiring hospital services
p=.005

ADHD No ADHD 75%
n=4119
p=.006

81%

74%

50%

p<.001

41% 33%

26% 25% 18%

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

Out-patient Care

ED Admission

Presence of ADHD Increases Health Care Utilization Costs
Patients 3-17 Years of Age Enrolled in the Group Health Cooperative
$1,500
Costs per patient per year

$1,200 $900 $600 $300 $0

*p <0.001 vs. no ADHD

No ADHD (n=11,968) ADHD (n=2,992)

$1,465*

$690 $427 * $245 $20 Primary Care Mental Health Care $222* $66 Pharmacy Total $335*

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 October 1997

NIH Consensus Statement 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. 2. 3.

American Academy of Pediatrics. Pediatrics. 2001;1081033-44. US Department of Health and Human Services, 1999. 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
Short Acting
SODAS MPH Dexmethylphenidate

Amphetamine
Short Acting Intermediate Long Acting
MAS XR

Intermediate
MPH SR MPH SR

Long Acting

OROS MPH Dextroamphetamine Dextroamphetamine ER Diffucaps MPH Dextroamphetamine tabs MAS MPH LA Dexmethylphenidate XR MPH transdermal patch

Nonstimulant
Approved Atomoxetine Not Approved 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 effect MPH Formulations • Methylprenidate (Concerta®) • Methylprenidate (Metadate® CD) • Methylprenidate (Ritalin® LA) • Dexmethylphenidate [(Focalin® (XR)] • Methylprenidate (Daytrana®) Amphetamine Formulations • Mixed amphetamine salts (Adderall® XR) • Dextroamphetamine (Dexedrine Spansules®) • Mixed amphetamine salts (Adderall®) • Lisdexamfetamine dimesylate (Vyvanse®) Non-Stimulants • Atomoxetine (Strattera®) 12 hours 8-10 hours ~8 hours ~5 (10) hours 7-12+ hours 12 hours ~4 (8) hours 6-8 hours 12 hours 8-24 hours Dosing Schedule

Once daily Once daily Once daily Twice (once) daily Once daily Once daily Multiple Twice daily Once daily Once/twice daily

ADHD Drug Dosing
Medication Methylprenidate (Ritalin) Dexmethylphenidate (Focalin) Methylprenidate (Concerta) Methylprenidate (Metadate CD) Methylprenidate (Ritalin LA) Dexmethylphenidate (Focalin XR) Methylprenidate (Daytrana) Mixed amphetamine salts (Adderall) Mixed amphetamine salts (Adderall XR) Dextroamphetamine (Dexedrine) Dextroamphetamine (Dexedrine Spansules) Lisdexamfetamine dimesylate (Vyvanse) Atomoxetine (Strattera)
Wilens TE, et al. Ann Rev Med. 2002;53:113-131.

Starting Dose 5 mg 2.5 mg 18 mg 20 mg 10 mg 5 mg 10 mg 2.5 to 5 mg 5 to 10 mg 2.5 to 5 mg 5 mg 30 mg 40mg

Maximum Dose 60 mg 10 mg 72 mg 60 mg 60 mg 20 mg 30 mg 40 mg 30 mg 40 mg 50 mg 70mg 100 mg

Dosing Schedule TID BID QD QD QD QD QD BID QD BID/TID BID QD QD/BID

18

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

19

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. 2.

Wolraith EL, et al. Pediatrics. 2005;115:1734-46. 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% 30%
Percent of Plans

33%

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

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Patient Management Plan

Patient Management Plan

Patient Education Materials

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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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