ADHD: Childneurosciencecme.com/library/MM019-day2-1400-mattox...for ADHD Wellbutrin XL 150 150-300 1 Seizures, bulimia, anorexia nervosa, abrupt discontinuation of alcohol or benzodiazepines,

ADHD: ChildGail A. Mattox, MD,FAACAPMorehouse Schoolof Medicine

Russell E. Scheffer, MDUniversity of KansasSchool of Medicine-Wichita

LearningObjectiveImplement assessmenttools for accuratediagnosis and developan evidence-basedtreatment strategy tooptimize themanagement of ADHDin children andadolescents

RecognizingADHD in Childrenand AdolescentsGail A. Mattox, MD,FAACAPMorehouse Schoolof Medicine

Gail A. Mattox, MD, FAACAPDisclosures

Research/Grants: None

Speakers Bureau: None

Consultant: None

Stockholder: None

Other Financial Interest: None

Advisory Board: None

LearningObjectiveRecognize the importanceof early identification ofsymptoms for improveddiagnosis and treatment ofchildren and adolescentswith ADHD

ADHDA Common Disorder

ADHD

One of the most common psychiatricdisorders of childhood

A neurobiological disorder Results in significant impairment Most will continue to meet criteria during

adolescence Frequently associated with comorbid

disorders

http://www.cdc.gov/ncbddd/adhd/data.html. Accessed July 8, 2009.

Prevalence and Impact

Common disorder, long-lasting 5–10% of children in United States 2.5x more frequently reported in males Disparities in access and treatment Cost of illness $36–52 billion More likely to have major injuries Greater risk for accidents


Core Symptoms

Inattention

Impulsivity

Hyperactivity

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,(DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000.

ADHD Types

ADHD Combined Type

ADHD Predominantly Inattentive Type

ADHD PredominantlyHyperactive/Impulsive Type


ADHD Core Symptoms

Difficulty sustaining attention Does not seem to listen Makes careless mistakes Difficulty organizing tasks Easily distracted Often forgetful Often loses things Often does not follow through

Difficulty playing quietly Fidgets, squirms Leaves seat Runs about Often “on the go” Often talks excessively Blurts out Often interrupts Can’t wait turn

Greenhill L. J Clin Psychiatry 1998;5(suppl 7):31-41.

ADHD Presentation DuringAdolescence

Risky, impulsive behavior– Driving, drugs/alcohol, sex, risk-taking

Gives up easily Difficulty organizing tasks, poor time management, and

easily distracted– Email, IM/texting, jobs, sports

Interrupts Fooling around behavior Annoys others Often in trouble, difficulty with authority

ADHD Diagnostic CriteriaDSM-IV-TR

Usually appears earlybetween 3–6 musthave impairmentbefore age 7

Impairment in two ormore settings

Clinically significantimpairment x 6 mos

Must exclude otherdisorders

6 or more symptoms ofinattention or

6 or more symptoms ofhyperactivity orimpulsivity



State-Based Prevalence ofADHD Diagnosis

Correlates of ADHD

Low self-esteem

Impaired peer relationships

Lower academic achievement

School failure

Family difficulties

Parent InterviewADHD symptoms

ImpairmentComorbidity

Academic functionFamily historyMedical and

developmental history

Behavior RatingScalesParent

Teacher

Child InterviewADHD symptoms?

InconsistenciesMental status exam

NeuropsychologicalTesting

Academic impairmentLearning disabilitiesExecutive function

optional

Laboratory/Neurological TestingOnly if strong evidence in

medical history

Pliszka S, et al. J Am Acad Child Adolesc Psychiatry 2007;46:894-921.

ADHD Assessment

AACAP Practice GuidelinesRecommendations

Unremarkable medical history laboratoryand neurological testing is not indicated

Psychological and neuropsychological arenot mandatory

Neuroimaging a research tool

Pliszka S, et al. J Am Acad Child Adolesc Psychiatry 2007;46:894-921.

Behavior Rating Scales forADHD Recommended

AcademicPerformance RatingScale

ADHD Rating ScaleIV

Child BehaviorChecklist

Conners ParentRating Scale

Conners TeacherRating Scale

Conners WellsAdolescent SelfReport Scale

Vanderbilt ADHDDiagnostic Parentand Teacher Scales

Resources for Rating Scales

National Resource Center on ADHDwww.help4adhd.org

American Academy of Pediatricswww.aap.org

American Academy of Child and Adolescent Psychiatrywww.aacap.org

Bright Futureswww.brightfutures.orgwww.brightfutures.org/mentalhealth/pdf/professionals/bridges/adhd.pdf

www.adhd.net

ADHD and Comorbidity

Look for comorbidities in patients withADHD

Offer appropriate treatment options for bothADHD and comorbidities

MTA Cooperative Group. Arch Gen Psychiatry 1999;56:1073-1086.

Affective DisorderAnxietyDisorders

Disruptive BehaviorDisordersODD, CD

Mania/Hypomania

ADHD33.5%

2.2%ODD, 39.9%

CD, 14.3%

22%

Common ComorbiditiesPrevalence with ADHD

Summary

ADHD is a common childhood disorder withnegative impact on multiple areas offunction

High prevalence of continuation of disorderinto adolescence with varying presentations

Assessment and diagnosis requires multi-pronged approach

Psychiatric comorbidities prevalent

Intervention StrategiesAre Effective

TreatmentStrategies forChildhood ADHDRussell E. Scheffer, MDUniversity of KansasSchool of Medicine-Wichita

Russell E. Scheffer, MDDisclosures

Research/Grants: Wyeth Pharmaceuticals

Speakers Bureau: None

Consultant: AstraZeneca Pharmaceuticals LP

Stockholder: None

Other Financial Interest: None

Advisory Board: None

LearningObjectiveCompare and contrastthe current treatmentoptions for ADHD anddevelop individualizedmanagementstrategies for eachpatient

Treatment Overview

Why Treat It? Myths and Legends Mechanisms of Action Drug Delivery System Treatment Choices Optimizing Treatment—Sculpting Side Effects Concurrent Conditions

ADHD: Impact of Untreated &Under-Treated ADHD

Patient

Society Substance use disorders:

2x risk8

Earlier onset8

Less likely to quit smokingin adulthood9

Health Care System50% ↑ in bike accidents1

33% ↑ in ER visits2

2-4x moremotor vehicle crashes3-5

School & Occupation

46% expelled6

35% drop out6Lower occupational

status7

Employer↑ parental

absenteeism13

and ↓ productivity13

Family3-5x ↑ parental divorce

or separation10,11 2-4x ↑ sibling fights12

See supplemental bibliography for a complete list of references.

Concerns About Drug Abuse

Stimulants are Schedule II and should be takenseriously and monitored closely

You do not get sued less because you did not see thepatient

Addictive potential is based upon rapid onset(absorption) and euphoric effects

Diversion—mostly for amateurs and college students Tactics to change schedule

– Prodrug– Getting rid of the L isomer (early peak onset)

Odds Ratio = 6.3; p < .001Biederman J, et al. Pediatrics 1999;104:e20.

Substance Abuse in ADHDYouth Growing UpOverall Rate of Substance Abuse

(n = 19) (n = 56) (n = 137)

Presynaptic vesicle+ release

NE Reuptake

DA Reuptake

Synaptic Actions of ADHDMedications

Blocks reuptake of DA Blocks reuptake ofDA and NE

Increases recirculatingpools

Blocks NE reuptake Some DA reuptake

MethylphenidateD-AmphetamineAtomoxetine

Drug Delivery SystemsIt’s Really What Differentiates the Meds

Immediate-release

Sustained-release– Beads (bid dosing in one capsule)– OROS (ascending profile—sipping studies)

Methylphenidate transdermal patches

Prodrug lisdexamfetamine dimesylateeffective 13 hours post-dose

-1

0

1

2

3

Effe

ct S

ize

Non-Stimulant Immediate-ReleaseStimulants

Long-ActingStimulants

Represents the meaneffect size for each classof medication

p < .05 for stimulants vs. non-stimulantsFaraone SV, et al. Medscape General Medicine 2006;8:4. Available at:www.medscape.com/viewarticle/543952.

Effect Sizes for FDA-ApprovedADHD Medications

Recommended Medicationsfor ADHD

110-30Daytrana2-32.5-102.5-5Focalin‡

120-4020Ritalin LA

110-2010Metadate ER, MetadateCD, Methylin ER

127-5418-27ConcertaMarked anxiety,tension, agitation,glaucoma, use ofmonoamine oxidaseinhibitors, seizures,tics

Appetite suppression,stomachaches,headaches, irritability,weight loss, decelerationin rate of growth,exacerbation of psychosis,exacerbation of tics, mildincrease in blood pressureand pulse

2-310-205-10Ritalin, MethylinMethylphenidate†

mg

ContraindicationsSide EffectsDosesper Day

UsualDose

InitialDoseMedication*

* For each category the generic drug is given and dosing information for each named marketed drug.† The manufacturer states that seizures and tic disorder are contraindications; research supports the use

of stimulants in children with seizures that have stabilized with the use of anticonvulsants and in childrenwith tic disorder or Tourette’s disorder. With use of long-acting methylphenidate or dextroamphetamineproduct, a short-acting product may be added at 4 p.m. to 6 p.m. for homework or special activities;appetite and sleep onset are then carefully monitored.

‡ Focalin is a dextro isomer of methylphenidate that is given at a lower level.


110-305-10Addreall XR

1-25-305-10Adderall

1-25-155-10Dexedrine Spansule

Cardiovasculardisease,hypertension,hyperthyroidism,glaucoma, drugdependence, use ofmonoamine oxidaseinhibitors

Appetite suppression,stomachaches,headaches, irritability,weight loss, possiblegrowth inhibition,exacerbation of psychosis,exacerbation of tics, mildincrease in blood pressureand pulse

2-35-205Dexedrine

Dextroamphetamine (sulfate alone and in combination with amphetamine salts)†

mg


UsualDose


* For each category the generic drug is given and dosing information for each namedmarketed drug.

† The manufacturer states that seizures and tic disorder are contraindications; researchsupports the use of stimulants in children with seizures that have stabilized with the use ofanticonvulsants and in children with tic disorder or Tourette’s disorder. With use of long-acting methylphenidate or dextroamphetamine product, a short-acting product may beadded at 4 p.m. to 6 p.m. for homework or special activities; appetite and sleep onset arethen carefully monitored.


Advancedarteriosclerosis,symptomaticcardiovasculardisease, moderate toserve hypertension,hyperthyroidism,knownhypersensitivity oridiosyncratic reactionto sympathomimeticamines, glaucoma,history of drugabuse, use ofmonoamine oxidaseinhibitors

Vomiting, nausea, drymouth, upper abdominalpain, pyrexia, Insomnia,irritability, appetitesuppression, irritability,weight loss, possiblegrowth inhibition,exacerbation of psychosis,dizziness, somnolence,exacerbation of tics, mildincrease in blood pressureand pulse

130-7030Vyvanse

Lisdexamfetamine dimesylate (LDX)mg


UsualDose


• For each category the generic drug is given and dosing information for each namedmarketed drug.

www.fda.gov


1150-300150Wellbutrin XL

Seizures, bulimia, anorexianervosa, abruptdiscontinuation of alcoholor benzodiazepines, use ofmonoamine oxidaseinhibitors or otherbupropion products (e.g.,Zyban)

Weight loss, insomnia,agitation, anxiety, drymouth, seizures, others1-2150100-150Wellbutrin SR

Bupropion∫

Jaundice or other clinical orlaboratory evidence of liverinjury, use of monoamineoxidase inhibitors, narrow-angle glaucoma

Appetite suppression,nausea, vomiting,fatigue, weight loss,deceleration in rate ofgrowth, mild increase inblood pressure and pulse

118-6010-25Strattera

Atomoxetineƒ

mg


UsualDose

InitialDoseMedication

* For each category the generic drug is given and dosing information for each named marketed drug.ƒ Younger children may need two doses a day.∫ Bupropion has not been approved by the FDA for pediatric use. Only sustained release (twice daily) or extended release

(once daily) are recommended for adolescents. There is a higher incidence of side effects with the immediate-releasepreparation.

Percent “Normalized” at 14-MonthEndpoint Across the Four MTA Groups

The classroom controls were drawn from the same classroom cohorts as MTA children wereoriginally, and were age- and gender-matched to assure comparability with MTA subjects. The“normalization” indicator was based on a composite of parent and teacher ratings, with the overallsymptom cutoff required to be indicative of “little or no” symptoms).Swanson JM, et al. J Am Acad Child Adolesc Psychiatry 2001;40:168-179.

88%

68%56%

34%25%

NS

NS

SculptingOptimizing Treatments

Goals: Good coverage throughout the day(or when needed)

Avoid or fill excessive troughs How do you know if this is the best they can be?

Switches can improve or worsen MPH vs. dAMPH Optimal dosing—frequently we stop when they

are better with little idea of what they could be Other treatments

Sculpting Solutions

Problem Solution 1 Solution 2

Lack of early morningefficacy

Add an IR dose to theXR Possibly atomoxetine

Can not get readyin the a.m.

Take meds 1 hourbefore desired wake

up time

Take an IR doseupon awakening

Does not last long enough Add an IR dose later Add a second XR doseor atomoxetine

Trouble settling for bed Clonidine orguanfacine HS dose of IR stimulant

Wakes up late onweekends Consider a patch Use IR instead

Side Effects

GI distress

Vomiting

Nausea

Dry mouth

Irritability

Tics

Insomnia

Affective lability

Decreased appetite(anorexia)

Increased pulse

Increased bloodpressure

Wear Off and Rebound

Stimulants are “out” of the blood streamevery day

Irritability and moodiness can occur as themeds are wearing off

Poor “settling” for bed is frequently acharacteristic of patients with ADHD evenbefore treatment—it becomes a focus wheneverything else is better

Alpha2 adrenergic agonists can improve this

Non-Stimulants

Atomoxetine

Alpha2 adrenergic agonists

Bupropion

Tricyclic antidepressant

ADHD Comorbidity

Conduct disorder

Oppositional defiantdisorder

Tic disorders

Sleep problems:Failure to settle—accelerate atbedtime

Depression

Anxiety disorders

Bipolar disorder

Tourette’s disorder

Learning disorders

Behavioral interventions should be considered at each step for disruptive behavior disorders.

Treatment of ConcurrentConditions

Condition Solution 1 Solution 2

Aggression Alpha2 adrenergic agonist Antipsychotic or moodstabilizer

Anxiety disorder Start low and go slow withstimulant

Treat the anxiety disorder oratomoxetine

Depression Treat ADHD first,if still present SSRI Consider bupropion

Tic disorder Lower dose Alpha2 adrenergic agonist

Bipolar disorder Treat BPD first Consider over stabilization

Learning disorder Treat ADHD Refer to learning specialist

Conduct/ODD Treat ADHD Consider Alpha2 agonist,antipsychotic later

1. Loe IM, Feldman HM. Ambul Pediatr 2007:82-90.2. MTA Cooperative Group. Arch Gen Psychiatry 1999;56:1073-1086.3. Jensen PS, et al. J Am Acad Child Adolesc Psychiatry 2007;46:989-1002.

Why Consider Non-PharmacologicalTreatment for ADHD?

Medication does not ameliorate existing skillsdeficits1

– Deficits in prosocial skills remain– Academic achievement does not improve

Some children only partial responders2

Poor maintenance effects after withdrawal ofmedication3

No appreciable impact on long-term outcome3

1. Conners CK, et al. J Am Acad Child Adolesc Psychiatry 2001;40:159-167.2. MTA Cooperative Group. Arch Gen Psychiatry 1999;56:1073-1086.3. Vitielo B, et al. J Am Acad Child Adolesc Psychiatry 2001;40:188-196.

Why Consider Non-PharmacologicalTreatment for ADHD?

Patient preferences and satisfaction Some individuals unable to tolerate side effects of

medications Added benefits of combining pharmacologic and

psychosocial treatments1,2,3

– May improve broader outcomes– May be necessary for some individuals to achieve

significant improvement– May lower the acute and lifetime dosages of medication

Summary

Individualize treatment strategies for eachpatient based on safety, efficacy, andtolerability of treatment options

Drug delivery systems matter Sculpting is an important option for

optimizing treatment Consider comorbid psychiatric disorders

in management strategy

an educational series offered byCME Outfitters, LLC

This CME/CE activity isco-sponsored by

Recognizing ADHD in Children and Adolescents Gail A. Mattox, MD, FAACAP

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000.

Greenhill LL. Diagnosing attention-deficit/hyperactivity disorder in children. J Clin Psychiatry 1998;59(Suppl 7):31-41.


MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group multimodal treatment study of children with ADHD. Arch Gen Psychiatry 1999;56:1073-1086.

Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007;46:894-921.

Treatment Strategies for Childhood ADHD Russell E. Scheffer, MD Barkley R, Fischer M, Edelbrock C, et al. The adolescent outcome of hyperactive children diagnosed by research criteria--III. Mother-child interactions, family conflicts and maternal psychopathology. J Child Psychol Psychiatry 1991;32:233-255.

Barkley R, Guevremont DC, Anastopoulos AD, et al. Driving-related risks and outcomes of attention deficit hyperactivity disorder in adolescents and young adults: a 3- to 5-year follow-up survey. Pediatrics 1993;92:212-218.

Barkley R, Murphy KR, Kwasnik D. Motor vehicle driving competencies and risks in teens and young adults with attention deficit hyperactivity disorder. Pediatrics 1996;98:1089-1095.

Biederman J, Wilens T, Mick E, et al. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics 1999;104:e20.

Brown RT, Pacin JN. Perceived family functioning, marital status, and depression in parents of boys with attention deficit disorder. J Learn Disabil 1989;22:581-587.

Conners CK, Epstein JN, March JS, et al. Multimodal treatment of ADHD in the MTA: an alternative outcome analysis. J Am Acad Child Adolesc Psychiatry 2001;40:159-167.

DiScala C, Lescohier I, Barthel M, Li G. Injuries to children with attention deficit hyperactivity disorder. Pediatrics 1998;102:14,15-21.

Faraone SV, Biederman J, Spencer TJ, Aleardi M. Comparing the efficacy of medications for ADHD using meta-analysis. MedGenMed 2006;8:4.

Fischer M, Barkley R, Edelbrock CS, et al. The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. J Consult Clin Psychol 1990;58:580-588.

Jensen PS, Arnold LE, Swanson JM, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry 2007;46:989-1002.

Leibson CL, Barbaresi WJ, Ransom J, et al. Emergency department use and costs for youth with attention-deficit/hyperactivity disorder: associations with stimulant treatment. Ambul Pediatr. 2006;6:45-53.

Loe IM, Feldman HM. Academic and educational outcomes of children with ADHD. Ambul Pediatr 2007;7(Suppl 1):82-90.

Mannuzza S, Klein RG, Bessler A, et al. Educational and occupational outcome of hyperactive boys grown up. J Am Acad Child Adolesc Psychiatry 1997;36:1222-1227.

Mash EJ, Johnston C. Parental perceptions of child behavior problems, parenting self-esteem, and mothers' reported stress in younger and older hyperactive and normal children. J Consult Clin Psychol 1983;51:86-99.

MTA Cooperative Group. Multimodal treatment study of children with ADHD. Arch Gen Psychiatry 1999;56:1073-1086.

Noe L, Hankin CS. Health outcomes of childhood attention-deficit/hyperactivity disorder (ADHD): health care use and work status of caregivers. Value in Health 2001;4:142-143.

NHTSA. Available at: http://www.nhtsa.dot.gov/.

Pomerleau OF, Downey KK, Stelson FW, et al. Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. J Subst Abuse 1995;7:373-378.

Swanson JM, Kraemer HC, Hinshaw SP, et al. Clinical relevance of the primary findings of the MTA: success rates based on severity of ADH and ODD symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry 2001;40:168-179.

Vitiello B, Severe JB, Greenhill LL, et al. Methylphenidate dosage for children with ADHD over time under controlled conditions: lessons from the MTA. J Am Acad Child Adolesc Psychiatry 2001;40:188-196.

Wilens T, Biederman J, Mick E, et al. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis 1997;185:475-482.

Supplemental Bibliography for: Treatment Strategies for Childhood ADHD Russell E. Scheffer, MD Slide Title: ADHD: Impact of Untreated & Under-Treated ADHD 1. DiScala C, Lescohier I, Barthel M, Li G. Injuries to children with attention deficit hyperactivity disorder. Pediatrics 1998;102:14,15-21.

2. Leibson CL, Barbaresi WJ, Ransom J, et al. Emergency department use and costs for youth with attention-deficit/hyperactivity disorder: associations with stimulant treatment. Ambul Pediatr 2006;6:45-53.

3. NHTSA. Available at: http://www.nhtsa.dot.gov/.

4. Barkley R, Guevremont DC, Anastopoulos AD, et al. Driving-related risks and outcomes of attention deficit hyperactivity disorder in adolescents and young adults: a 3- to 5-year follow-up survey. Pediatrics 1993;92:212-218.

5. Barkely R, Murphy KR, Kwasnik D. Motor vehicle driving competencies and risks in teens and young adults with attention deficit hyperactivity disorder. Pediatrics 1996;98:1089-1095.

6. Fischer M, Barkley R, Edelbrock CS, et al. The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. J Consult Clin Psychol 1990;58:580-588.

7. Mannuzza S, Klein RG, Bessler A, et al. Educational and occupational outcome of hyperactive boys grown up. J Am Acad Child Adolesc Psychiatry 1997;36:1222-1227.

8. Wilens T, Biederman J, Mick E, et al. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis 1997;185:475-482.

9. Pomerleau OF, Downey KK, Stelson FW, et al. Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. J Subst Abuse 1995;7:373-378.

10. Barkley R, Fischer M, Edelbrock C, et al. The adolescent outcome of hyperactive children diagnosed by research criteria--III. Mother-child interactions, family conflicts and maternal psychopathology. J Child Psychol Psychiatry 1991;32:233-255.

11. Brown RT, Pacin JN. Perceived family functioning, marital status, and depression in parents of boys with attention deficit disorder. J Learn Disabil 1989;22:581-587.

12. Mash EJ, Johnston C. Parental perceptions of child behavior problems, parenting self-esteem, and mothers' reported stress in younger and older hyperactive and normal children. J Consult Clin Psychol 1983;51:86-99.

13. Noe L, Hankin CS. Health outcomes of childhood attention-deficit/hyperactivity disorder (ADHD): health care use and work status of caregivers. Value in Health 2001;4:142-143.

Documents

ADHD: Childneurosciencecme.com/library/MM019-day2-1400-mattox...for ADHD Wellbutrin XL 150 150-300 1 Seizures, bulimia, anorexia nervosa, abrupt discontinuation of alcohol or benzodiazepines,