Attention Deficit/
Hyperactivity Disorder
J. Hancey, PhD, MD
Dept. of Psychiatry
OHSU
Key Features of ADHD
• Cognitive
• Motor
• Behavioral
Cognitive Features of ADHD
• Inattention, distractibility, loss of focus,
wandering from task to task
• Task incompletion
• Difficulties with
priorities
Motor Features of ADHD
• Motor hyperactivity
• Constant motion
• Inability to sit at desk, wandering
Behavioral Features of ADHD
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Impulsivity
Thrill-seeking behavior
Risk taking behavior
Irritability
Developmental Features of ADHD:
Adults
Adolescents
Children
Disorganization
Impatience
Inattentiveness
Impulsivity
Boredom
Irritability
Distractible
Shift activities
Aggressive
Low frustration tolerance
Motor hyperactivity
ADHD: “an equal opportunity destroyer”
Impairments:
-academic/occupational
-3 fewer years of education than controls
-social functioning
-substance abuse
-health/injury
-4x serious injury rate, 3x MVA rate
-self-esteem
-sexual behavior
-criminality (estimates: 25-57% of inmates)
-the Colorado experience (recidivisim
cut from 60% to 11%
The Risk of Substance Abuse:
Declines with Treatment
--between ages 15-27 = 47% (vs 15%)
--65% lifetime
Biederman J, et al. Pediatrics, 1999; 104:e20
DSM-IV-TR Diagnosis of
ADHD in Adults
Differential: BAD vs ADHD
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Symptomatic: episodic vs chronic
Decreased need for sleep vs insomnia
Hypersexuality
Grandiosity
Elated mood
Co-morbidity
• OCD
• Tourette’s Syndrome
– a PANDAS phenomenon?
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Learning Disabilities
Conduct Disorder
Sleep disturbances: DFA, morning sedation
Drug/etOH abuse
ODD, CD, ASPD
Sleep Disorders in ADHD
• Sleep disorders common with ADHD at all
ages
– Sleep walking, talking
– DFA (10-15% in young children; 50% at 12.4
years; 75% by age 30
– Restlessness
– Fractured sleep architecture
– enuresis
Corkum, et al. J Am Acad Child Adolesc Psychiatry 1999,38.1285
Sleep Disorders in ADHD (cont)
• 75% of adolescents and adults with ADHD
are “nightowls”—difficulty shutting down
• Once asleep, they experience multiple
awakenings or toss and turn
• Significant difficulty awakening and feeling
mentally alert
• Intrusion of drowsiness when bored
Medications
• Start with stimulant medications
– 80% of patients will respond to stimulants, but
often at lower than recommended doses
– stimulants address the underlying problem of
hypoarousal
– dosage correlates with no known factors--age,
sex, body weight, sx severity--must be
individualized
Extended Release Stimulant
Options
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Concerta: 22% immediate / 78% delayed
Metadate CD: 30% / 70%
Ritalin LA: 50% / 50%
Adderall XR: 50% / 50%
Vyvanse: dextroamphetamine linked to lysine
Absorption may be impaired by citric and ascorbic acid. Avoid citrus
fruit, all fruit juices, most carbonated beverages, breakfast bars,
high vitamin cereals and vitamin C one hour before and after dose.
A simple acid-base reaction may precipitate out the stimulant, thus
precluding absorption.
Long-acting Methylphenidate
Medications
Concerta ®
Metadate® CD
Ritalin® LA
OROS®
Diffucaps®
SODAS™
Dose
18 mg 27 mg 36 mg 54 mg
20 mg
20 mg 30 mg 40 mg
Immediate
release
22%
4 mg 6 mg 8 mg 12 mg
30%
6 mg
50%
10 mg 15 mg 20 mg
Sustained/
2nd release
78%
14 mg 21 mg 28 mg 42 mg
70%
14 mg
50%
10 mg15 mg 20 mg
Products
Formulation
Technology
Concerta® [package insert]. Moutain View, CA: Alza Corporation; 2001. OROS® is a registered trademark of ALZA Corporation.
Metadate® CD [package insert]. Rochester, NY: Celltech Pharmaceuticals, Inc; 2002. Diffucaps ® is a registered trademark of Eurand.
Ritalin® LA [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2002. SODAS ™ is a trademark of Elan Corporation, Plc.
Comparison of Extended-release
Methylphenidate Dosage Forms
Mean d,l-methylphenidate
plasma levels (ng/mL)
20
Ritalin® 20 mg BID
Concerta® 54 mg
Metadate® CD 60 mg (3 x 20 mg)
15
Ritalin® LA 40 mg
10
5
0
0
5
10
Time (h)
Gonzalez MA, et al. Int J Clin Pharmacol Ther. 2002;40:175-184.
Data on file, Novartis Pharmaceuticals.
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Stimulants
• Newer products are refined formulations,
not new drugs.
Absorption impaired by citric and ascorbic acid. Avoid citrus
fruit, all fruit juices, most carbonated beverages, breakfast bars,
high vitamin cereals and vitamin C one hour before and after dose.
A simple acid-base reaction precipitates out the stimulant, thus
precluding absorption.
Adderall®
• Blend of four different salts of amphetamine
• Available generically as MAS
• available as an XR formulation
– Duration of action above baseline about 7.5-8 hrs
– May need bid dosing in adults
Concerta®: a 12 hour MPH
preparation
Metadate® CD (methylphenidate HCl, USP)
Extended-Release Capsules for ADHD
Biphasic Release: Diffucaps®*
Bead-Delivery System
Metadate is a registered trademark of Celltech Pharma, Ltd.
*Diffucaps is a registered trademark of Eurand.
Focalin®: dex-methylphenidate
• The dextro isomer of methylphenidate
• Dose at ½ the dosage of the racemic mixture
Non stimulants with reported
efficacy
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Desipramine
Bupropion
Modafanil/armodafanil
Guanfacine/clonidine
Atomoxetine
Duloxetine
Lisdexamfetamine: Vyvanse®
• Dextroamphetamine linked to lysine sidechain
• Activated when lysine cleaved off by
enzyme on RBC’s
• Duration: 12-14 hours
Drug Choice Considerations
• Duration of action
• Intra-day dosing
• Compliance is generally poor due to
forgetfulness
Stimulant Dosing:
Response
does not correlate
with weight, age, severity of sx.
Dose
Dependence, Addiction and
Abuse
• Dependence?--you betcha!
• Drug addiction?--No. Washes out daily,
without withdrawal.
• Drug abuse?--possible, but rare. People
usually feel worse if overdosed. Report
feeling like a “zombie” or “too amped”:
<0.1% will take excess meds >5x in their lifetime
• Diversion: a huge issue