ADHD: Current Update Co-morbidity and Treatment · PDF fileADHD: Current Update Co-morbidity...

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ADHD: Current UpdateCo-morbidity and Treatment Strategies

CADDRA Guidelines

ADHD: Current UpdateCo-morbidity and Treatment Strategies

CADDRA Guidelines

Umesh Jain, M.D., Ph.D.Center for Addiction and Mental Health

and the Hospital for Sick Children

Disclosure StatementDisclosure Statement

Pharmaceutical Company SponsorshipsSponsorships Research Advisory Boards

Eli Lilly X X XGSK X XJanssen-Ortho X X XNovartis X XPurdue Pharma X X XShire Biochem X X XWyeth X X

This talk sponsored by Shire Biochem and Janssen-Ortho

Pharmaceutical Company SponsorshipsSponsorships Research Advisory Boards

Eli Lilly X X XGSK X XJanssen-Ortho X X XNovartis X XPurdue Pharma X X XShire Biochem X X XWyeth X X

This talk sponsored by Shire Biochem and Janssen-Ortho

CADDRACADDRA

A national organization to advocate for all ADHD patients

-physician lead but will soon include key stakeholders

-involved in research, training and advocacy-produced the Canadian ADHD Practice

Guidelines (CAP-Guidelines)

A national organization to advocate for all ADHD patients

-physician lead but will soon include key stakeholders

-involved in research, training and advocacy-produced the Canadian ADHD Practice

Guidelines (CAP-Guidelines)

Executive CADDRAExecutive CADDRA

Sarah Shea AtlanticUmesh Jain Ontario Chair/ AdminLily Hechtman QuebecAnnick Vincent Quebec TrainingDerryck Smith Member at Large AdvocacyAtilla Turgay Ontario GuidelinesDeclan Quinn PrairiesMargaret Weiss BC Research

CADDRA Website and distributionCADDRA Website and distribution

Material will be downloadablewww.caddra.orgwww.caddra.ca

Material can be obtained from industry repsDirect distribution to physicians

(only cost is Postage and Handling)

Material will be downloadablewww.caddra.orgwww.caddra.ca

Material can be obtained from industry repsDirect distribution to physicians

(only cost is Postage and Handling)

Objectives:Objectives:

To review the diagnosis of Attention-Deficit / Hyperactivity Disorder (ADHD) using the CADDRA Guidelines

To review new treatment strategies

To review the diagnosis of Attention-Deficit / Hyperactivity Disorder (ADHD) using the CADDRA Guidelines

To review new treatment strategies

Adult ADHD Studied

19501950 198019801968 19701968 1970 19871987 1994199419371937

Minimal Brain Minimal Brain DysfunctionDysfunction

Minimal Minimal Brain Brain

DamageDamage

Attention Deficit/Hyperactivity Attention Deficit/Hyperactivity Disorder (Disorder (DSMDSM--IIIIII--RR))

Attention Deficit Disorder Attention Deficit Disorder ±±Hyperactivity (Hyperactivity (DSMDSM--IIIIII))

Attention Deficit/Hyperactivity Disorder (Attention Deficit/Hyperactivity Disorder (DSMDSM--IVIV))

Efficacy of Efficacy of AmphetamineAmphetamine

Hyperactive Child Hyperactive Child SyndromeSyndrome

ADHD: Timeline of DefinitionsADHD: Timeline of Definitions

19301930

Hyperkinetic ReactionHyperkinetic Reactionof Childhood (of Childhood (DSMDSM--IIII))

19021902

First First Description of Description of ADHD by StillADHD by Still

Media Hype and ConfusionMedia Hype and Confusion

Myths and FactsMyths and Facts

ADHD is only a childhood disorder and applies only to boys

It is only found in Western countries

It is a behavioral disorderIt reflects inadequate school

funding and that kids are over diagnosed

The medical agenda is being pushed by drug companies

ADHD is only a childhood disorder and applies only to boys

It is only found in Western countries

It is a behavioral disorderIt reflects inadequate school

funding and that kids are over diagnosed

The medical agenda is being pushed by drug companies

ADHD is lifespan disorder and many girls with inattention are not identified

ICD-10 Criteria used elsewhere ADHD is a worldwide

phenomenaIt is a medical disorder that

affects learningThe prevalence rates are 5-9%

though incidence has increased

The MTA study was NIMH funded

ADHD is lifespan disorder and many girls with inattention are not identified

ICD-10 Criteria used elsewhere ADHD is a worldwide

phenomenaIt is a medical disorder that

affects learningThe prevalence rates are 5-9%

though incidence has increased

The MTA study was NIMH funded

Prevalence RatesPrevalence Rates

Prevalence• ~8% of school age children1

• ~50% persistence into adulthood2

• 4.4% of adults meet full criteria for persistent childhood-onset ADHD with significant impairment and comorbidity3

Prevalence• ~8% of school age children1

• ~50% persistence into adulthood2

• 4.4% of adults meet full criteria for persistent childhood-onset ADHD with significant impairment and comorbidity3

1. Faraone SV, et al. World Psychiatry. 2003;2:104-113.2. Faraone SV, et al. Biol Psychiatry. 2000;48(1):9-20.3. Kessler RC. Presenting at: 157th APA Annual Meeting; May 1-6, 2004; New York, NY.

Worldwide Rates of ADHDWorldwide Rates of ADHD

0 5 10 15 20Prevalence of ADHD (%)

Puerto Rico

New York City

Pittsburgh

Tennessee

Minnesota

Oregon

Missouri

Virginia

N. Carolina

NY, MI, WI

Netherlands

New Zealand

Brazil

Ukraine

Germany

Netherlands/Belgium

Switzerland

Israel

United Kingdom

Ireland

Canada

New Zealand

0 5 10 15 20Prevalence of ADHD (%)

(Faraone et al. World Psych:2003)

Southeast Asia

ADHD is impairingADHD is impairing

Coping strategies may limit impairment if the person can find a suitable niche

Impairment can be found in many domains.

“Patients do not meet their potential”

Coping strategies may limit impairment if the person can find a suitable niche

Impairment can be found in many domains.

“Patients do not meet their potential”

Potential Consequences of Untreated ADHD Throughout the Day

Late for Work

Delays Projects Until Deadlines Are Imminent

Forgetful of Things to Be Done

Poor Organization

Easily Bored by Tedious Tasks

Impulsive Job Changes

Work Home

Poor Driving Habits

Frequent Traffic Accidents/ Violations

Low Self-Esteem

Substance Abuse

Fewer Friends

Criminal Activities

Significant Marital Problems

Parenting and Child Care/ Management Difficulties

More Chaotic Family Routines

Poor Financial Management

Poor Housekeeping

Trouble Sustaining Intimate Relationships

7:00 AM

Outside Work/Home

Faraone SV, et al. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 2nd ed. The Guilford Press; 1998:186-224.

5:00 PM 7:00 PM

Long-term Educational ImpairmentLong-term Educational Impairment

0 10 20 30 40 50 60 70

Grade retention

Suspension

Expulsion

Drop-out

Did not graduatecollege Control

% of SampleBarkley RA. J Clin Psychiatry. 2002;63(suppl 12):10-15.

Occupational ImpairmentOccupational Impairment

0.0 0.5 1.0 1.5 2.0 2.5 3.0

ControlADHD

0.0 0.5 1.0 1.5 2.0 2.5 3.0

ControlADHD

Odds RatioBarkley RA. J Clin Psychiatry. 2002;63(suppl 12):10-15

Change JobsMore Often

More Likely toBe Fired

ADHD Classifications- DSM-TRADHD Classifications- DSM-TR

ADHD, Predominantly Combined Subtype (ADHD-C)- >50%

ADHD, Predominantly Inattentive Subtype (ADHD-I) 35%

ADHD, Predominantly Hyperactive-Impulsive Subtype (ADHD-HI) <10%

ADHD, Predominantly Combined Subtype (ADHD-C)- >50%

ADHD, Predominantly Inattentive Subtype (ADHD-I) 35%

ADHD, Predominantly Hyperactive-Impulsive Subtype (ADHD-HI) <10%

CADDRA Feedback FormPresented to family so they know

how the diagnosis was made

CADDRA Feedback FormPresented to family so they know

how the diagnosis was made

Impairment ScalesWFIRS – review domains of functioning

Assessment Algorithm for ADHDAssessment Algorithm for ADHD

Documentation using the CADDRA Child and Adolescent TemplateInclusion Strategies also include:

Family HistoryChildhood History (also school report cards and other assessments)

Exclusion StrategiesCADDRA Co-morbidity Scales (Turgay) or Checkmate Plus

Documentation using the CADDRA Child and Adolescent TemplateInclusion Strategies also include:

Family HistoryChildhood History (also school report cards and other assessments)

Exclusion StrategiesCADDRA Co-morbidity Scales (Turgay) or Checkmate Plus

ScreeningDSM-TR + SNAP Questionnaires (ensure referral for psychometrist)

ADHD etiology: No simple solutionsADHD etiology: No simple solutions

Behavioralhyperactivityimpulsivity

• CognitiveInattentionConcentrationMemory

• Socialisolationrejectionasocialantisocial

• EmotionalTemperAffect regulationMood problems

Biological Evidence for ADHDBiological Evidence for ADHD

PET StudiesCognitive DataNeuro-chemical evidenceGenetic Data

Prepubescent Growth Spurt in Cortex(thickens just before puberty, then thins)

J. Giedd (2003) NIMH

Aggregate of 52 MRI scaof normal kids scanned X@ 2 yr intervalsCortex thickness peaks a11 yo in females12.5 in malesThen prunes for More efficient circuits

[View of right orbital lateral cortex; blue is thinner]

Positron Emission Tomography (PET) studies show that methylphenidate acts predominantly in the striatum of the human brain where it binds

to DA transporters

[11C]methylphenidate

methylphenidate

Extensive PET studies of Methylphenidate in the Human Brain

Volkow et al. J Atten Disord 2002

Ritalin improves glucose consumption in the brain

ADHD: Decreased consumptionIncreased consumption with Ritalin

Faraone. J Am Acad Child Adolesc Psychiatry. 2000;39:1455-1457. Hemminki. Mutat Res. 2001;25:11-21.Palmer. Eur Resp J. 2001;17:696-702.

Willerman, 1973Goodman, 1989

Gillis, 1992Edelbrock, 1992

Schmitz, 1995Thapar, 1995Gjone, 1996

Silberg, 1996Sherman, 1997

Levy, 1997Nadder, 1998

Hudziak, 2000

Average genetic contribution of ADHD based on twin studies0 0.2 0.4 0.6 0.8 1

HeightBreast cancer Asthma Schizophrenia

Twin Studies ADHD Is Genetically BasedTwin Studies ADHD Is Genetically BasedADHD Mean

The Dopamine ConnectionThe Dopamine Connection

Convincing clinical evidence of stimulant responsiveness (possible self medication with THC and cocaine)

Cognitive changes that show normalization of inhibitory control (Stopsignal paradigm test) and alteration in blood flow on PET scanning

Genetic findings point to possible dopamine factors

Convincing clinical evidence of stimulant responsiveness (possible self medication with THC and cocaine)

Cognitive changes that show normalization of inhibitory control (Stopsignal paradigm test) and alteration in blood flow on PET scanning

Genetic findings point to possible dopamine factors

Dopamine Neurotransmission Dopamine Neurotransmission

Enhances signalImproves attention

• Focus• On-task behavior• On-task cognition

Enhances signalImproves attention

• Focus• On-task behavior• On-task cognition

Solanto. Stimulant Drugs and ADHD. Oxford; 2001.

NigrostriatalPathway

MesolimbicPathway

Substantianigra

Ventral tegmentalarea

MesocorticalPathway

DopamineDopamine

Noradrenaline ConnectionNoradrenaline Connection

Part of the same catecholamine pathway

If the only way to keep your brain on is to create crisis, activation of noradrenaline

Alteration in arousal

Helped with noradrenaline based medication

Part of the same catecholamine pathway

If the only way to keep your brain on is to create crisis, activation of noradrenaline

Alteration in arousal

Helped with noradrenaline based medication

Locus Ceruleus

Frontal

Limbic

Noradrenaline Neurotransmission Noradrenaline Neurotransmission

• Dampens noise• Executive operations• Increases inhibition

Solanto. Stimulant Drugs and ADHD. Oxford; 2001.

NoradrenalineNoradrenaline

Mechanism of Action- NA AgonistsMechanism of Action- NA Agonists

1. Data on File: Eli Lilly and Company.2. Adapted from Bymaster FP, et al. [Poster] 58th Annual SOBP Meeting, 15-23 May 2003, San

Francisco, California.

Atomoxetine

v v Storagevesicle

DA Transporter

Cytoplasmic DA

Methylphenidate blocks

reuptake

PresynapticPresynaptic NeuronNeuron

SynapseSynapse

Wilens T, Spencer TJ. Handbook of Substance Abuse: Neurobehavioral Pharmacology. 1998;501-513.

Amphetamine blocks

reuptake

Amphetamine blocks

Mechanism of Action of StimulantsMechanism of Action of Stimulants

Multimodal Treatment of ADHD (MTA) StudyMultimodal Treatment of ADHD (MTA) Study

This trial randomized 579 children aged 7-9 years to one of four treatment arms over 14 months: 1. Monthly management of medication treatment with supportive care2. Intensive behavioural treatment3. Medication plus supportive care and intensive behavioural treatment4. Usual community care (most cases with medication, not closely monitored) 5. Follow up for ten years

MTA group, Arch Gen Psychiatry 1999;56:1073-1086

This trial randomized 579 children aged 7-9 years to one of four treatment arms over 14 months: 1. Monthly management of medication treatment with supportive care2. Intensive behavioural treatment3. Medication plus supportive care and intensive behavioural treatment4. Usual community care (most cases with medication, not closely monitored) 5. Follow up for ten years

MTA group, Arch Gen Psychiatry 1999;56:1073-1086

Parent SNAP-Hyp/Impulsive

0 100 200 300 400

MedMgt

Time x Tx: F=21.5, p<.0001Site x Tx: F=1.3, nsSite: F=4.4, p<.0006

Comb, MedMgt > Beh, CC

Assessment Point (Days)

Teacher SNAP-ODD/Aggressive

0 100 200 300 400

MedMgt

Time x Tx: F=6.5, p<.0003Site x Tx: F=1.2, nsSite: F=4.2, p<.001

Comb, MedMgt > CC

Assessment Point (Days)

CADDRA RecommendationsCADDRA Recommendations

Long acting agents will be first line• Across the lifespan but particularly for adolescents and

adultsShort acting agents will be considered adjuvant treatments in the first line

Long acting agents will be first line• Across the lifespan but particularly for adolescents and

adultsShort acting agents will be considered adjuvant treatments in the first line

The Need for Once-Daily Dosage OptionsThe Need for Once-Daily Dosage Options

Extended medication coverage needed• After school, extracurricular activities• Social interactions• Homework hours

Problems with in-school dosing• Privacy issues

• Ridicule by peers; decreased self-esteem• Storage of controlled medications

• Security; potential for diversion

Extended medication coverage needed• After school, extracurricular activities• Social interactions• Homework hours

Problems with in-school dosing• Privacy issues

• Ridicule by peers; decreased self-esteem• Storage of controlled medications

• Security; potential for diversion

ADHD Medications (in alphabetical order)ADHD Medications (in alphabetical order)

CADDRA guidelines-information downloadable-useful for parents and adolescents

SE suggestions also listed

CADDRA guidelines-information downloadable-useful for parents and adolescents

SE suggestions also listed

ADDERALL XR™ (Dextroamphetamine Salts)ADDERALL XR™ (Dextroamphetamine Salts)

Adderall XR is registered in the US patent and trademark office. Slide provided by Shire Biochem.

Adderall XR™ ProfileAdderall XR™ Profile

50% at the beginning8-12 hr durationSprinkle formulationEfficacy and safety established #1 selling ADHD medication worldwideMultiple doses make it easy to titrateBroad indications- all age groups in the US

Supplied by Purdue Pharma

Biphentin® ProfileBiphentin® Profile

40/60 delivery systemControlled release patented technologySeven doses – easy exchange to t.i.d. dosingSprinkle formatMade in Canada and available only in Canada10-12 hour durationActive ingredient well established efficacy and safetyIndicated in all age groups (including adults)

CONCERTA® (methylphenidate)CONCERTA® (methylphenidate)

MPH Overcoat

Tablet Shell

Push Compartment

MPH Compartment

Laser-Drilled Hole

MPH Compartment

Slide provided by Janssen-Ortho. Concerta® is a registered product. Using the OROS® technology.

Concerta ™ ProfileConcerta ™ Profile

22% delivery then 78% release8-12 hr durationFew formulations (4 doses) but easy to titrate

5 tid = 18, 10 tid = 36, 15 tid = 54Covered by Ontario and Quebec limited accessEstablished efficacy and safety

22% delivery then 78% release8-12 hr durationFew formulations (4 doses) but easy to titrate

5 tid = 18, 10 tid = 36, 15 tid = 54Covered by Ontario and Quebec limited accessEstablished efficacy and safety

STRATTERA® (atomoxetine)STRATTERA® (atomoxetine)

Slide provided by Eli Lilly. Strattera® is a registered product by Eli Lilly.

STRATTERA® Profile

24 hour coverageSamples availableMaintains a blood level and dosing can be adjustedLimited Access Coverage in Ontario and in PQ Multiple dosesCost no different than most antidepressantsNon-controlled substanceSide effects limited with slower titration

Slide provided by Eli Lilly. Strattera® is a registered product by Eli Lilly.

Syndrome of ADD Impairmentsis involved in most disorders

Disorders of Executive FunctionsDeveloped or Acquired

Language & LearningExp Lang

Recep Lang

Reading LD

Math LD

Written Exp LD

Arousal & MotivationDysth/Depression

Anxiety

Bipolar

Substance Abuse

Social-Emotional RegulationAsperger’s

Autism/PDD

Conduct

Tourette’s

Impairments of EF involved in all of these

Used by permission, Tom Brown, CADDRA meeting June 2006

ADHD Co-morbidityADHD Co-morbidity

PSUD Anxiety MDD LD BipolarDisorder

Lifetime Comorbid Disorders + ADHDLifetime Comorbid Disorders + ADHD

MDD=major depressive disorder. LD=learning disability. ASP=antisocial personality disorder.Shekim WO, et al. Compr Psychiatry. 1990;31(5):416-425.Biederman J, et al. Am J Psychiatry. 1993;150(12):1792-1798.

Oppositional Defiant DisorderOppositional Defiant Disorder

Driven by the ADHDReflective of environmental insecurityCultural

If driven by ADHD, treatment of ADHD will lessen the ODD symptoms

Driven by the ADHDReflective of environmental insecurityCultural

If driven by ADHD, treatment of ADHD will lessen the ODD symptoms

Holistic InterventionsHolistic InterventionsThe medications are there to facilitate the other interventions• Behavioral• Psychological• School- Educational• Social

The medications are there to facilitate the other interventions• Behavioral• Psychological• School- Educational• Social

CONTACT INFOCONTACT INFO

CADDRA- heidi.bernhardt@caddra.comumesh_jain@camh.net

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