Attention Deficit/

Hyperactivity
Disorder
Molly Rincavage, PharmD
Objectives

1. Recognize the pharmacology of medications

used to manage ADHD
2. Select a treatment plan for ADHD that
considers patient and agent related
variables
3. Identify an appropriate monitoring plan for
a patient with ADHD, including how to
mitigate adverse effects
Outline

•Review
•Mechanism of Action
•Formulations
•Adverse Effects, Precautions, Contraindications,
Black Box Warnings
•Treatment Guidelines
•Monitoring
•Patient Case
Review
Review

Which of the following is not a core symptom of

ADHD?
A.Inattention
B. Hyperactivity
C. Defiance
D.Impulsivity
Review

True or False: ADHD occurs predominantly

in young, female individuals
Review

Which of the following is not a common comorbidity

in patients with ADHD?
A.Disruptive behavior disorder
B. Hyperthyroidism
C. Mood disorder
D.Anxiety disorder
Mechanism
of
Action
Pharmacologic Classes

Stimulants
• Methylphenidates
• Methylphenidate
• Dexmethylphenidate
• Amphetamines
• Dextroamphetamine
• Levoamphetamine
• Lisdexamfetamine

Non-stimulants
• Selective norepinephrine reuptake inhibitors
• Atomoxetine
• Alpha-2 agonists
• Guanfacine
• Clonidine
Stimulants

• Amphetamines and
methylphenidates
• Block the reuptake of
norepinephrine and
dopamine into the
presynaptic neuron, thus
increasing the
concentrations of these
monoamines in the
extraneural space
Non-stimulants

• Atomoxetine
• Selective norepinephrine
reuptake inhibitor
• Inhibits reuptake of
norepinephrine, thus
increasing concentration in
synaptic cleft
Non-stimulants

• Guanfacine and clonidine

• Alpha 2-adrenergic
receptor agonists
• Increase noradrenergic
tone in prefrontal cortex by
stimulating postsynaptic
alpha-2A receptors
Formulations
Medication Administration at School

ADHD affects a largely pediatric population, which often requires

coverage throughout the school day

There is a stigma associated with taking medication at school

Medication Authorization Form

• Completed by the parent which authorizes the school nurse to
give child medication
• Completed by the practitioner to provide information on the
diagnosis, medication, time, dosage to be dispensed, and
possible side effects
Plasma Concentration Time Profile
 Amphetamine Formulations
Formulation Brand Name Available Dosage Duration of Frequency
Forms Action (hours)
Mixed Immediate- Adderall 5, 7.5, 10, 12.5, 15, 20, 4-6 1-3 times daily
release (IR) salts 30 mg tablets

Amphetamine Evekeo 5, 10 mg tablets 4-6 1-3 times daily

sulfate IR
Dextroamphetamine Dexedrine 5, 10 mg tablets 4-6 1-3 times daily
IR
Dextroamphetamine ProCentra 1 mg/ml 4-6 1-3 times daily
IR liquid
 Amphetamine Formulations
Formulation Brand Name Available Dosage Forms Duration of Frequency
Action (hours)
Dextroamphetamine Extended- Dexedrine Spansule 5, 10, 15 mg capsules 6-8 Daily
release (ER)
Lisdexamfetamine Vyvanse 20, 30, 40, 50, 60, 70 mg 10-12 Daily
capsules
Mixed Extended-release (XR) Adderall XR 5, 10, 15, 20, 25, 30 mg 10-12 Daily
salts capsules
Amphetamine sulfate XR Adzenys-XR- ODT 3.1, 6.3, 9.4, 12.5, 15.7, 18.8 12 Daily
orally disintegrating tablet mg tablets

Amphetamine sulfate XR Dyanavel XR 2.5 mg/ml 12 Daily

suspension
Mixed Extended-release (XR) Mydayis 12.5, 25, 37.5, 50 mg 16 Daily
salts capsules
 Methylphenidate Formulations

Formulation Brand Name Available Dosage Duration of Frequency

Forms Action (hours)
Immediate-release (IR) Methylin 5, 10, 20 mg tablets 3-6 1-3 times daily
Ritalin
Dexmethylphenidate IR Focalin 2.5, 5, 10 mg tablets 3-6 1-3 times daily
Extended release (ER) Metadate ER 20 mg tablet 6-8 Daily
Sustained release (SR) Ritalin SR 20 mg capsules 6-8 Daily
Long-acting (LA) Ritalin LA 20, 30, 40 mg capsules 6-8 Daily
Controlled delivery Metadate CD 10, 20, 30, 40, 50, 60 mg 6-8 Daily
(CD) capsules
 Methylphenidate Formulations
Formulation Brand Name Available Dosage Duration of Frequency
Forms Action (hours)
Dexmethylphenidate XR Focalin XR 5, 10, 15, 20 mg 8-12 Daily
capsules
Transdermal patch Daytrana 10, 15, 20, 30 mg 8-10 Daily
patches
Osmotic release oral system Concerta 18, 27, 36, 54 mg 10-12 Daily
(OROS) capsules
Methylphenidate XR orally Contempa-XR- ODT 8.6, 17.3, 25.9 mg 12 Daily
disintegrating tablet tablets
Extended release multilayer Aptensio XR 10, 15, 20, 30, 40, 50, 12 Daily
bead (MLR) 60 mg capsules
Extended-release (XR) Quillivant XR 5 mg/ml 12 Daily
suspension
Extended-release (ER) Quillichew ER 20, 30, 40 mg tablets 12 Daily
chewable tablet
 Non-stimulants

Medication Brand Available Duration Frequency Notes

Name Dosage of Action
Forms (hours)
Atomoxetine Strattera 10, 18, 25, 12-24 1-2 times Dosed by weight
40, 60, 80, daily Takes 4-6 weeks to
and 100 mg see response
capsules
Clonidine extended- Kapvay 0.1, 0.2 mg 12-24 1-2 times Takes 2-4 weeks to
release tablets daily see response
Guanfacine Intuniv 1, 2, 3, 4 mg 24 Daily Dosed by weight
extended-release tablets Takes 2-4 weeks to
see response
 Wax Matrix

Formulations:
● Metadate ER
● Ritalin SR
 Multilayer Extended Release Bead

Formulations:
● Aptensio XR
 DiffuCaps and SODAS

Formulations:
● Ritalin LA
● Focalin XR
● Adderall XR
● Metadate CD
● Mydayis
 Osmotic Release Oral System (OROS)

Formulations:
● Concerta
 Prodrug

Formulations:
● Vyvanse
 LiquiXR

Formulations:
● Dyanavel
 XR-ODT

Formulations:
● Adzenys
● Contempla
Administration Instructions

Immediate release tablets

• May crush

Extended release tablets

• Do not crush or chew

Extended release capsules

• Do not crush or chew. Capsules may be opened and contents
sprinkled on food (ex: applesauce).
Administration Instructions

Patch
• Apply to hip 2 hours before effect is needed and remove up to
9 hours after application. Effects persists for 1-3 hours after
removal.
Suspension
• Shake vigorously for 10 seconds before administration

Orally disintegrating tablet

• Place tablet on top of tongue and allow to dissolve
 Adverse Effects,
Precautions,
Contraindications,
Black Box Warnings
Stimulants

Adverse Effects
•Common
•Decreased appetite, delayed growth, insomnia,
headache, irritability
•Rare
•Hypertension, tachycardia, tics, psychosis, mania,
priapism, peripheral vasculopathy
Stimulants

Precautions

•Bipolar disorder, anxiety, seizure disorder

Contraindications

• History of substance abuse, hyperthyroidism,

cardiovascular disease, circulatory disorders,
uncontrolled hypertension, glaucoma, tics, MAOI use
within 14 days
Stimulants

Black Box Warnings

•Use has been associated with serious cardiovascular
events including sudden death in patients with
preexisting structural cardiac abnormalities or other
serious heart problems
•Stimulants have high potential for abuse and
dependence. Administration for prolonged periods may
lead to drug dependence and must be avoided. Assess
the risk of abuse prior to prescribing and monitor for
signs of abuse and dependence while on therapy
Atomoxetine

Adverse effects
• Common
•Headache, nausea, vomiting, dry mouth, insomnia,
somnolence
• Rare
•Tachycardia, hypertension, priapism, hepatotoxicity,
psychosis, mania
Atomoxetine

Precautions
• Bipolar disorder, uncontrolled hypertension, hepatic
impairment
Contraindications
•Severe cardiovascular disease, glaucoma,
pheochromocytoma, MAOI use within 14 days
Black Box Warning
•Atomoxetine increases the risk of suicidal ideation in
studies in children and adolescents with ADHD
Guanfacine and Clonidine

Adverse Effects
• Somnolence, hypotension, bradycardia
• Taper when discontinuing to prevent rebound
hypertension

Precautions
• Hypotension, bradycardia, heart block
• Operating heavy machinery
Drug/Food and Drug/Drug Interactions

High fat meals

• Delay time to peak concentration of extended release
stimulants
Acidic foods
• Decrease absorption and increase excretion of immediate
release stimulants
Acid suppressing medications (PPIs, H2RAs, antacids)
• Increase absorption and decrease excretion of immediate
release stimulants
Drug/Drug Interactions

Monoamine oxidase inhibitors

• Concurrent use with stimulants or atomoxetine can result in
hypertensive crisis

CNS depressants
• May enhance sedative effect of alpha-2 agonists

CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion, quinidine)

• May require decreased dose of atomoxetine
Treatment
Guidelines
AAP Treatment Guidelines

Preschool-aged children (4 –5 years of age)

• 1st line
• Behavior therapy

• 2nd line
• Methylphenidate IR
• Off label, but evidence to support its use in
moderate to severe dysfunction if patient fails
behavior therapy
AAP Treatment Guidelines

Elementary school-aged children (6-11 years of age)

• 1st line
• Methylphenidate or amphetamine +/- behavior
therapy
• 2nd line
• Atomoxetine, guanfacine ER, or clonidine ER
+/- behavior therapy
AAP Treatment Guidelines

Adolescents (12-18 years of age)

• 1st line
• Methylphenidate or amphetamine +/- behavior
therapy
• 2nd line
• Atomoxetine, guanfacine ER, or clonidine ER
+/- behavior therapy
ADHD Treatment in Adults

• Stimulants and atomoxetine are FDA approved

for use in adults
• Weak evidence for guanfacine ER and clonidine
ER
Non-pharmacologic Therapy

Caregiver education
• Structured schedule
• Positive and negative reinforcement

Classroom modifications
• Individualized education plans
• Small classrooms
• Work/test modifications

Social skills training

• Learn teamwork
Medication Selection

Patient related variables

• Patient preferences
• Age
• Comorbidities
• Risk of abuse
• Patient ability to swallow pills

Agent related variables

• Onset, peak, duration
• Frequency of dosing
• Adverse effects
• Expense
Medication Selection

Personal or family history of substance abuse

• Vyvanse (prodrug), Concerta (OROS), Daytrana
(patch), atomoxetine, guanfacine, clonidine

Uncontrolled hypertension, structural cardiac

abnormality, cardiomyopathy, heart murmur,
arrhythmia
• Guanfacine, clonidine
Medication Selection

Depression
• Stimulants, guanfacine, clonidine

Bipolar disorder, tics

• Guanfacine, clonidine
Medication Selection

Difficulty swallowing pills

• Daytrana (patch), Dyanavel (liquid),
Quillichew (chewable), Quillivant (liquid),
Procentra (liquid), Adzenys (ODT), Contempla
(ODT), crush immediate release

Difficulty affording medications

• Immediate release, generics
Dosing

• Start at lowest dose and titrate on a 7-day basis

• Young children have slower metabolism so should
be started at a lower dose that is increased in smaller
increments
• When converting from one formulation to another,
not a 1:1 conversion
Dosing

Atomoxetine
Dosing

Guanfacine ER
Monitoring
Indices of Therapeutic Effect

• Improvement in core symptoms

• Improvement in family and peer relationships
Rating Scales

Conners’ Rating Scale

•Used clinically and in clinical trials
•Parent-rated version (full length 110 items, abbreviated 43 items)
and teacher-rated version (full length 115 items, abbreviated 39
items)
•Items scored 0 (never) to 3 (very often)
•Raw score converted to percentile indicative of ADHD
•Scales for inattentive, hyperactive-impulsive, and combined
subtypes of ADHD
•Screens for oppositional defiant disorder and conduct disorder
Monitoring

Efficacy Safety
• Rating scales • HR • Appetite
• School • BP • Mood
performance • Height • EKG if
• Weight history of
• Sleep cardiac
disease
Managing Adverse Effects

Insomnia
• Take earlier in day, switch to shorter duration, use
medication for sleep

Reduced appetite
• High calorie meals at lowest effect of medication
(early morning, late evening)

Nausea/vomiting
• Take with food, reduce dosage
Managing Adverse Effects

Rebound symptoms
• Add dose in afternoon,
change time of second dose,
change to longer
formulation

Delayed growth (crosses two

major percentile lines)
• Reduce dosage, drug
holiday, alternative therapy
Managing Adverse Effects

Cardiovascular (change in BP ≥15 mmHg or HR ≥20 bpm)

• Reduce dosage, alternative therapy

Irritability
• Reduce dosage, assess for comorbidities

Tics
• Reduce dosage, alternative therapy

Psychiatric disorder
• Discontinue medication, alternative therapy
Follow-Up

• A follow-up visit is recommended 1 month after initiation to monitor for

safety and efficacy
• Visits can then occur on a monthly basis until there is a consistent
optimal response, and then every 3 months
• Need for continued use should be assessed every 12 months
•Continue as long as symptoms are present and cause functional
impairment
•If patient is on a stimulant, consider drug holidays during vacations,
weekends, summer
Response

Maximum
Dose?
No Yes
Titrate to
maximum Response?
dose

Partial None

Switch to
Add non-stimulant other
stimulant class

If still no
response,
switch to non-
stimulant
Patient Case
Patient Case

Peter is an 8 year old male who was recently

diagnosed with ADHD, with a predominantly
hyperactive-impulsive presentation. His personal
history is unremarkable. He has a family history
of diabetes, MI, and colon cancer. What class of
medications would you recommend as initial
therapy?
Patient Case

Peter arrives to school at 8:00AM. His teachers report his symptoms

affect his ability to complete his work at school. Peter’s parents
state that the symptoms then persist when he does homework after
school, which takes until 4:00PM. Peter’s parents are worried
about being able to afford his medication. Which of the following
therapies would you recommend for Peter?

A. Ritalin (methylphenidate) LA 20 mg every morning

B. Amphetamine salts IR 5 mg in the morning and at lunch
C. Vyvanse (lisdexamphetamine) 20 mg every morning
D. Daytrana (methylphenidate) 10 mg patch daily
Patient Case

Peter is initiated on the recommended

therapy. He returns for a follow up visit in
one month. What pertinent information
would you want to assess as part of your
monitoring plan?
Patient Case

Over the course of 6 months, Peter is titrated to the maximum dose

of Adderall. Peter’s score on the Conners Scale has improved by
25%. His parents feel that Peter’s symptoms have improved, but
still interfere with his ability to complete his schoolwork. What
changes, if any, would you recommend to his regimen?

A. Switch to a methylphenidate product

B. Switch to clonidine ER 0.1 mg daily
C. Add guanfacine ER 1 mg daily
D. No changes are necessary at this time
Questions?
mrincava@su.edu
 References

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http//www.chadd.org
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