10/13/2023

ADHD Treatment in the Primary Care Setting:

The Teenage Years

Greg Mattingly MD
Associate Clinical Professor, Washington University
President, Midwest Research Group
Co-Chair, US Psych Congress
President Elect, American Professional Society for ADHD and Related Disorders

Disclosures
Dr. Greg Mattingly:
• Consultant- AbbVie, Acadia, Akilli, Alkermes, Angelini, Axsome, Cerevel,
Corium, Eisai, Ironshore, Intracellular, Janssen, Lundbeck, Neos, Neurocrine,
Noven, Otsuka, Redax, Relmada, Revibe, Roche, Sage, Sky Therapeutics,
Sunovion, Supernus, Takeda, Teva, and Tris Pharma.
• Research- AbbVie, Acadia, Alkermes, Akilli, Alto Therapeutics, Avanir,
Axsome, Boehringer Ingelheim, Cingulate, Click Therapeutics, Corium,
Emalex, Intracellular, Janssen, Karuna, Lumos Labs, Neurocrine, Redax,
Relmada, Roche, Sage, Sumitomo. Sunovion, Supernus, Takeda, and Teva;
• Speakers Bureau- AbbVie, Alkermes, Axsome, Corium, Intrcellular,
Ironshore, Janssen, Lundbeck, Neurocrine, Noven, Otsuka, Sunovion,
Supernus, Takeda, and Tris Pharma.

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Learning Objectives
• Understand the course of ADHD from childhood, adolescence and into
young adulthood

• Appreciate the special challenges for teens with ADHD

• Explore treatment strategies for teens with ADHD

ADHD is a Journey

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Developmental Phases:
Changes in Clinical Presentation of ADHD
Related to interplay among environmental demands, external supports available, and
typical symptom trajectories

More

Environmental Demands
Less
Child Teens Young Adult Older Adult
Turgay A, Goodman D et al. J Clin Psychiatry. 2012;73(2):192–201.

Developmental Phases:
Changes in Clinical Presentation of ADHD
Related to interplay among environmental demands, external supports available, and
typical symptom trajectories

More External Supports

Environmental Demands
Less
Child Teens Young Adult Older Adult
Goodman D et al. J Clin Psychiatry. 2012;73(2):192–201.

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Developmental Phases:
Changes in Clinical Presentation of ADHD
Related to interplay among environmental demands, external supports available, and
typical symptom trajectories

More External Supports

Environmental Demands Hyperactivity

Less
Child Teens Young Adult Older Adult

Developmental Phases:
Changes in Clinical Presentation of ADHD
Related to interplay among environmental demands, external supports available, and
typical symptom trajectories

More External Supports

Inattention

Environmental Demands Hyperactivity

Less
Child Teens Young Adult Older Adult

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Developmental Phases:
Changes in Clinical Presentation of ADHD
Related to interplay among environmental demands, external supports available, and
typical symptom trajectories

More External Supports

Inattention

Environmental Demands Hyperactivity

Less
Child Teens Young Adult Older Adult

Developmental Phases:
Changes in Clinical Presentation of ADHD
Related to interplay among environmental demands, external supports available, and
typical symptom trajectories

More External Supports

Inattention

Environmental Demands Hyperactivity

Less
Child Teens Young Adult Older Adult

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DSM 5 Diagnosis of ADHD

• Developmentally inappropriate symptoms
– 6/9 symptoms of inattention, hyperactivity, or combination
– 5/9 if > 17 years of age (older teen or adult)
– 95% of cases are either combined or inattentive subtype
• Age of onset < 12 years
• Not accounted for by other disorder
– Can now make diagnosis of autism spectrum and ADHD
• Diagnosis clinically derived
• Rating scales helpful (parent, school)
– Narrow: Vanderbilt (AAP), others
– Broadband: Child Behavior Checklist
AAP = American Academy of Pediatrics.
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (APA Press); https://doi.org/10.1176/appi.books.9780890425787

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ADHD: Teen Risks and Transitions

Unhealthy Lifestyle
Financial Problems
Occupational Problems
Accidental Injuries and Driving
Risky Sexual Behavior
Smoking and SUDs
Legal Difficulties
Relationships
Academic Failure

Barkley RA, et al. ADHD in Adults: What the Science Says. 2008.

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Developmental Impact of Untreated ADHD

Academic difficulties Occupational failure

Self-esteem issues Self-esteem
Legal issues Relationship
Behavioral Smoking problems
disturbance Injuries Injuries/accidents

Preschool Adolescent Adult

School-age College-age

Behavioral disturbance Academic failure

Academic difficulties Occupational difficulties
Peer relationships Self-esteem
Self-esteem issues Substance misuse
Injuries/accidents

Pliszka S, et al. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921. Brown TE, et al. Postgrad Med. 2010;122(5):42-51. Adler LA, et
al., eds. Attention-Deficit/Hyperactivity Disorder in Adults and Children. Cambridge University Press; 2015.

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Impact of Social Media on ADHD?

3,051 sophomores at 10 high schools in Los Angeles
Estimated mean prevalence of ADHD symptoms across follow-ups, by baseline modern digital media use frequency index derived
from the primary unadjusted repeated measures logistic regression model amongst baseline ADHD symptom–negative students
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18
Mean ADHD Symptom Prevalence

16
Across Follow-Ups, % (+95% Cl)

14% ADHD
14

12

10

0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
n=495 n=337 n=313 n=321 n=268 n=243 n=167 n=114 n=91 n=66 n=54 n=34 n=17 n=16 n=51
Baseline Number of Digital Media Activities Used at a High Frequency Rate

Ra CK, et al. JAMA. 2018;320(3):255-263.

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Young Adults with ADHD Manifest More

Social Difficulties
Income <25K
HS dropout
ADHD Control
College graduate
Recreational drug use
Addicted to tobacco or smoking
Employment
Been arrested
Been divorced

Sexual problems

0 10 20 30 40 50 60 70 80
Percentage

Survey of 500 community adults with ADHD compared with 501 age- and
gender-matched controls; 36% of the ADHD group reported current medication use

Biederman J, et al. J Clin Psychiatry. 2006;67(4):524-540.

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ADHD and Sexual Behavior

• Milwaukee follow-up study of boys with ADHD vs

controls:
– Sexual intercourse at earlier age (15 yrs vs 16 yrs)
– More sexual partners (19 vs 7)
– More teen pregnancies (38% vs 4%)
– More sexually transmitted diseases (17% vs 4%)

Barkley RA, Gordon M. Research on comorbidity, adaptive functioning, and cognitive impairments in
adults with ADHD: implications for a clinical practice. In: Goldstein S, Ellison AT, eds. Clinician’s Guide
to Adult ADHD: Assessment and Intervention. San Diego, CA: Academic Press; 2002:43-70.

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Differential Brain Development May

Explain Observable Problems in ADHD
Adolescents and Young Adults

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Significant brain growth and development occurs during

adolescence, and continues into the twenties. Some studies show that
this growth and development extends to the age of 30!

(Sowell et al., 1999; Sowell et al., 2001)

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Limbic System: Develops Early

• “Emotional circuitry”
Emotion
Arousal
Reward
Risky Behavior

• Maturation influenced by
hormones
Different for boys & girls

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The Frontal Lobes: Develop Later

“Executive Functions”
 Governing emotions
 Judgment
 Planning
 Organization
 Problem Solving
 Impulse Inhibition
 Abstraction
 Analysis/synthesis

*Self- “everything”

Williamsgroup, 2003: Please credit Protecting You/Protecting Me (PY/PM)

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Delayed Prefrontal Brain Maturation in ADHD

Greater than 2 years’ delay

Ns: ADHD = 223; Controls = 223 0 to 2 years delay

Shaw P et al. Proc Natl Acad Sci USA. 2007;104:19649-19654. Reprinted with permission from the National
Academy of Sciences USA. © 2007.

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Transitional Aged Youth Behavior ?

Dysregulated
Mood
(e.g. frustration,
Irritability, temper tantrums)

Exaggerated in SUD, ADHD, or

Mood dysregulation ?
Casey et al., 2008
Courtesy N Strang
Courtesy of Tim Wilens MD, MGH

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Social Issues in Young People with ADHD

Less socially competent than peers1

Involved in fewer social activities2
Fewer friends2
Delinquent friends3
Social isolation3
Adolescents with ADHD report an
overly optimistic appraisal of their social
adjustment

Adler, Spencer, Wilens (eds): ADHD in Children and Adults, Cambridge

Press 2015; Riglin et al., J Clin Psych: 2023:84(2):22m14379
1998.

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Overlapping Symptoms of ADHD and Comorbidities

ADHD Symptoms ADHD-

related
Hyperactivity Impulsivity Inattention symptoms

Mood disorders Mood swings

Excessive Restlessness/ Racing Impulsive Difficulty Decreased
/anger
talking agitation thoughts behaviours concentrating attention
outbursts

MDD
Conduct
disorders
Bipolar disorder
(hypomania)
Anxiety
SUD
Sleep disorders

Adapted from Kooij S, et al. J Atten Disord. 2012;16:3S-19S. Kim EY, Miklowitz DJ. Bipolar Disord. 2002;4:215-225.

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Educational Level of Adults with ADHD

60 Untreated ADHD ‘Costs’ 10 IQ Points

50
Observed Expected
40
Subjects

z=-7.98, p<0.001
% of

30
20
10
0
Less than Junior Partial High Partial College Graduate
7th grade High High School College Graduate Degree
School School Graduate

Biederman et al, J Clin Psychiatry 2008;69:1217–1222

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Comorbidities in College-Age Adults

Important Considerations in Our Differential
N=443 (214 men and 229 women), ages 18 to 22 years (M = 18.2 years),
recruited from 9 colleges involved in a large-scale, multisite longitudinal investigation

Comorbid and Non-ADHD Disorders by Group

Disorder % ADHD % Comparison P OR
Depressive 32.3 5.4 <.001 8.4
Anxiety 28.6 3.6 <.001 10.8
GAD 15.5 1.8 <.001 10.0
Trauma and Stressor 7.3 0.9 .001 8.7
Learning Disorder 10.0 0.4 <.001 24.7

College students with ADHD: 55% had at least 1 comorbid condition and 31.8% had ≥ 2
College students without ADHD: 11.2% and 4.0%, respectively

Anastopoulos AD, et al. J Clin Child Adolesc Psychol. 2018;47(2):236-247.

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Why Do We See an Increased Prevalence of

Athletes with ADHD?

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Trends in Stimulant Prescription Fills (2016-2021)

Largest Growth in 15-24 yo Women
Relative annual percent change in percentage of persons aged 5–64 years

• At least one
stimulant
prescription fill
• Data by sex and
age group

Danielson ML, et al. Trends in Stimulant Prescription Fills Among Commercially Insured Children and Adults — United States, 2016–2021.
CDC. March 31, 2023. Accessed May 3, 2023. https://www.cdc.gov/mmwr/volumes/72/wr/mm7213a1.htm.

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Wall Street Journal

July 6th 2023

Reddy S. You May Have Adult ADHD, but Not Because TIkTok Says So. Wall Street Journal. Updated July 6, 2023. Accessed August 2023.
https://www.wsj.com/articles/adult-adhd-symptoms-treatment-diagnosis-4c371108.

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www.samhsa. gov/data/sites/default/files/NSDUH-DetTabs2013.pdf

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ADHD Increases the Risk for Substance Use

Disorders (SUD) in Young adults with
ADHD

ADHD (N=361)

Controls (N=417)

(Wilens et al. J Am Acad Child Adoles Psychiatry: 2011)

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Misuse of Prescription Psychotherapeutics

Mean Age at First

Misuse of Prescription
Psychotherapeutics
among People Aged
12 to 49 Who Initiated
Misuse in the Past
Year, by Drug Type:
2015

Hughes A, et al. Prescription Drug Use and Misuse in the United States: Results from the 2015 National Survey on Drug Use and Health.
SAMHSA: NSDUH Data Review. September 2016. Accessed May 9, 2023. https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR2-
2015/NSDUH-FFR2-2015.htm.

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Stimulant Misuse and Diversion

• N>120 studies
• 10% to 20% prevalence of non-medical use of stimulants
• 65% to 85% of stimulants diverted from “friends”
– Majority not “scamming” local docs
– Not seen as potentially dangerous
• Motivation typically for concentration and alertness more so than
getting “high”
• High rates of ADHD and neuropsychological deficits
• Appears to be occurring in substance (ab)users during academic
decline
• Immediate-release > > extended-release stimulants
• High rates of intranasal misuse of stimulants

Wilens TE, et al. J Am Acad Child Adolesc Psychiatry. 2008;47(1):21-31.. Wilens TE, et al. J Clin Psychiatry. 2016;77(10):1420-1427. Wilens
T et al., Am J Addiction 2017: 26(4):379-387. . Monitoring the Future (www.monitoringthefuture.org). www.monitoringthefuture.org.
Faraone SV, et al. J Am Acad Child Adolesc Psychiatry. 2019;59(1):100-112.

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Longer Term Treatment of Childhood

Psychopathology Reduces the Risk for
Subsequent
RESULTS SUD

• PRISMA based search of the literature

examining the long-term impact of treating
psychopathology with pharmacotherapy in
childhood
• N= 21 studies in ADHD, 2 studies on Major
Depression, and 3 studies on psychotic disorders
• Majority reported reductions in SUD (N=14) followed
by no effects (N=10) and enhanced rates of SUD
(N=2)
• Earlier-onset and longer-duration treatment was
associated with the largest SUD risk reduction

(Wilens et al., J Child Adolesc Psychopharm. November, 2022)

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MGH Study: Treatment of ADHD Improves

Retention in SUD Treatment
N=171 treated ADHD
N=32 untreated ADHD
Early Tx >> later Tx [90d]

Treated ADHD

Untreated ADHD

Kast KA, et al. J Clin Psychiatry. 2021;82(2):20m13598.

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Real-World Stimulant Prescription Data

Adult Pediatric

Short-acting
21%
Short-acting
Long-acting
48%
52%
Long-acting
79%

Overall Rx volume: 23.51M

Overall Rx volume: 55.40M

Rx = prescription.
Source: IQVIA XPO data 11/1/2021-10/31/2022. Pediatric ages 0-18 years, Adult age 18+ years. Includes stimulants only
(amphetamine/methylphenidate) 3
6
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Transition from Methylphenidate to Amphetamine

Occurs in Adolescence
% of US Stimulant Perscriptions1,2

80%

70% 76%
69% Amphetamine
60% 54%

50% 47%

40% 45%
38%
30% 26%
20%
20%
Methylphenidate
10%

0%
0-12 13-17 18-24 >25

1. Data Source: IMS NPA Market Dynamics - RETAIL Rx ONLY.; 2. Mattingly GW, et al. CNS Spectr. 2016;21(S1):45–59.

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Currently Approved ADHD Medications Reflect

Limited Distinct Approaches for Adult Patients
Stimulants1,2 Non-Stimulants1

Short-Acting Atomoxetine4
Approved2 Viloxazine XR
Amphetamine6 (kids and adults)

Long-Acting ER α2 adrenergic agonists5

(kids and adults)
Investigational Several MOAs
under investigation
Short-Acting

Methylphenidate3
Long-Acting
(kids and adults)

1. Cohen Children's Medical Center. The ADHD Medication Guide. Updated January 1, 2022. Accessed May 4, 2022.
http://www.adhdmedicationguide.com/pdf/adhd_med_guide_123021.pdf; 2. US Food and Drug Administration: FDA Approved Drug
Products. Accessed May 4, 2022. www.accessdata.fda.gov/scripts/cder/daf/; 3. De Sousa A, et al. Mens Sana Monogr. 2012;10:45-69;
4. Spencer TJ, et al. J Clin Psychiatry. 2002;63 (Suppl 12):16-22; 5.Stahl SM, et al. Prim Care Companion J Clin Psychiatry. 2004;6:159-
166; 6.Chang SC, et al. J Exp Clin Med. 2013;5:210-216.

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Transitioning from IR to ER/XR

IR = immediate release; SR = sustained release; ER/XR = extended release; LA = long acting; CD = controlled delivery; PM = evening;
ODT = orally disintegrating tablets.
Aiken C. How to Switch Stimulants: A Dosing Guide for ADHD. Psychiatric Times. May 9, 2021. Accessed August 2023.
https://www.psychiatrictimes.com/view/how-to-switch-stimulants-dosing-guide-for-adhd?slide=5.

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Agents with Varied Durations

Dose will need more adjusting due to:

Switch from Methylphenidate to

Amphetamine
Different isomer ratios
Compounds with unique delivery systems

Aiken C. How to Switch Stimulants: A Dosing Guide for ADHD. Psychiatric Times. May 9, 2021. Accessed August 2023.
https://www.psychiatrictimes.com/view/how-to-switch-stimulants-dosing-guide-for-adhd?slide=6.

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Dosing Adjustments from Methylphenidate to

Amphetamine
Adderall is “twice as potent” as
Methylphenidate

Not one stop shopping – many alternatives

Brand names may be covered by insurance vs
generic
Off label use
Co-pay cards, different pharmacies, discount cards,
prior authorizations
Krevskaya A, et al. What to Do When You Can’t Get the ADHD Medication You Want. CHADD. June 2018. Accessed August 2023.
https://chadd.org/wp-content/uploads/2018/10/Cant_Get_ADHD_Meds.pdf.

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Nonstimulant Options
Delivery Mechanism and Approved Dosing Onset Duration of
Generic Name Comments
Formulation Ages per Day Effect Effect
Long-Acting
 Norepinephrine
Children ≥ 6,
transporter reuptake Atomoxetine* adults
1 to 2 3 to 4 wk NA  Dosed by body weight
inhibitor capsule
*  An antihypertensive
agent may be
 Alpha2-adrenergic prescribed in addition to
Clonidine HCL Children ≥ 6 2 2 wk NA
receptor agonist tablet a stimulant
 Discontinuation must
be gradual
 An antihypertensive
agent may be
 Alpha2-adrenergic Up to 24 hr
Guanfacine Children ≥ 6 1 3 wk prescribed in addition to
receptor agonist tablet per dose
a stimulant
 Dosed by body weight
 Serotonin
ViloxazineXR Children ≥ 6,
norepinephrine
adults 1 1 wk 24 hr
modulating agent HCL*
capsule

*Only nonstimulants approved in adults.

Mattingly GW, et al. CNS Spectr. 2021;26(3):202-221.

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Adding a Stimulant to a Nonstimulant?

OROS MPH Added to Atomoxetine

Wilens T et al. JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 19, Number 5, 2009 Pp.485–492.

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Do Any Nonstimulants Work After You Have Tried

A Stimulant?

Viloxazine for
Adults Who Have
Already Tried a
Stimulant

Mattingly GW, et al. Presented at: 2023 ASCP Annual Meeting; June 1, 2023; Miami, Florida. Poster.

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Improving Communication in ADHD Care:

Results from In-office Linguistic Research

KEY TAKE HOME: Kids are the patient!

Mattingly G, et al. CNS Spectrums. 2011;16(4):85-94.

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Impact of ADHD on the Family

Assessed prevalence, frequency and impact of functional impairments on the
caregiver, spouse/partner, and siblings of children and adolescents with ADHD

p < 0.001 ADHD

vs non-ADHD

Faraone SV et al. J Child Adolesc Psychopharmacol 2017;27:715–22

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MGH Randomized Controlled Trial of CBT for

ADHD in Medication Treated Adolescents
4-month responder status (% responders, n=46)
Parent report Adolescent report
70 70

60 60

50 50

40 40

30 30

20 20

10 10

0 0
CBT Wait list CBT Wait list
30% reduction on the ADHD rating scale = categorical responder, (chi sq [1] = 8.98, P=.00 for parent; chi sq [1] = 5.87, P=.02 for adolescent)
Sprich SE, et al. J Child Psychol Psychiatry. 2016;57(11):1218-1226.

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Engaging Teens

Adolescent ADHD
“Values”
• Helps families find their why

• Helps parents resolve dilemmas

when they know their teen’s
values

• Link values to desire to

participate in therapy

Courtesy of Sibley M- STAND Program

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Developing a Treatment Plan:

Education and Support
 Educate about ADHD and the individual’s strengths
and weaknesses
 Use local and online resources for education and
support
 Aid in implementation of home, work, school, lifestyle
accommodations (eg, quiet work space, extra time for
tests)
 Consider vocational assessment/career counseling
 Set reasonable expectations of pharmacologic and
psychosocial treatment

Pliszka; AACAP Work Group on Quality Issues. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921. Available at:
http://www.aacap.org/cs/root/member_information/practice_information/practice_parameters/practice_parameters.
Accessed January 19, 2009. Murphy. J Clin Psychology. 2005;61:607-619.

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ADHD Strategies for College

• Understand ADHD and accept the need to seek out help
• Seek accommodations such as extended time for tests, a
scribe for note taking, writing/math tutoring centers
• Develop positive self-care habits (adequate sleep and
nutrition, exercise, stress-management techniques)
• Create structure (regular study periods)
• Take a reduced load, especially during the first semester
• Take medication regularly (not just as needed/ PRN)
• Learn to study during medication-coverage times

National Resource Center on ADHD. What We Know. 13: Succeeding in College. 2002.
www.help4adhd.org.

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“Study Like an Athlete”

7 tips for success
1. Prepare for the start of each school year
2. Get your sleep cycle back on track
3. Come prepared
4. Look forward to 1 thing each day
5. Play to win!
6. Be part of the team
7. Compliment those around you

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How Many Patients With ADHD Do You Have To Treat To

Prevent...
NNT With ADHD Treatment:
• 3
– Developing conduct disorder
– Developing an anxiety disorder
– Developing oppositional disorder
– Repeating a Grade
• 4
– Developing major depression
– Having a car accident
• 5
– Developing bipolar disorder
• 6
– Smoking cigarettes
• 10
– Developing substance use disorder

Biederman et al. J Adolesc Health. 2019 Jul 3. pii: S1054-139X(19)30305-2. doi: 10.1016/j.jadohealth.2019.05.015

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ADHD Is Too Important To Ignore

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