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

• Impulsivity• Thrill-seeking behavior• Risk taking behavior• Irritability

Developmental Features of ADHD:

Children

Adolescents

Adults DisorganizationImpatienceInattentivenessImpulsivityBoredomIrritabilityDistractibleShift activitiesAggressiveLow frustration toleranceMotor 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

Biederman J, et al. Pediatrics, 1999; 104:e20

--between ages 15-27 = 47% (vs 15%)--65% lifetime

DSM-IV-TR Diagnosis of ADHD in Adults

Differential: BAD vs ADHD

• Symptomatic: episodic vs chronic• Decreased need for sleep vs insomnia• Hypersexuality• Grandiosity• Elated mood

Co-morbidity

• OCD• Tourette’s Syndrome

– a PANDAS phenomenon?

• 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• 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, thusprecluding absorption.

Long-acting MethylphenidateMedications

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.

Products 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

Immediaterelease 4 mg 6 mg 8 mg 12 mg 6 mg 10 mg 15 mg 20 mg

30% 50%

Sustained/2nd release 14 mg 21 mg 28 mg 42 mg 14 mg 10 mg15 mg 20 mg

78% 70% 50%

22%

FormulationTechnology

Ritalin® LA 40 mg

Metadate® CD 60 mg (3 x 20 mg)

Concerta® 54 mg

Time (h)

0 5 10 150

5

10

15

20

Mea

n d,l

-met

hyl

ph

enid

ate

pla

sma

leve

ls (

ng

/mL

)

Comparison of Extended-release Methylphenidate Dosage Forms

Ritalin® 20 mg BID

Gonzalez MA, et al. Int J Clin Pharmacol Ther. 2002;40:175-184.

Data on file, Novartis Pharmaceuticals.

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, thusprecluding 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

• Desipramine• Bupropion• Modafanil/armodafanil• Guanfacine/clonidine• Atomoxetine • Duloxetine

Lisdexamfetamine: Vyvanse®

• Dextroamphetamine linked to lysine side-chain

• 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: does not correlate with weight, age, severity of sx.

Dose

Res

pons

e

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”:

• Diversion: a huge issue<0.1% will take excess meds >5x in their lifetime