therapeutic advances and follow-up strategies …...therapeutic advances and follow-up strategies...

Therapeutic Advances and Follow-Up Strategies across the Lifespan for Patients with ADHD

Anthony L. Rostain, MD, MA

Professor of Psychiatry and PediatricsUniversity of Pennsylvania Perelman School of MedicineMedical Director, Adult ADHD Treatment & Research Program, Penn Behavioral HealthDevelopmental Neuropsychiatry Program, The Children’s Hospital of PhiladelphiaPhiladelphia, Pennsylvania

Supported by an educational grant from Shire, now part of Takeda.

Faculty Disclosure

• Dr. Rostain: Royalties—Routledge/Taylor Francis Group, St. Martin’s Press; Scientific Advisory Board—Shire/Takeda, Arbor Pharmaceuticals.

Disclosure

• The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational use(s) of drugs, products, and/or devices (any use not approved by the US Food and Drug Administration).– Dr. Rostain will be discussing off-label use of medications in this presentation

and will identify those medications.

• Applicable CME staff have no relationships to disclose relating to the subject matter of this activity.

• This activity has been independently reviewed for balance.

• Brand names are included in this presentation for participant clarification purposes only. No product promotion should be inferred.

Learning Objectives

• Describe barriers across the patient lifespan that can interfere with medication adherence in patients with attention-deficit/hyperactivity disorder (ADHD)

• Discuss available stimulant formulations for the treatment of ADHD and their indications and risk/benefit profiles across patient age groups

• Incorporate best practices for patient follow-up into ADHD management plans to achieve long-term treatment adherence and success

Brief Overview of ADHD

What the Science Says

Summary of ADHD Science

• ADHD is a complex, heterogeneous, genetically determined neurodevelopmental lifespan disorder affecting patient, family, and community

• ADHD has different trajectories of development and multiple determinants of clinical course

• There is a high degree of overlap with other neurodevelopmental disorders and comorbid psychiatric conditions

• Recent definitions of ADHD underscore impairments in executive functioning that have significant cognitive, emotional, and behavioral consequences that lead to multiple impairments

Barkley RA (Ed). Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. New York, NY: Guilford Press; 2015. Faraone SV, et al. Nat Rev Dis Primers. 2015;1:15020. Asherson P, et al. Lancet Psychiatry. 2016;3(6):568-578.

Summary of ADHD Science (cont’d)

• No single neuropsychological theory or neurobiological model can explain the heterogeneity seen in ADHD

• ADHD occurs universally, across societies, cultures, classes, ethnicities

– In the United States: 7% to 9% of children, 3% to 5% of adults

– Sex ratios: boys vs girls = 2:1; men vs women = 3:2

• ADHD largely results from biological factors

– Genetics, neurology, acquired injuries, and interactions

– 25% to 35% from injuries; 65% to 75% from genetics

• Social factors likely influence degree of impairment, risk for comorbid disorders, and access to resources

Barkley RA (Ed). Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. New York, NY: Guilford Press; 2015. Faraone SV, et al. Nat Rev Dis Primers. 2015;1:15020. Asherson P, et al. Lancet Psychiatry. 2016;3(6):568-578.

Faraone SV, et al. Nat Rev Dis Primers. 2015;1:15020.

Clinical Progression PathophysiologyEtiology

Frontal–subcortical–cerebellar dysfunction via structural and functional brain abnormalities and

downregulation of catecholamine systems that regulate attention, reward, executive control, and

motor functions

Different genetic risk factors affect the course of ADHD at different stages of the lifespan

Psychosocial influences, chaotic family environments, peer influences, and mismatch with school

and/or work environments

Inattention persists and hyperactive–

impulsive symptoms wane

Substance abuse, low self-esteem, and

social disability

Behavioral disinhibition, emotional ability, and

emergence of diagnosis in preschool yearsFull expression of ADHD,

psychiatric comorbidity,

school failure, peer rejection,

and neurocognitive

dysfunction

Sm

ok

ing

Init

iati

on

Genetic

predisposition

Fetal exposures

and

epigenetic changes

Prodrome: hyperactivity; and speech,

language, and motor coordination problems

In utero Adolescence AdulthoodChildhood

Persistence of cortical thickness, default-

mode network, and white matter tract

abnormalities

Summary: Neurobiology of ADHD

PFC = prefrontal cortex.

Tripp G, et al. Neuropharmacology. 2009;57(7-8):579-589.

Noradrenaline Dopamine Serotonin

Genes

PFC Basal ganglia Cerebellum

Neural

Mechanisms

DBH HTR1B DAT1 D4 D5 SER T SNAP-25

Basic

Processes

ADHD

Executive Function

Working

memory

Behavioral

inhibition

Motivation

Delay

aversionReinforcement

Predominantly

inattentivePredominantly

hyperactive–impulsiveCombined

Symptoms

Regulation of Attention and Emotion

Arnsten AF, et al. J Am Acad Child Adolesc Psychiatry. 2012;51(4):356-367.

Hypothalamus

Basal Ganglia

Sensory

Cortices Premotor

Cortices Inhibit

Inappropriate

Actions

Top-Down

Guidance

of Attention

and Thought

Regulate

Emotion

Cerebellum

Arousal/Reward

Systems

Dorsal

Ventral

Prefrontal Cortex

Amygdala

The Prefrontal Cortex Requires a Proper Level of Catecholamines for Optimal Function

Arnsten AF. J Pediatr. 2009;154(5):I-S43.

Increasing Levels of Catecholamine Release

Drowsy Alert Stressed

Unguided attention / responses

Distracted, poor impulse control

(eg, Untreated ADHD)

Misguided attention / responses

Mental inflexibility, stimulus bound

(eg, Excessive dose of stimulant)

Guided attention and responses

Focused, organized, and flexible

(eg, Optimally treated ADHD)

NE a2A

Moderate D1

Too little

a2A/D1

NE a1, b1

Excess D1

ADHD Treatment across the Lifespan

Treatment Modalities for ADHD

• PSYCHOEDUCATION is critically important

• ALL treatments work to some extent

• Combined treatment is preferred

Dulcan M. J Am Acad Child Adolesc Psychiatry. 1997;36(10 Suppl):85S-121S. Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management, et al. Pediatrics. 2011;128(5):1007-1022.

• ADHD is a complex, heterogeneous, genetically determined neurodevelopmental lifespan disorder that is optimally treated with combined medical and psychosocial approaches

Medical

Interventions

Educational / Workplace

Interventions

Psychosocial

Interventions

Evidence-Based Behavioral Treatments for ADHD

Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management, et al. Pediatrics. 2011;128(5):1007-1022.

Intervention Type Description Typical Outcome(s) Median Effect Size

Behavioral Parent Training

(BPT)

Behavior-modification principles

provided to parents for

implementation in home settings

Improved compliance with

parental commands; improved

parental understanding of

behavioral principles; high levels

of parental satisfaction with

treatment

0.55

Behavioral Classroom

Management

Behavior-modification principles

provided to teachers for

implementation in classroom

settings

Improved attention to

instruction; improved

compliance with classroom

rules; decreased disruptive

behavior; improved work

productivity

0.61

Network Meta-Analysis: Results of ADHD Treatment

Cortese S, et al. Lancet Psychiatry. 2018;5(9):727-738.

Mean Change in ADHD Symptoms – Rated by Clinicians

Children and Adolescents Adults

SMD (95% CI) SMD (95% CI)

Amphetamines -1.02 (-1.19 to -0.85) -0.79 (-0.99 to -0.58)

Atomoxetine -0.56 (-0.66 to -0.45) -0.45 (-0.58 to -0.32)

Bupropion -0.96 (-1.69 to -0.22) -0.46 (-0.85 to -0.07)

Clonidine -0.71 (-1.17 to -0.24)

Guanfacine -0.67 (-0.85 to -0.50)

Methylphenidate -0.78 (-0.93 to -0.62) -0.49 (-0.64 to -0.35)

Modafinil -0.62 (-0.84 to -0.41) 0.16 (-0.28 to 0.59)

0.5-1 -0.5 0

Favors PlaceboFavors Drug

0.5-1 -0.5 0

Favors PlaceboFavors Drug

Outline of Interventions and Referral of Individuals with ADHD in Primary Care

Based on NICE Guideline CG72. National Institute for Health and Care Excellence (NICE). Attention deficit hyperactivity disorder: diagnosis and management. March 2018. www.nice.org.uk/guidance/ng87. Accessed March 14, 2019.

Refer parents / carers

for parent-training /

education

Refer to tertiary service

if problems persist

Moderate / severe

impairment and no childhood

diagnosis for ADHD

Childhood ADHD

with continuing significant

impairment

Refer for ADHD

specialist assessment

Refer for general adult

psychiatrist assessment

Drug treatment

not recommended

Post-diagnosis of ADHD

• Drug treatment first line

• Psychological treatment, eg, CBT (if drug treatment is

refused)

• Offer advice regarding:

• Self-help groups

• Support groups

• Voluntary organizations

• Diet

• General care

PRESCHOOL CHILDREN CHILDREN and YOUNG PEOPLE ADULTS

Mild / moderate

impairment

Severe

impairment

On medication for

ADHD without formal

ADHD diagnosis

Watchful waiting

up to 10 weeks

Refer to secondary care

for assessment

Refer to ADHD specialist

as a clinical priority

Refer parents / carers

for parent-training /

education (need not

wait for formal diagnosis)


• Drug treatment most effective

• Psychological treatment (if drug treatment is refused)

• Parent-training / education

• Classroom behavioral interventions

Refer to secondary care

for assessment if

problems persist with

moderate impairment


• Parent-training / education

• Psychological treatment

• Classroom behavioral interventions

• Drug treatment if significant impairment

Offer advice regarding:

• Self-help groups

• Support groups

• Voluntary organizations

• Diet

• General care

• Behavior management —

– Parent-training / education

– Psychological treatments

FAMILIES and CARERS

Pharmacologic Treatment of Childhood ADHD with No Significant Comorbid Disorders

Goodman DW. Primary Psychiatry. 2010;17(2):46-63.

Diagnostic Assessment and Family Consultation

Regarding Treatment Alternatives

MPH or AMPH

Stimulant not used in Stage 1

Atomoxetine

Bupropion or TCA

Agent not used in Stage 4

Alpha Agonist

Clinical Consultation

Nonmedical Treatment Alternatives

Continuation

Continuation

Continuation

Continuation

Continuation

Maintenance

Stage 1A (optional)

AMPH formulation not used in Stage 1

Stage 2A (optional)

AMPH formulation not used in Stage 2

Stage 3A (optional)

Combine stimulant and atomoxetine

STAGE 0

STAGE 1

STAGE 2

STAGE 3

STAGE 4

STAGE 5

STAGE 6

Response

Response

Response

Response

Response

Partial Response or Nonresponse



Partial Response

(if MPH or AMPH used in Stage 1)

Partial Response

(if MPH or AMPH used in Stage 2)

Partial Response

to stimulant or atomoxetine

Response

Response

Response






Stimulant not used in Stage 1

Atomoxetine

Any stage(s) can be skipped

depending on the clinical picture

Treatment Guidelines for Adults with ADHD

• A typical sequence of interventions:

– Education

– Medication Trial Efficacy/SafetyCanadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA). Canadian ADHD Practice Guidelines, Third Edition. Toronto, ON: CADDRA; 2011. www.caddra.ca/pdfs/caddraGuidelines2011.pdf. Accessed March 14, 2019.

• Drug treatment is first-line treatment for adults with ADHD with either moderate or severe levels of impairment

National Institute for Health and Care Excellence (NICE). Attention deficit hyperactivity disorder: diagnosis and management.March 2018. www.nice.org.uk/guidance/ng87. Accessed March 14, 2019.

• Drug prescribing in adults is supported by British Association Psychopharmacology guidelines

Bolea-Alamañac B, et al. J Psychopharmacol. 2014;28(3):179-203.

SES = socioeconomic status.

Corkum P, et al. Atten Defic Hyperact Disord. 2015;7(1):49-74.

Treatment

Barriers

Personal

Characteristics(sex, age,

ethnicity, SES,

comorbidity)

Structural

Barriers(financial burden,

system

barriers)

Perceptions

of ADHD(knowledge of

ADHD, severity,

and cause,

normality)

Perceptions

of Treatment(treatment

acceptability,

stigma)

Barriers to Medication Adherence

• Suboptimal/inadequate response

• Adverse effects: physical/psychological

• Inconvenience / effortful demands of taking medication regularly / multiple dosing

• Financial expense / insurance policy limits

• Availability of medications / supply issues

• Forgetfulness / disorganization / executive functioning skills deficits

• Oppositional behavior/ defiance / testing limits / autonomy

• Negative attitudes about medications

• Demoralization, defeatism, hopelessness

• Social stigma / self-stigma

Rostain AL. Improving Treatment Adherence of Patients with ADHD. Presented at: CADDRA 13th Annual Meeting; October 29, 2017; Quebec City, Canada.

Barriers to Psychosocial Treatment Adherence

• Time commitment of therapy (including travel time)

• Lack of shared involvement by key family members

• Effort and energy required to make behavior changes

– “Homework assignments” / modification of routines, habits / tracking behavior

• Financial expenses / insurance barriers

• Availability of competent clinicians

• Social stigma / self-stigma

• Internalized doubts about the effectiveness of treatment

– Demoralization, defeatism, hopelessness


Strategies for Improving Treatment Adherence➢ Enhancing clinician-patient communication / alliance-building

➢ Creating a collaborative framework for working together on “issues”

➢ Remaining nonjudgmental, compassionate, and hopeful about change

➢ Defining realistic goals, expectations, and time frame for treatment➢ Picking best treatment options to meet patient’s/family’s priorities

➢ Addressing sources of treatment resistance (eg, adverse effects)➢ Staying continually aware of new or persistent barriers to adherence

➢ Sustaining focus on patterns of avoidance underlying nonadherence (including misuse)

➢ Placing emphasis on managing transitions, especially youth and young adults

➢ Re-evaluating treatment practices to foster realistic outcomes


• Adherence to treatment can be improved by establishing a close collaborative relationship, monitoring treatment efficacy, looking for problems with tolerability, and educating about risks of misuse

Evaluating Current Stimulant Formulations

Neurotransmitters and ADHD Medications

NH2

HO

OH

dopamine

NH2

HO

OH

OH

norepinephrine

N*

HH3COOC

* methylphenidate

CH3

HN*

H

amphetamine

H3C

O

NH

atomoxetine

CH3

Summary of Stimulant Action

• Methylphenidate

– Blocks reuptake of transmitter into presynaptic terminal

• Amphetamine– Releases transmitter from vesicle– Blocks reuptake of transmitter

into vesicle– Blocks reuptake of transmitter

into presynaptic terminal– Induces release of transmitter

when it is absorbed into the presynaptic terminal

– D-form acts on DA neurons; L-form acts on NE neurons

Hodgkins P, et al. Eur Child Adolesc Psychiatry. 2012;21(9):477-492. Heal DJ, et al. Neuropharmacology. 2009;57(7-8):608-618. Easton N, et al. Neuropharmacology. 2007;52(2):405-414.

Vesicle

Cytosolic

dopamine

AMPH targets

VMAT2 causing

release of dopamine

into the cytoplasm

AMPH reverse

dopamine uptake

via the dopamine

transporter

AMPH inhibits

dopamine

transporter

Synapse

Presynaptic

dopamine neuron(b)

Vesicle

Dopamine

transporterMPH inhibits

dopamine

transporter

Synapse

Presynaptic

dopamine neuron(a)

Cytosolic

dopamine

Psychostimulants: Overview

• Beneficial effects seen in > 80% of patients

– Decreased activity level

– Improved motor performance

– Increased cognitive performance

– Decreased conduct problems

– ? School achievement

– ? Interpersonal relationships

• Psychostimulants first-line agents

– Multiple FDA approved agents • Long-acting preparations preferable

– Better adherence, treat through the day

– Minimize potential for misuse or abuse

• May be useful to orient according to weight– eg, 1–1.5 mg/kg/day MPH ~ 70–100 mg/day

– 0.5–1.0 mg/kg/day MAS

Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA). Canadian ADHD Practice Guidelines, Third Edition. Toronto, ON: CADDRA; 2011. www.caddra.ca/pdfs/caddraGuidelines2011.pdf. Accessed March 14, 2019.

Psychostimulants: Overview (cont’d)

• Adverse effects are generally well tolerated– Reduced appetite and consequent weight loss

– Abdominal pain, nausea, constipation

– Difficulty falling asleep

– Mild increase in heart rate and blood pressure

– Jitteriness, jumpiness

– Motor tics

– Dysphoria, moodiness, irritability

– Rebound effects

Pliszka SR. J Am Acad Child Adolesc Psychiatry. 2006;46(7):894-921. Daughton J, et al. In: Martin A, et al (Eds). Pediatric Psychopharmacology: Principles and Practice. Second Edition. New York, NY: Oxford Press; 2011.

• Stimulants are the most effective medications for ADHD across the lifespan; they can be prescribed safely and appropriately by using established treatment guidelines

Pharmacologic Treatments

Approved for ADHD

Wilens TE, et al. Postgrad Med. 2010;122(5):97-109. Stevens JR, et al. In: Adler LA, et al (Eds). Attention-Deficit Disorder in Adults and Children. Cambridge University Press: Cambridge, UK; 2015:245-258.

Amphetamine-based Formulations Duration of Effect Adult Approved?

Adderall® (MAS) 4–6 hours

Adderall XR® (MAS XR) ~12 hours YES

Dexedrine® Spansule (dextroamphetamine) 6–8 hours

Vyvanse® (lisdexamfetamine) ~12 hours YES

Methylphenidate-based Formulations

Concerta® (MPH) ~12 hours YES

Daytrana® (MPH patch) ~12 hours (worn for 9)

Focalin® (dexMPH capsule) ~5 hours

Focalin® XR (dexMPH XR capsule) 10–12 hours YES

Metadate® CD (MPH controlled-release capsule) 8–10 hours

Ritalin® (MPH) ~4 hours

Ritalin® LA (MPH XR capsule) 8–10 hours

Quillivant XR® (MPH XR liquid) ~12 hours

Nonstimulants

Strattera® (atomoxetine) 8–24 hours YES

Intuniv® (guanfacine XR) ~12 hours

Kapvay® (clonidine XR) ~12 hours

Pharmacologic Treatments Approved for ADHDNewer Methylphenidate Preparations

CR = controlled-release; ER = extended-release; IR = immediate-release; ODT = orally disintegrating tablet.

US Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. www.accessdata.fda.gov/scripts/cder/daf/.

Delivery Brand Name Formulation Age Approved Dose Range

Liquid Methylin® IR solution 6–17, adults 5–60 mg

Quillivant XR® 20% IR, 80% ER 6–17, adults 20–60 mg

ODT Cotempla XR-ODT® 25% IR, 75% ER 6–17 17.3–51.8 mg

Chewable Tablet Methylin® IR 6–17, adults 5–60 mg

Quillichew ER™ 30% IR, 70% ER 6–17, adults 20–60 mg

Capsule Aptensio XR™ 40% IR, 60% CR 6–17, adults 10–60 mg

Transdermal Patch Daytrana® ER 6–17 10–30 mg

Pharmacologic Treatments Approved for ADHD Newer Amphetamine Preparations

DR = delayed-release.

US Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. www.accessdata.fda.gov/scripts/cder/daf/.

https://independencepharma.com/wp-content/uploads/2018/10/ProCentra-PI-and-MedGuide.pdf. https://zenzedi.com/.

Delivery Brand Name Formulation Age Approved Dose Range

Liquid Dyanavel™ XR ER suspension 6–17 2.5–20 mg

ProCentra® IR solution 3–16 2.5–40 mg

ODT Adzenys XR-ODT™ 50% IR, 50% DR 6–17, adults 6.3–18.8 mg

Chewable Tablet Vyvanse® Continuous ER 6–17, adults 30–60 mg

Capsule Mydayis® Triple bead ER 13–17 adults 12.5–50 mg

Tablet Evekeo® IR (D-, L- 50%) 3–17 2.5–40 mg

Zenzedi® IR 3–17 2.5–40 mg

16%Responded

better to MPH

than AMPH

28%Responded

better to AMPH

than MPH

Methylphenidate vs Amphetamine

Mattingly GW, et al. Postgrad Med. 2017;129(7):657-666. Arnold LE. J Atten Disord. 2000;3(4):200-211.

41%

Responded to

both AMPH

and MPH

(“double

responders”)

13%

Did not respond to either medication

Most patients (n=152/174; 87%) responded to either

MPH and/or AMPH

In Pediatric Studies

Why Adult ADHD Needs Coverage across All Waking Hours

Jain R, et al. Prim Care Companion CNS Disord. 2017;19(5):17nr02153.

Organize kids for school

Adjusting Medication

• Some patients report a need for additional medication at specific times

– Stimulant dose may be increased when there is a need for increased focus

– Patients who need evening treatment may benefit from

• Combination of extended-release and immediate-release stimulant

• Atomoxetine or a combination of atomoxetine and a daytime stimulant

Adler LA, et al. Curr Psychiatry Rep. 2006;8(5):409-415. Hazell P. CNS Drugs. 2007;21(1):37-46.

Stimulants may be prescribed in combination with a

nonstimulant to ensure coverage into the evening

Extended-release stimulants, lisdexamfetamine, MPH transdermal system

Atomoxetine, bupropion, tricyclic antidepressant

0800 1200 1600 2000 2400Time (h)

Combination treatment: long-acting stimulant and nonstimulant

Long-acting stimulant Immediate-release stimulant

Morning Evening

Long-acting stimulant

Long-acting stimulant (1/2 AM dose)

Medication Dosing Options

Adapted from Hazell P. CNS Drugs. 2007;21(1):37-46.

Managing Common Side Effects

*The use of these medications for this indication is off-label.

Pliszka SR. J Am Acad Child Adolesc Psychiatry. 2006;46(7):894-921. Daughton J, et al. In: Martin A, et al (Eds). Pediatric Psychopharmacology: Principles and Practice.Second Edition. New York, NY: Oxford Press; 2011. Weiss MD, et al. J Am Acad Child Adolesc Psychiatry. 2006;45(5):512-519. Tjon Pian Gi CV, et al. Eur J Pediatr. 2003;162(7-8):554-555. Kratochvil CJ, et al. J Am Acad Child Adolesc Psychiatry. 2005;44(5):499-501. Palumbo DR, et al. J Am Acad Child Adolesc Psychiatry. 2008;47(2):180-188. Hazell PL, et al. J Am Acad Child Adolesc Psychiatry. 2003;42(8):886-94. The Tourette’s Syndrome Study Group. Neurology. 2002;58(4):527-536.

Appetite Loss Insomnia* Stomachaches Tics*

• Patience

• Usually improves

after a few days

• Eat a big breakfast and

delay dinner

• Adjust timing of

medication

• Adjust timing of meals

• Encourage snacks

(including bedtime)

• Consider changing

dose, regimen, or

medication

• Melatonin

• Clonidine, guanfacine

• Trazodone

• Mirtazapine

• Antihistamine (acutely)

• Tricyclic antidepressant

• Direct vs indirect effect

• Medication vs hunger

• Determine time of day

• Patience

• Often resolve after

the first few days of

treatment

• Lower daily dose

• Try a different medication

• Stimulant-exacerbated tics

• Examine severity of tics

• Re-challenge to examine if

tics are stimulant-induced

• Switch to atomoxetine, α2-

adrenergic agonists, or

atypical or typical

antipsychotics (pimozide –

FDA approved)

• Combination therapies

• Atomoxetine plus

stimulant

• Clonidine plus MPH (3

studies)

• Atypical plus other

treatment

Past-Year and Past-Month Prescription Stimulant Nonmedical Use Increases Through Adolescence to Young Adulthood, NSDUH

NSDUH 2017 provides data about the subtypes of prescription stimulants for past-year NMU; for past-year NMU, 95% are prescription stimulants that are primarily prescribed for the treatment of ADHD. The percentage of prescription stimulants prescribed for treatment of ADHD vs other uses is not available for past-month use data. NMU = nonmedical use; NSDUH = National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality. 2017 National Survey on Drug Use and Health: Detailed Tables. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2018. www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHDetailedTabs2017/NSDUHDetailedTabs2017.pdf. Accessed March 14, 2019.

4.6 4.75.5

8.4 8.3

11.0 10.7

13.5

17.0 16.617.7

14.1

15.5

12.9

0.2 0.6 0.92.0 2.2

4.8 5.16.0

8.69.8 9.6

7.3 7.5

5.8

0.0 0.1 0.3 0.7 0.71.1 1.5

2.3 2.02.8 2.4 2.0 2.0 1.9

0

2

4

6

8

10

12

14

16

18

20

12 13 14 15 16 17 18 19 20 21 22 23 24 25

Esti

mate

d P

revale

nce (

%)

Any past-year use

Past-year prescription stimulant NMU

Past-month prescription stimulant NMU

Age (years)

Prescription stimulant data include AMPH, MPH, and prescription

stimulants used for weight loss or conditions such as sleep apnea or narcolepsy

Nonmedical Use of Prescription Stimulants

Prescription stimulant NMU among various age groups

– 5817 of 183,188 adolescents (3%) in 6 studies

– 5490 of 34,683 college students (16%) in 12 studies

– 8451 of 134,063 adults(6%) in 4 studies

Faraone SV, et al. J Am Acad Child Adolesc Psychiatry. 2018; Submitted. Chen LY, et al. Addict Behav. 2015;49:1-6. McCabe SE, et al. J Am Acad Child AdolescPsychiatry. 2013;52(12):1272-1280. McCabe SE, et al. Drug Alcohol Depend. 2016;163:55-63. McCabe SE, et al. J Am Acad Child Adolesc Psychiatry. 2017;56(3):226-233.e4. Chen LY, et al. Addict Behav. 2014;39(5):829-836. Williams RJ, et al. Am J Addict. 2004;13(4):381-389. Arria AM, et al. Pharmacotherapy. 2008;28(2):156-169. Arria AM, et al. Addict Behav. 2013;38(3):1643-1650. Babcock Q, et al. J Am Coll Health. 2000;49(3):143-145. Dupont RL, et al. Am J Addict. 2008;17(3):167-171. Egan KL, et al. Drug Alcohol Depend. 2013;131(1-2):71-77. Garnier-Dykstra LM, et al. J Am Coll Health. 2012;60(3):226-234. Holt LJ, et al. Subst Use Misuse. 2018;53(7):1068-1075. Kinman BA, et al. Subst Use Misuse. 2017;52(10):1256-1265. Phillips EL, et al. Center for the Study of Student Life, The Ohio State University. Columbus, Ohio. 2018. Rabiner DL, et al. J Atten Disord. 2009;13(3):259-270. Tuttle JP, et al. Acad Psychiatry. 2010;34(3):220-223. Wasserman JA, et al. J Am Osteopath Assoc. 2014;114(8):643-653. Cassidy TA, et al. J Atten Disord. 2015;19(7):630-640. Novak SP, et al. Subst Abuse Treat PrevPolicy. 2007;2:32. Upadhyaya HP, et al. Am J Addict. 2010;19(6):569-577.

Patient Education RE: Sharing/Diversion

• Medical risks of others using stimulants

• Ethical risks

• Legal risks

– It’s against the law

– Risk of suspension or expulsion from school

– Risk of dismissal from work

• Prevention

– Don’t let others know you take stimulant medication

– Keep medication in lock box or safe

– Don’t get in the habit of leaving pills around

Rostain AL. Misuse and Abuse of Stimulant Medications Among College and University Students. Presented at: CADDRA 10th AnnualMeeting; October 15, 2013; Montreal, Canada.

Clinical Strategies

• Keep track of pills and refills

• Use extended-release formulations or nonstimulants

• Obtain urine toxicology frequently

• Discuss safe storage and not sharing medications

• Red Flags

– Demand for immediate-release stimulants

– Repeatedly discordant pill counts

– Frequently lost prescriptions

– Requests to increase dosage

Rostain AL. Misuse and Abuse of Stimulant Medications Among College and University Students. Presented at: CADDRA 10th AnnualMeeting; October 15, 2013; Montreal, Canada.

Highlighting Best Practices for Long-Term ADHD Patient Follow-up

Case 1: Heather

• 13-year-old adopted girl with inattentive ADHD and moodiness/irritability

• Virtually no response to MPH at doses up to 30 mg bid

• Increasing conflicts between patient and her parents RE: autonomy issues (talking on the phone, chores, privileges, homework completion)

• New onset of peer difficulties (ie, intense arguments with friends, jealousy towards classmates, exclusion by certain friends from social events)

• Poor response to medication due to clandestine nonadherence; parents discovered a cache of pills under the living room couch cushions

• Heather admitted she was concerned that medication would stunt her growth

Use your keypad to answer now!

What would be your next step in this case?

A. Evaluate patient for possible mood disorder, including depression and bipolar

B. Talk with patient about her insecurities regarding her small stature

C. Talk with parents about the importance of monitoring patient’s adherence

D. Switch patient to nonstimulant medication

E. Hold family session to discussion treatment options

Case 1: Heather

• Clinical Assessment

– Heather continues to exhibit signs/symptoms of ADHD, which is impairing her academic and social functioning

– She does not perceive any benefit of IR MPH and believes it will adversely affect her growth

• Clinical Decision-Making

– Switched regimen from IR MPH to ER formulation

• Patient and Family Education

– Explained the importance of open communication and collaborative problem-solving to address concerns and issues

– Addressed issues of efficacy and adverse effects with change in medication

– Recommended family-oriented CBT to address developmental issues

CBT = cognitive-behavioral therapy.

Case 2: Charlie

• 18-year-old college freshman with combined ADHD and mild dyslexia• Complaining of sleep problems, irritability, anxiety, and worsened

concentration– Diagnosed and treated throughout elementary and high school with

MAS IR– Granted extended time for tests and writing assignments in college– Assigned an ADHD coach at school’s learning center

• Failed 2 courses first semester; placed on academic probation– Didn’t make use of accommodations, never went to learning center,

missed class• Admits he “adjusted” his medication (increased dose, took it late at

night, etc.) • When asked about sharing his medication with other students, Charlie

replied, “Everybody does it, it’s no big deal…”

Use your keypad to answer now!

What would be your next step in this case?

A. Switch patient to a nonstimulant medication

B. Switch patient to a long-acting stimulant medication

C. Educate patient regarding his nonmedical stimulant use behaviors

D. Recommend patient go to academic resources center for help

Case 2: Charlie

• Clinical Assessment – Patient demonstrates signs of treatment nonadherence and of NMU– He is not taking advantage of learning accommodations and school

services• Clinical Decision-Making

– Switched regimen from IR MAS to lisdexamfetamine with clear contingency plan

• Patient Education– Clarified he is engaged in NMU, which carries medical and legal

consequences– Expressed concern that his actions are risking physical and mental health

as well as jeopardizing his chances for success in college– Emphasized importance of academic coaching and of using

accommodations – Recommended patient start CBT

Practical Take-Aways

• ADHD is a complex, heterogeneous, genetically determined

neurodevelopmental lifespan disorder that is optimally treated with

combined medical and psychosocial approaches

• Adherence to treatment can be improved by establishing a close

collaborative relationship, monitoring treatment efficacy, looking for

problems with tolerability, and educating about risks of misuse

• Stimulants are the most effective medications for ADHD across the

lifespan; they can be prescribed safely and appropriately by using

established treatment guidelines

therapeutic advances and follow-up strategies …...therapeutic advances and follow-up strategies...

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