ADHD: Current Concepts & Controversies N Nathaniel M. Rickles, - - PowerPoint PPT Presentation

ADHD: Current Concepts & Controversies

N h i l M Ri kl Ph D Ph D BCPP Nathaniel M. Rickles, Pharm.D., Ph.D., BCPP Associate Professor of Pharmacy Practice & Administration Department of Pharmacy Practice Department of Pharmacy Practice Northeastern University School of Pharmacy

Outline

• Introduction/Objectives
• Clinical Presentation
• ADHD- Diagnostic Criteria
• Epidemiology of ADHD
• Costs with ADHD
• ADHD Treatments- Pharmacologic/Non-

Pharmacologic

• ADHD Policy Considerations
• Conclusion

Learning Objectives g j

• Distinguish between childhood and adult

Distinguish between childhood and adult presentations of Attention-Deficit/ Hyperactivity Disorder (ADHD).

• Identify diagnostic tools use childhood and

adult forms of ADHD. D ib h l i d

• Describe pharmacologic and non-

pharmacologic options in the treatment of childhood and adult ADHD.

• Evaluate the role of off-label medications for

the treatment of childhood and adult ADHD.

Learning Objectives (Cont.) g j ( )

• Develop an optimal monitoring plan to
• Develop an optimal monitoring plan to

evaluate efficacy and toxicity of ADHD treatments.

• Analyze the clinical, socioeconomic, and

regulatory challenges and controversies of g y g ADHD treatments for both children and adults.

Clinical Presentation

• MF is a 34 y/o male who reports to his primary
• MF is a 34 y/o male who reports to his primary

care doctor difficulty concentrating at work and sitting still for long (restlessness). His g g ( ) wife complains he is constantly forgetting appointments and often irritable. He is easily bored with activities. He reports having had difficulty concentrating in the classroom when a child and often getting in trouble a child and often getting in trouble.

DSM-IV1

• A. Either 1 or 2 situations:
• A. Either 1 or 2 situations:

– 1. > 6 of the following symptoms of inattention persisting for 6 months or more

• Often fails to give close attention- makes careless mistakes in

g schoolwork, work, or other activities

• Often has difficulty sustaining attention in tasks/play activities
• Often doesn’t follow through on instructions, fails to finish tasks

Oft d t li t t h k di tl

• Often does not listen to when spoken directly
• Often difficulty organizing tasks/activities
• Often avoids to engage in tasks that require sustained mental

effort effort

• Often loses things necessary for tasks/activities
• Easily distracted by extraneous stimuli
• Forgetful in daily activities

DSM-IV1 (Cont.) ( )

– 2. > 6 of the following symptoms of hyperactivity g y p yp y persisting for 6 months or more

• Often fidgets with hands/feet or squirms in seat
• Often leaves seat in situations in which remaining seated

i t d is expected

• Often runs about/climbs excessively in situations that are

inappropriate (feelings of restlessness)

• Often has difficulty playing/engaging in leisure activities

Often has difficulty playing/engaging in leisure activities quietly

• Acts as if driven by a motor
• Talks excessively
• Blurts out answers before questions have been

completed

• Difficulty waiting turn
• Interrupts or intrudes on others
• Interrupts or intrudes on others

DSM-IV1 (Cont.) ( )

• B. Some hyperactive-impulsive or inattentive sxs that
• B. Some hyperactive impulsive or inattentive sxs that

caused impairment were present before 7 yr age

• C. Some impairment from sxs is present in two or

more settings more settings

• D. Must be clear evidence of clinically significant

impairment in social, academic, or occupational f ti i functioning

• E. Not accounted for by any other mental disorders
• Subtypes: Only have A1 (inattentive subtype) or A2

Subtypes: Only have A1 (inattentive subtype) or A2 (hyperactive subtype) or A1 and A2 (combined subtype).

Children vs. Adults

• Hyperactivity, a common symptom in children with

Hyperactivity, a common symptom in children with ADHD, is not as evident in adults.

• Adults may experience restlessness, and fidgeting,

difficulty relaxing and an ever present feeling of being difficulty relaxing, and an ever-present feeling of being nervous or edgy.

• Adults may experience impulsivity as blurting out,

d i i t t i t ti th rude or inappropriate comments or interrupting others during conversation.

• Adults often choose highly active jobs, avoid

g y j situations with little to no activity, work long hours or multiple jobs, easily bored or inpatient, hot tempered, make impulsive decisions. p

Children vs. Adults

• Adults are often forgetting deadlines important

Adults are often forgetting deadlines, important appointments, deadlines, social obligations, procrastination; indecisive, poor time management, diffi lt i iti ti d l ti t k t tl difficulty initiating and completing tasks, constantly shifting attention.

Epidemiology of ADHD p gy

• 7-8% of school-age children2 and 4-5% of

7 8% of school age children and 4 5% of adults3

• Prevalence varies with risk factors including

age male gender chronic health problems age, male gender, chronic health problems, family dysfunction, low socioeconomic status, presence of a developmental impairment and b li i

4

urban living.4

• ADHD more common in boys
• Genetics- Twin studies greater concordance

Genetics Twin studies, greater concordance in monozygotic vs. dizygotic twins. Siblings of hyperactive children 2x likely to have ADHD than general pop; 1 in 2 born to parents with than general pop; 1 in 2 born to parents with ADHD will develop it in their childhood.

Epidemiology of ADHD (Cont.) p gy ( )

• 50 75% will be diagnosed with ADHD
• 50-75% will be diagnosed with ADHD

combined type, 20-30% will be diagnosed with inattentive type, 15% with hyperactive- yp , yp impulsive type.

• Child and adult ADHD commonly co-occurs

y with multiple psychiatric disorders including mood, anxiety, disruptive behavioral di d d b t di d

5 6

disorders, and substance-use disorders.5,6

• About 20-25% of those with ADHD do not

h biditi

7

have comorbidities.7

Costs of ADHD

• Multiple studies showing that ADHD costs 2 3
• Multiple studies showing that ADHD costs 2-3

times more than those without ADHD.8

• ADHD children had higher mean costs than

ADHD children had higher mean costs than those with asthma and those with neither

• disorder. Costs associated with greater use of

g ER, inpatient, and outpatient services.

Pathophysiology p y gy

• Dysfunction of NE DA
• Dysfunction of NE, DA.
• Multi-factorial- genetic, neurochemical,

neurophysiological and psychosocial issues neurophysiological, and psychosocial issues.

• Neuroimaging studies have found lower

cerebral blood flow and metabolic rates in the cerebral blood flow and metabolic rates in the frontal lobe of children with ADHD.

Clinical Course

• ADHD is chronic- begins early in life and

ADHD is chronic begins early in life and continues into adulthood, symptoms change

• ver time
• Early childhood- sxs of hyperactivity

dominate, temper tantrums, rough play, aggression aggression

• Beginning with school, sxs of inattention are

more apparent, and impulsive behaviors and pp , p problems following rules. Poor social interaction and self-esteem may develop.

Clinical Course (Cont.) ( )

• Adolescence motor hyperactivity begins to
• Adolescence- motor hyperactivity begins to

decrease but patients may complain of inner

• restlessness. Disorganization continues,

g , arguing with authority & engage in risky behaviors

Rating Scales: Children & Ad l t 9 Adolescents9

• ADHD Rating Scale IV: 18 items on a 4-point scale

ADHD Rating Scale IV: 18 items on a 4 point scale, ages 5-17, Assesses ADHD sxs based on DSM-IV

• criteria. Recommended as a quick screening tool, not

di ti t l A il bl i diff t i f a diagnostic tool. Available in different versions for parents, teachers, or adolescent self-report.

• Connors Parents and Teaching Rating Scale (CPRS

Connors Parents and Teaching Rating Scale (CPRS and CTRS): 27/28 items on a 4-point scale, ages 3- 17, Assesses ADHD sxs, emotional lability, and

• ppositional behaviors Used in majority of clinical
• ppositional behaviors. Used in majority of clinical

trials as a main outcome measure.

Rating Scales: Children & Ad l t (C t)9 Adolescents (Cont)9

• Inattention-Overactivity with Aggression (IOWA)

Inattention Overactivity with Aggression (IOWA) Conners Teachers Rating Scale:10 items derived from original CTRS, ages 5-11, 4-point scale. 4 l t f clusters of sxs.

• SKAMP Scale: 10 items, 7-point scale; Assesses

ADHD and Oppositional Defiant Disorder (ODD) ADHD and Oppositional Defiant Disorder (ODD) behaviors in the classroom setting.

• SNAP-IV: 90 items, ages 5-17, 4 point scale.

A ADHD ODD b h i d th Assesses ADHD sxs, ODD behaviors, and other

• psychopathology. Used frequently in clinical trials.

Rating Scales: Adults9 g

• Brown ADD Scale:40 items 5 clusters-

Brown ADD Scale:40 items, 5 clusters frequency scale (4-point)

• Conners’ Adult ADHD Rating Scale: Self-

g report and Observer Ratings- long, short, and screening versions W d R i h Ad lt ADHD S l

• Wender-Reimherr Adult ADHD Scale:

measures the severity of target symptoms & assessing current symptoms; 7 categories, 5- g y p ; g , point

• Adult Self-Report Scale:18 item self-screening

ti i lid t d d t k 5 i t questionnaire; validated and takes 5 minutes.

Treatments- Stimulants

• Methylphenidate Dextroamphetamine
• Methylphenidate, Dextroamphetamine,

Mixed-salts Amphetamine

1st li t t t i h i – 1st line treatment since show superior efficacy over non-stimulants9 -11 Various delivery mechanisms exist liquid – Various delivery mechanisms exist- liquid, sprinkle, tablet, capsule, or patch; active and less active isomers, or pro-drug; and less active isomers, or pro drug; immediate, intermediate-release, and extended-release formulations

Methylphenidate y p

Methylphenidate Initial Max / Duration SEs Dose Dose/day (hrs) Immediate Release/ Short A ti (Rit li 5-18 mg, BID/TID 60 mg 3-6 Appetite suppression, d l f l Acting (Ritalin, Methylin, Desoxyn) delay of sleep

• nset, anxiety

Abdominal pain, HA rebound Intermediate-acting (M t d t ER 20 mg QD

• r BID

60 mg 3 - 8 HA, rebound irritability, tics, jitteriness (Metadate ER, Metadate CD, Methylin ER, Ritalin LA, Ritalin SR)

• r BID

, ) Extended release/ long-acting (Concerta, 27 mg QD 10 mg patch 54 mg 30 mg patch 12 Daytrana Patch) p

Dexmethylphenidate y p

Dexmethylphenidate Initial Max / Duration SEs Dose Dose/day (hrs) Short-acting (Focalin) 2.5 mg BID 20 mg 5 Appetite suppression, d l f l delay of sleep

• nset, anxiety

Abdominal pain, HA rebound Extended- release/long-acting (Focalin XR) 5 mg QD 12 HA, rebound irritability, tics, jitteriness

Pharmacokinetic Considerations (C t ) (Cont.)

• MPH- OROS uses an osmotic-release

MPH OROS uses an osmotic release delivery system to simulate TID dosing. First peak in 2 hrs, second peak in next 3-4 hrs, followed by a gradual decline followed by a gradual decline.

• Transdermal has slower onset of action with
• nset often not seen for 3 hrs. Peak at 8 hrs

ft l t P t h d ft 9 h after placement. Patch removed after 9 hrs.

• Dex-MPH IR faster to peak (1-1.5 hrs) than
• MPH. Dex-MPH-XR delivers 50% doses

immediately with peak in 1.5 hrs, second peak in 6.5 hrs.

Pharmacokinetic Considerations (C t ) (Cont.)

• IR products reach peak plasma in 1-3 hrs,

IR products reach peak plasma in 1 3 hrs, clinical effects in 30 - 60 min; often given am and noon (later dose can help with homework)

• SR products reach peak plasma in 4 5 hrs
• SR products reach peak plasma in 4 -5 hrs
• LA uses an extended-release beaded

technology to simulate twice a day dosing; gy y g 50% of dose like IR, 50% second peak occurs 5-6 hrs after ingestion.

• CD uses same technology as LA but 30%

CD uses same technology as LA but 30% release initially, 70% released later with second peak 5-6 hrs after ingestion.

Amphetamines p

Amphetamines Initial Dose Max Dose/day Duration (hrs) SEs Dose Dose/day (hrs) Dextroamphetamine (Dexedrine,Dextrostat) (D d i S l ) 2.5 mg QD- BID: 3-5 y/o 5 mg BID: >6 40 mg 40 4 – 5 8 Appetite suppression, delay of sleep (Dexedrine Spansules) Dextroamphetamine Liquid (Liquadd) 5 mg BID: >6 y/o 2.5 mg BID- TID 40 mg 40 mg 8 4 -5 delay of sleep

• nset, anxiety

Abdominal pain, HA, Liquid (Liquadd) rebound irritability, tics, jitteriness Mixed Amphetamine Salts (Adderall) 2.5 mg QD- BID: 3-5 y/o 5 mg BID: >6 40 mg 4-6 Mixed Amphetamine Salts XR (Adderall XR) 5 mg BID: >6 y/o 10 mg QD 30 mg 10-12 hrs Salts XR (Adderall XR) hrs

Amphetamines (Cont.) p ( )

Amphetamines Initial Dose Max Dose/day Duration (hrs) SEs Dose Dose/day (hrs) Lisdexamfetamine (Vyvanse) 30 mg QD: 6- 12 y/o 50 mg QD: 70 mg 12 Appetite suppression, delay of sleep 50 mg QD: >13 delay of sleep

• nset, anxiety

Abdominal pain, HA, rebound irritability, tics, jitteriness

Pharmacokinetic Considerations

• Younger children eliminate amphetamines

Younger children eliminate amphetamines faster than adolescents and adults

• Dextroamphetamine IR reaches peak in 2 hrs

while extended release achieves peak in 8 while extended-release achieves peak in 8

• hrs. Clinical effects seen within 30-60 min.
• Mixed amphetamine salts IR reach peak in

p p about 3 hrs, XR uses beaded technology with 2 peaks.

• Lisdexamfetamine- prodrug converted to

Lisdexamfetamine prodrug converted to dextroamphetamine and L-lysine in gut.

• High fat meal may delay time to peak by 2

hrs.

Monitoring/Counseling Notes g g

• Monitor weight and blood pressure

Monitor weight and blood pressure periodically

• Stimulants taken in am unless instructed
• therwise

Last dose not too late in the day to

• therwise. Last dose not too late in the day to

reduce insomnia.

• All extended-release products should not be

p crushed or chewed

• MPH-LA, MPH-CD, Dex-MPH-XR, and mixed

amphetamine salts XR can be opened up and amphetamine salts XR can be opened up and sprinkled on applesauce for immediate consumption and not heated.

Monitoring/Counseling Notes (C t ) (Cont.)

• Lisdexamfetamine can be opened & dissolved

in a glass of water for immediate use in a glass of water for immediate use.

• MPH and dextroamphetamine are available

as liquids. as liquids.

• Apply MPH transdermal patch 2 hrs before

needed effect.

• Stimulant effects of medications can be

additive with other stimulants. MAOI h ld t b i ith 14 d f

• MAOIs should not be given with 14 day of

stimulant therapy.

• TCA concentrations may increase when taken
• TCA concentrations may increase when taken

with MPH

Atomoxetine

• Atomoxetine is first-line for non-
• Atomoxetine is first-line for non-

stimulant options and FDA approved for ADHD. ADHD.

• Inhibits reuptake of NE in CNS
• Dosing:
• Dosing:

– <70 kg: 0.5 mg/kg/day, after 3 days increase to target 1.2 mg/kg/day; Max g g g y; dose: 1.8 mg/kg/day – > 70 kg: 40 mg daily, increase to 80 mg ft 3 d M d 100 d il after 3 days. Max dose: 100 mg daily.

Atomoxetine- Counseling N t Notes

• Commonly reported side effects:
• Commonly reported side effects:

– GI discomfort, minimized with food – Insomnia & Dizziness: Dosing twice daily – Insomnia & Dizziness: Dosing twice daily may lower side effects – Monitor for signs of heptatoxicity g p y

• Since metabolized through CYP 450

2D6 and 2C19 to active metabolites, dosage adjustments should be made when given with a 2D6 inhibitor

Atomoxetine- Monitoring/ C li N t (C t ) Counseling Notes (Cont.)

• Atomoxetine can take 4 weeks to work
• Atomoxetine can take 4 weeks to work.
• May have particular use in populations

f hi h ti l t bl ti (ti for which stimulants are problematic (tic disorders, anxiety disorders).

• Carries a black box warning against

suicidality in pediatric populations.

Clonidine/Guanfacine

• Alpha 2 adrenergic agonists which block
• Alpha-2 adrenergic agonists which block

inhibitory pre-synaptic receptors regulating NE.

• Clinical trials have shown efficacy in treating
• ADHD. May be more effective in treating

y g hyperactive sxs than inattention.

• Guanfacine extended-release- FDA approved

for ADHD. Start 0.05 to 0.08 mg/kg once daily for monotherapy. Can titrate weekly to 0.12 /k / d (M 4 /d ) mg/kg/ day (Max 4 mg/day).

Clonidine/Guanfacine

• Clonidine: Start at 0 05 mg/day Increase by
• Clonidine: Start at 0.05 mg/day. Increase by

0.05 mg/day q 3 – 7 days to a dose of 0.003 – 0.005 mg/kg/day given TID/QID. Maximum g g y g Q dose is 0.4 mg/day.

• Common side effects: sedation, hypotension,

yp dizziness.

• Drug Interactions: CNS depressants and

drugs that lower heart rate, Mirtazepine, Yohimbine

Other Pharmacologic Options g p

• Bupropion in a small # of clinical trials it has
• Bupropion- in a small # of clinical trials, it has

been shown to be effective in ADHD.12,13

– Dosing: SR, 100 mg QD x 3 days, 150 mg daily, Dosing: SR, 100 mg QD x 3 days, 150 mg daily, 150 mg BID; ER. 150 mg QD, 300 mg QD. – Takes 4-6 wks to work – Irritability, agitation, diarrhea, worsen tics – 2nd line of therapy, useful in patients with comorbid depression or nicotine dependence depression or nicotine dependence.

Other Pharmacologic Options (C t ) (Cont.)

• Modafinil
• Modafinil
• Some trials showing efficacy but safety

(i d i k f St concerns (increased risk of Steven- Johnson syndrome)14

– Dosing: 100 mg daily and titrate to 300 mg daily Sid Eff t d d tit i i – Side Effects: decreased appetite, insomnia headaches, exacerbate mania Thi d li ti if f il t th t – Third-line option if failure to other agents

Other Pharmacologic Options (C t ) (Cont.)

• Tricyclic Antidepressants Imipramine
• Tricyclic Antidepressants- Imipramine,

Nortripytline, and Desipramine-

Sid Eff t – Side Effects – Some treatment success; considered 3rd line for ADHD option for patients with line for ADHD- option for patients with comorbid depression, anxiety, or contraindication to other agents contraindication to other agents

Non-Pharmacologic Options g p

• Family-based Interventions

Family based Interventions

• School-Focused Interventions

– Placing child in front of classroom, small classroom g , sizes, well-organized class schedule

• Child-Focused Interventions

C l t & Alt ti M di i

• Complementary & Alternative Medicines-

– Mixed evidence; no clear picture. Some positive results with minerals zinc, iron, antioxidant results with minerals zinc, iron, antioxidant botanical French maritime pine bark. – Lack of much support for Omega-3, Ginkgo Biloba, and Hypercium perforatum (St John’s wort) and Hypercium perforatum (St. John s wort)

Treatment Summary15 y

• Predominant ADHD
• Predominant ADHD
• Step 1: MPHD or DEX/MXA
• Step 2: If inadequate response, switch

to drug class not used in step 1

• Step 3: If inadequate response, try

Bupropion, TCA, or Atomoxetine p p , ,

Treatment Summary15 y

• Predominant Comorbidity Tic Disorder
• Predominant Comorbidity- Tic Disorder
• Step 1: Consider Bupropion, clonidine,

f i guafacine

• Step 2: Partial response- add stimulant.

If inadequate response, choose alternative to Step 1 choice

Treatment Summary15 y

• Predominant Comorbidity Bipolar or
• Predominant Comorbidity- Bipolar or

Severe Aggression St 1 lithi ti l t

• Step 1: lithium, anticonvulsant, or

atypical antipsychotic

• Step 2: Partial response- add bupropion
• r stimulant. If inadequate response,

choose alternative to Step 1 choice

Treatment Summary15 y

• Predominant Comorbidity Anxiety/
• Predominant Comorbidity- Anxiety/

Depression St 1 A tid t

• Step 1: Antidepressant
• Step 2: Partial response- add stimulant.

If inadequate response, choose alternative to Step 1 choice

Policy Thoughts/Discussion y g

• No guidelines for adult ADHD

No guidelines for adult ADHD

• Medical management (primarily stimulants) and

combo of medication and behavioral treatment yielded significantly greater improvement in ADHD yielded significantly greater improvement in ADHD sxs than behavioral alone or routine community care. Combo group had an advantage over the medical management group 16 management group.16

• High rates of medication non-adherence.17
• Only 36% of adults with ADHD reported taking a

y g prescription medication for the disorder.18

Policy Thoughts/Discussion (C t ) (Cont.)

• Among those 18-49 whose private insurance paid costs

for ADHD medications in the past 30 days 16 6% for ADHD medications in the past 30 days, 16.6% diverted these medications. Men were more likely than women to engage in such diversion.19 E ti t d l f di t d i ti i 30 d

• Estimated value of diverted prescriptions in a 30-day

period is $8 million ($83 to 204 million annually).19

• Diversion accounted for 3.6% of the total costs that

private insurers paid for ADHD medications.19

• Require PAs for stimulant use?
• Require PAs on FDA approved medication guanfacine
• Require PAs on FDA-approved medication, guanfacine-

extended release, but no formulary restriction on guanfacine or clonidine that are not FDA approved

References

1.

• 1. American Psychiatric Association. DSM

American Psychiatric Association. DSM-

• IV

IV-

• TR.

TR. y Washington, DC: American Psychiatric Washington, DC: American Psychiatric Association;2000. Association;2000. 2.

• 2. Barbaresi WJ, Katusic SK, Colligan RC, et al. How

Barbaresi WJ, Katusic SK, Colligan RC, et al. How , , g , , , g , common is attention common is attention-

• deficit/ hyperactivity disorder?

deficit/ hyperactivity disorder? Incidence in a population Incidence in a population-

• based birth cohort in

based birth cohort in Rochester, Minn. Rochester, Minn. Arch Pediatric Adolesc Med Arch Pediatric Adolesc Med 2002;156(3):217 2002;156(3):217 224 224 2002;156(3):217 2002;156(3):217-224. 224. 3.

• 3. Kessler RC, Adler L, Barkley R, et al. The prevalence

Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: and correlates of adult ADHD in the United States: results from the National Comorbidity Survey results from the National Comorbidity Survey results from the National Comorbidity Survey results from the National Comorbidity Survey Replication.

• Replication. American Journal of Psychiatry

American Journal of Psychiatry 2006;163(4):716 2006;163(4):716-

• 723.

723.

References

4 Lavigne JV Gibbons RD Christoffel KK et al Lavigne JV Gibbons RD Christoffel KK et al 4. 4. Lavigne JV, Gibbons RD, Christoffel KK, et al. Lavigne JV, Gibbons RD, Christoffel KK, et al. Prevalence rates and correlates of psychiatric Prevalence rates and correlates of psychiatric disorders among preschool children. disorders among preschool children. J Am Acad J Am Acad Child Ad l P hi t Child Ad l P hi t 1996 35(2) 204 1996 35(2) 204 214 214 Child Adolesc Psychiatry Child Adolesc Psychiatry 1996;35(2):204 1996;35(2):204-214. 214. 5. 5. Angold A, Costello EJ, Erkanli A. Comorbidity. J Angold A, Costello EJ, Erkanli A. Comorbidity. J Child Psychol Psychiatry 1999;40(1):57 Child Psychol Psychiatry 1999;40(1):57-87. 87. Child Psychol Psychiatry 1999;40(1):57 Child Psychol Psychiatry 1999;40(1):57 87. 87. 6. 6. Murphy K, Barkley RA. Attention deficit hyperactivity Murphy K, Barkley RA. Attention deficit hyperactivity disorder adults: comorbidities and adaptive disorder adults: comorbidities and adaptive i i t C P hi t 1996 37(6) 393 i i t C P hi t 1996 37(6) 393

• impairments. Compr Psychiatry 1996;37(6):393
• impairments. Compr Psychiatry 1996;37(6):393-

401. 401.

References

7. 7. Lahey BB, Appelgate B, McBurnett K, et al. DSM Lahey BB, Appelgate B, McBurnett K, et al. DSM-IV IV 7. 7. Lahey BB, Appelgate B, McBurnett K, et al. DSM Lahey BB, Appelgate B, McBurnett K, et al. DSM IV IV field trials for attention deficit hyperactivity disorder field trials for attention deficit hyperactivity disorder in children and adolescents. in children and adolescents. Am J Psychiatry Am J Psychiatry 1994;151(11):1673 1994;151(11):1673-1685 1685 1994;151(11):1673 1994;151(11):1673 1685. 1685. 8. 8. Faraone SV. Using meta Faraone SV. Using meta-

• analysis to compare the

analysis to compare the efficacy of medications for Attention efficacy of medications for Attention-

• Deficit/

Deficit/ Hyperactivity Disorder in youths P &T 2009; Hyperactivity Disorder in youths P &T 2009; Hyperactivity Disorder in youths. P &T 2009; Hyperactivity Disorder in youths. P &T 2009; 34(12):678 34(12):678-

• 694.

694. 9. 9. Minkoff NB. ADHD in managed care: An Minkoff NB. ADHD in managed care: An t f th b d f ill d d t f th b d f ill d d assessment of the burden of illness and proposed assessment of the burden of illness and proposed initiatives to improve outcomes. Am J Manage Care initiatives to improve outcomes. Am J Manage Care 2009;15;S151 2009;15;S151-

• S159.

S159.

References

10 10 American Academy of Child and Adolescent

American Academy of Child and Adolescent

10.

• 10. American Academy of Child and Adolescent

American Academy of Child and Adolescent

• Psychiatry. Practice parameter for the assessment
• Psychiatry. Practice parameter for the assessment
• f children and adolescents with attention
• f children and adolescents with attention-
• deficit/hyperactivity disorder. J Am Acad Child

deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007; 46(7):894 Adolesc Psychiatry 2007; 46(7):894-

• 921.

921. 11 11 Pliszka SR Crismon ML Hughes CW et al The Pliszka SR Crismon ML Hughes CW et al The 11.

• 11. Pliszka SR, Crismon ML, Hughes CW, et al. The

Pliszka SR, Crismon ML, Hughes CW, et al. The Texas children’s medication algorithm for Texas children’s medication algorithm for pharmacotherapy of Attention pharmacotherapy of Attention-

• Deficit/Hyperactivity

Deficit/Hyperactivity Di d J A A d Child Ad l P hi t Di d J A A d Child Ad l P hi t

• Disorder. J Am Acad Child Adolesc Psychiatry
• Disorder. J Am Acad Child Adolesc Psychiatry

2006;45(6):642 2006;45(6):642-

• 57.

57.

References

12. 12. Barrickman L, Perry P, Allen AJ et al.Bupropion Barrickman L, Perry P, Allen AJ et al.Bupropion 12. 12. Barrickman L, Perry P, Allen AJ et al.Bupropion Barrickman L, Perry P, Allen AJ et al.Bupropion versus methylphenidate in attention versus methylphenidate in attention-

• deficit/hyperactivity disorder. J Am Acad Child

deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1995;34(5):649 Adolesc Psychiatry 1995;34(5):649-57 57 Adolesc Psychiatry 1995;34(5):649 Adolesc Psychiatry 1995;34(5):649 57. 57. 13. 13. Daviss WB, Bentivoglio P, Racusin R, et al. Daviss WB, Bentivoglio P, Racusin R, et al. Bupropion sustained release in adolescents with Bupropion sustained release in adolescents with comorbid attention comorbid attention deficit/ hyperactivity disorder deficit/ hyperactivity disorder comorbid attention comorbid attention-deficit/ hyperactivity disorder deficit/ hyperactivity disorder and depression. J am Acad Child Adolesc and depression. J am Acad Child Adolesc Psychiatry 2001;40(3):307 Psychiatry 2001;40(3):307-

• 14.

14.

14 14 Biederman J Swanson JM Wigal SB et al Efficacy Biederman J Swanson JM Wigal SB et al Efficacy 14.

• 14. Biederman J, Swanson JM, Wigal SB, et al. Efficacy

Biederman J, Swanson JM, Wigal SB, et al. Efficacy and safety of modafinil film and safety of modafinil film-

• coated tablets in

coated tablets in children and adolescents with attention children and adolescents with attention-

• d fi it/h

ti it di d lt f d fi it/h ti it di d lt f deficit/hyperactivity disorder: results of a deficit/hyperactivity disorder: results of a randomized,double randomized,double-

• blind, plabebo

blind, plabebo-

• controlled,

controlled, flexible dose study. Pediatrics 2005;116(6):777 flexible dose study. Pediatrics 2005;116(6):777-

• 84.

84. 15.

• 15. Dopheide JA, Theesen KA, Malkin M. Psychiatric

Dopheide JA, Theesen KA, Malkin M. Psychiatric disorders of childhood treatments. In DiPiro JT, et disorders of childhood treatments. In DiPiro JT, et al eds Pharmacotherapy: A Pathophysiology al eds Pharmacotherapy: A Pathophysiology al., eds. Pharmacotherapy: A Pathophysiology al., eds. Pharmacotherapy: A Pathophysiology

• Approach. 6
• Approach. 6th

th ed. New York, NY: McGraw

• ed. New York, NY: McGraw-
• Hill;2005:1145

Hill;2005:1145-

• 1154.

1154.

References

16 16 The MTA Cooperative Group A 14 The MTA Cooperative Group A 14-month month 16.

• 16. The MTA Cooperative Group. A 14

The MTA Cooperative Group. A 14 month month randomized clinical trial of treatment strategies for randomized clinical trial of treatment strategies for attention attention-

• deficit/hyperactivity disorder. Arch Gen

deficit/hyperactivity disorder. Arch Gen P hi t 1999 56 1073 P hi t 1999 56 1073 86 86 Psychiatry 1999;56: 1073 Psychiatry 1999;56: 1073-86. 86. 17.

• 17. Pappadopulos E, Jensen PJ, Chait AR, et al.

Pappadopulos E, Jensen PJ, Chait AR, et al. Medication adheren in the MTA: saliva Medication adheren in the MTA: saliva Medication adheren in the MTA: saliva Medication adheren in the MTA: saliva methylphenidate samples versus parent report and methylphenidate samples versus parent report and mediating effect of concomitant behavioral mediating effect of concomitant behavioral treatment J Am Acad Child Adolesc Psychiatry treatment J Am Acad Child Adolesc Psychiatry

• treatment. J Am Acad Child Adolesc Psychiatry
• treatment. J Am Acad Child Adolesc Psychiatry

2009;Mar 19. 2009;Mar 19.

References

18 18 Biederman J Breaking news: the social and Biederman J Breaking news: the social and 18.

• 18. Biederman J. Breaking news: the social and

Biederman J. Breaking news: the social and economic impact of ADHD. Discussion presented economic impact of ADHD. Discussion presented at: Attention Deficit Hyperactivity Disorder (ADHD) at: Attention Deficit Hyperactivity Disorder (ADHD) AMA M di B i fi S t b 9 2004 N Y k AMA M di B i fi S t b 9 2004 N Y k AMA Media Briefing; September 9, 2004; New York, AMA Media Briefing; September 9, 2004; New York, NY. NY. 19.

• 19. Aldridge AP, Kroutil LA, Cowell AJ, et al. Medication

Aldridge AP, Kroutil LA, Cowell AJ, et al. Medication 19.

• 19. Aldridge AP, Kroutil LA, Cowell AJ, et al. Medication

Aldridge AP, Kroutil LA, Cowell AJ, et al. Medication costs to private insurers of diversion of medications costs to private insurers of diversion of medications for attention for attention-

• deficit hyperactivity disorder.

deficit hyperactivity disorder. Pharmacoeconomics 2011;29(7):621 Pharmacoeconomics 2011;29(7):621 635 635 Pharmacoeconomics 2011;29(7):621 Pharmacoeconomics 2011;29(7):621-635. 635.