1. Attention Deficit/ Hyperactivity Disorder J. Hancey, PhD, MD Dept. of Psychiatry OHSU

2. Key Features of ADHD Cognitive Motor Behavioral

3. Cognitive Features of ADHD Inattention, distractibility, loss of focus, wandering from task to task Task incompletion Difficulties with priorities

4. Motor Features of ADHD Motor hyperactivity Constant motion Inability to sit at desk, wandering

5. Behavioral Features of ADHD Impulsivity Thrill-seeking behavior Risk taking behavior Irritability

6. Developmental Features of ADHD: Children Adolescents Adults Disorganization Impatience Inattentiveness Impulsivity Boredom Irritability Distractible Shift activities Aggressive Low frustration tolerance Motor hyperactivity

7. 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%

8. 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

9. DSM-IV-TR Diagnosis of ADHD in Adults

10. Differential: BAD vs ADHD Symptomatic: episodic vs chronic Decreased need for sleep vs insomnia Hypersexuality Grandiosity Elated mood

12. Co-morbidity OCD Tourette’s Syndrome –a PANDAS phenomenon? Learning Disabilities Conduct Disorder Sleep disturbances: DFA, morning sedation Drug/etOH abuse ODD, CD, ASPD

13. 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

14. 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

15. 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

16. 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, thus precluding absorption.

18. Ritalin ® LA 40 mg Metadate ® CD 60 mg (3 x 20 mg) Concerta ® 54 mg Time (h) 0 51015 0 5 10 15 20 Mean d,l-methylphenidate plasma levels (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.

19. 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.

20. 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

21. Concerta®: a 12 hour MPH preparation

22. 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.

23. Focalin®: dex-methylphenidate The dextro isomer of methylphenidate Dose at ½ the dosage of the racemic mixture

24. Non stimulants with reported efficacy Desipramine Bupropion Modafanil/armodafanil Guanfacine/clonidine Atomoxetine Duloxetine

25. Lisdexamfetamine: Vyvanse® Dextroamphetamine linked to lysine side- chain Activated when lysine cleaved off by enzyme on RBC’s Duration: 12-14 hours

26. Drug Choice Considerations Duration of action Intra-day dosing Compliance is generally poor due to forgetfulness

27. Stimulant Dosing: does not correlate with weight, age, severity of sx. Dose Response

28. 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 5x in their lifetime