Attention Deficit Hyperactivity Disorder (ADHD)

what is the most common neurobehavioral disorder amongst children and adolescent

ADHD

why are boys more likely than girls to be diagnosed with ADHD

boys often present with symptoms of hyperactivity while girls present more with inattentiveness and are more likely to go undiagnosed

most noticeable symptom of ADHD for: preschoolers

hyperactivity

most noticeable symptom of ADHD for: school age

inattentiveness

most noticeable symptom of ADHD for: adolescents/college/adults

less hyperactivity —> more restlessness

what is the most common reason for developing ADHD

genetics (75% heritable)

what are uncommon risk factors for developing ADHD

low birth weight/premature

prenatal exposure: nicotine, alcohol, acetaminophen

traumatic brain injury

lead and toxin exposure at young age

Patients with ADHD showed delayed development of what by 2-3 years

Prefrontal cortex

function of prefrontal cortex

attention

problem solving

impulse control

emotional regulation

ADHD is affected by which neurotransmitters

deficiency in dopamine + norepinephrine

functions of norepinephrine and dopamine in ADHD

maintain attention

regulate mood

resist distractions

effects of too much or too little norepinephrine and dopamine

too much = fatigued

too little= stressed

• distracted

• disorganized

• forgetful

• impulsive

effects of maintaining a good balance of norepinephrine and dopamine

focused

organized

responsible

Diagnostic criteria of ADHD: persistent pattern of inattention and or hyperactivity impulsivity

• Present for 6+ months

• Present in 2+ settings (home & school)

• Present before age 12

patients younger than 18 must present with how many symptoms of ADHD

6

patients older than 18 must present with how many symptoms of ADHD

5

9 inattentive symptoms of ADHD

fails to give close attention to details/makes careless mistakes

difficulty sustaining attention

does not seem to listen

does not follow instructions

difficulty organizing

avoids or dislikes tasks that requires sustained efforts

often loses things

easily distracted

forgetful

9 hyperactive/impulsive symptoms of ADHD

fidgets/squirms in seat

leaves seat when remaining seated is expected

turns about and climbs (adults = restlessness)

unable to play or engage in activities quietly

“on the go” or “driven by a motor”

talks excessively

blurts out answers

difficulty waiting turn

interrupts or intrudes on others

standard of care for young patients with ADHD

behavior management therapy

• parent training in behavior management

• behavioral classroom intervention

Stimulant drugs used for ADHD

controlled II

methylphenidate

amphetamines

Non-Stimulants used for treatment of ADHD

Norepinephrine Reuptake Inhibitors

• Atomoxetine

• Viloxazine

Alpha-2 Agonists

• Clonidine

• Guanfacine

Off label non-stimulants used to treat ADHD

• Bupropion

• Modafanil

• TCAs (imipramine or nortriptyline)

What class of medications is most effective for the treatment of ADHD

stimulants

Are methylphenidates or amphetamines more effective

equally effective- fail one agent, switch to the other class

Preschoolers (4-5 years old) treatment options for ADHD

First line: behavior therapy

Second line: stimulant (methylphenidate preferred)

which population is methylphenidate preferred for the treatment of ADHD

preschoolers- age 4-5

Elementary (6-11) + Adolescent (12-18) treatment options for ADHD

Behavior therapy + Stimulant

• behavior therapy alone not recommended- may not be as effective in older patients

• either amphetamines or methylphenidates can be used

Dose limiting side effects of stimulants

decreased appetite

insomnia

how to reduce appetite loss seen when taking stimulants for ADHD

large meal in morning before effect of drug kicks in

large meal for dinner once drug wears off

how to reduce insomnia seen when taking stimulants for ADHD

do not give dose too late or use a shorter acting agent

how to reduce anxiety seen when taking stimulants for ADHD

reduce dose or use extended release

how to reduce stomach upset seen when taking stimulants for ADHD

take with food

how to reduce irritability seen when taking stimulants for ADHD

extended release formulation

true or false: every patient receiving a stimulant should receive a baseline ECG before initiating therapy

false- not routinely recommended

which patient population should receive a baseline ECG before initiating stimulants

family history of cardiac abnormalities or sudden death

abnormal cardiac findings on physical exams (heart murmur)

what is the preferred stimulant for patients less than 4-5

methylphenidate

Methylphenidate immediate release duration of action

3-6 hours

Methylphenidate immediate release dosing

2-3x/day

advantages to taking immediate release methylphenidate

easier to titrate for kids

lower risk of insomnia

may add as an afternoon dose to long acting stimulants

how should immediate release methylphenidate be taken

empty stomach

disadvantages to immediate release methylphenidate

short duration

rebound irritability

Methylphenidate extended release duration

Metadate ER or Ritalin SR tablet= 3-8 hours

bead filled capsule= 6-9 hours

Aptensio XR= 12 hours

which extended release form of methylphenidate needs to be swallowed whole

metadate sr or ritalin er tablets

which extended release form of methylphenidate needs to be taken on an empty stomach for optimal absorption

metadate sr or ritalin er tablets

which extended release form of methylphenidate can be opened and sprinkled onto applesauce

Metadate CD/Ritalin LA bead filled capsules (do not chew bead)

Aptensio XR

Jornay

Azstarys

benefits to using extended release methylphenidate

does not require midday dosing when the child is in school

some can be opened and sprinkled on applesauce or yogurt

disadvantages to using extended release methylphenidate

insomnia if medication is dosed later in the day

some may not last the entire day

what is the most commonly prescribed methylphenidate

OROS methylphenidate

mechanism of action for OROS methylphenidate

triphasic release= stimulate three times a day dosing

OROS methylphenidate stands for

osmotic controlled release oral system

duration of action OROS methylphenidate

10-12 hours

counseling point for OROS methylphenidate

• pellet will come out in stool but it’s just the casing and does not contain any medication

• do not crush, chew, or manipulate in anyway

advantages to OROS methylphenidate

true once daily dosing

lower abuse potential

disadvantages to OROS methylphenidate

expensive + medication shortages

which stimulants are available as a transdermal patch

methylphenidate

dextroamphetamine

which patient population is the methylphenidate transdermal patch indicated for

Children (6-17 years old)

how long does it take for methylphenidate patch to start working

2 hours (place patch on child before they wake up)

How long does the effect of methylphenidate transdermal patch last after removing the patch

additional 3 hours

what is the overall total duration for the methylphenidate transdermal patch

10-12 hours

advantages to using the methylphenidate transdermal patch

customize the duration by varying the wear time

minimal GI upset

disadvantages to using the methylphenidate transdermal patch

low compliance- especially in children

insomnia if patch is not removed early enough

erythema (redness) and irritation

Alternative Extended Release Methylphenidate Formulations: duration of action

Oral suspension

Chewable Tablet

ODT (orally disintegrating tablet)

Oral suspension: 8-12 hours

Chewable Tablet: 8-12 hours

ODT (orally disintegrating tablet): up to 12 hours

brand name of a specially designed extended release capsule for methylphenidate

Jornay PM

Jornay PM is useful for which patient population

struggles with early morning symptoms of ADHD

Jornay PM Dosing

Administer the night before in evening (6:30-9:30 pm)

Jornay PM MOA

taken in the evening the night before

• outer capsule takes 10 hours to dissolve to prevent release of medication

• inner capsule provides extended release of the medication thoughout the day

Jornay PM administration

contains bead filled capsule that can be opened and sprinkled on applesauce

duration of action for dexmethylphenidate immediate release

3-6 hours

duration of action for dexmethylphenidate extended release

8-12 hours

Azstarys generic form

serdexmethylphenidate + dexmethylphenidate

Azstarys duration of action

10-13 hours

Azstarys MOA

serdexmethylphenidate= prodrug

dexmethylphenidate= more active isomer

(able to give a longer duration of action)

amphetamines mechanism of action

blocks reuptake of norepinephrine and dopamine

enhances release of norepinephrine and dopamine

how does methylphenidate differ from amphetamines in their mechanism of action

amphetamines are also able to enhance the release of dopamine and norepinephrine

methylphenidate can only inhibit the reuptake

is methylphenidate or amphetamines more potent

amphetamines

dextroamphetamine duration of action:

immediate release tablet

sustained release bead capsule

immediate release liquid

immediate release tablet: 4-6 hours (bid-tid)

sustained release bead capsule: 6-10 hours (daily-bid)

immediate release liquid: 4-6 hours (bid-tid)

how should dextroamphetamine transdermal patch be applied

2 hours before effect is needed

when should dextroamphetamine transdermal patch be removed

within 9 hours of use

what is the most commonly prescribed form of amphetamine

mixed amphetamine salts (adderall)

mixed amphetamine salts duration of action (immediate release vs extended release)

Adderall immediate release: 4-8 hours (daily-tid)

Adderall XR: 8-12 hours (once daily)
Evekeo: 4-6 hours

Mydayis TM: 16 hours

which amphetamine salt is a mix of dextro and levoamphetamine

adderall immediate release

dextroamphetamine has more activity of which neurotransmitter

more dopamine than norepinephrine activity

which mixed amphetamine salt is available in ODT form

evekeo

which amphetamine salt it long acting, triple bead

mydaisTM

which amphetamine salt is immediate release, single salt, 1:1 ration of dextro + levoamphetamine

Evekeo

which is the longest acting mixed amphetamine salt

MydayisTM

Extended release amphetamine drugs: oral suspension

Dyanavel XR

Extended release amphetamine drugs: oral disintegrating tablet

Adzenys

Dyanavel XR duration of action

8-13 hours (extended release oral suspension)

Adzenys duration of action

9-12 hours (extended release oral disintegrating tablet)

prodrug of dexamphetamine

lisdexamphetamine

Lisdexamphetamine MOA

pro-drug requires activation via hydrolysis

lisdexamphetamine duration of action

10-12 hours (may be delayed 2-3 hours)

why may there be a delay of duration for lisdexamphetamine

requires hydrolysis to become active (may be delayed 2-3 hours)

which stimulant used in the treatment of ADHD is also approved for moderate-severe binge eating disorder in adults

lisdexamphetamine

why does lisdexamphetamine have a lower potential for abuse

slow onset of action

advantages for using lisdexamphetamine

once daily dose

less abuse

can sprinkle capsule in water/yogurt/juice

chewable formulation available

disadvantages to lisdexamphetamine

expensive

delayed onset of action

why are all stimulants controlled and what level are they

schedule II

• euphoric effects

• performance enhancing effects

which stimulants have less misuse potential

OROS methylphenidate

methylphenidate

lisdexamphetamine