therapeutic advances and follow-up strategies …...therapeutic advances and follow-up strategies...
TRANSCRIPT
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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.
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Faculty Disclosure
• Dr. Rostain: Royalties—Routledge/Taylor Francis Group, St. Martin’s Press; Scientific Advisory Board—Shire/Takeda, Arbor Pharmaceuticals.
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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.
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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
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Brief Overview of ADHD
What the Science Says
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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.
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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.
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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
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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
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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
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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
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ADHD Treatment across the Lifespan
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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
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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
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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
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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)
Post-diagnosis of ADHD
• 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
Post-diagnosis of ADHD
• 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
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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 or Nonresponse
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
Partial Response or Nonresponse
Partial Response or Nonresponse
Partial Response or Nonresponse
Partial Response or Nonresponse
Partial Response or Nonresponse
Stimulant not used in Stage 1
Atomoxetine
Any stage(s) can be skipped
depending on the clinical picture
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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.
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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)
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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.
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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
Rostain AL. Improving Treatment Adherence of Patients with ADHD. Presented at: CADDRA 13th Annual Meeting; October 29, 2017; Quebec City, Canada.
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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
Rostain AL. Improving Treatment Adherence of Patients with ADHD. Presented at: CADDRA 13th Annual Meeting; October 29, 2017; Quebec City, Canada.
• 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
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Evaluating Current Stimulant Formulations
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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
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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
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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.
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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
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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
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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
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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
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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
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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
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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.
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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.
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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
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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
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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.
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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.
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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.
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Highlighting Best Practices for Long-Term ADHD Patient Follow-up
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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
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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
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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.
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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…”
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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
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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
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Practical Take-Aways
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• 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