adhd: current update co-morbidity and treatment strategies caddra
TRANSCRIPT
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
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
Iowa
Tennessee
Minnesota
Oregon
Missouri
Virginia
N. Carolina
NY, MI, WI
China
Netherlands
New Zealand
Japan
Brazil
Ukraine
Germany
Netherlands/Belgium
Switzerland
Israel
United Kingdom
Ireland
Canada
New Zealand
Spain
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
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
ADHD
% 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
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)
ScreeningDSM-TR + SNAP Questionnaires (ensure referral for psychometrist)
ADHD etiology: No simple solutionsADHD etiology: No simple solutions
Behavioralhyperactivityimpulsivity
Behavioralhyperactivityimpulsivity
• CognitiveInattentionConcentrationMemory
• Socialisolationrejectionasocialantisocial
• EmotionalTemperAffect regulationMood problems
Biological Evidence for ADHDBiological Evidence for ADHD
PET StudiesCognitive DataNeuro-chemical evidenceGenetic Data
PET StudiesCognitive DataNeuro-chemical evidenceGenetic Data
Prepubescent Growth Spurt in Cortex(thickens just before puberty, then thins)
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
Extensive PET studies of Methylphenidate in the Human Brain
Volkow et al. J Atten Disord 2002
Ritalin improves glucose consumption in the brain
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
0.5
1
1.5
2
2.5
3
0 100 200 300 400
CC
Beh
MedMgt
Comb
Time x Tx: F=21.5, p<.0001Site x Tx: F=1.3, nsSite: F=4.4, p<.0006
Comb, MedMgt > Beh, CC
Ave
rage
Sco
re
Assessment Point (Days)
Teacher SNAP-ODD/Aggressive
0
0.5
1
1.5
2
2.5
3
0 100 200 300 400
CC
Beh
MedMgt
Comb
Time x Tx: F=6.5, p<.0003Site x Tx: F=1.2, nsSite: F=4.2, p<.001
Comb, MedMgt > CC
Ave
rage
Sco
re
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
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)
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
#2
Laser-Drilled Hole
MPH Compartment
#1
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
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
PTSD
Bipolar
OCD
Substance Abuse
Social-Emotional RegulationAsperger’s
Autism/PDD
ODD
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
0
10
20
30
40
50
60
PSUD Anxiety MDD LD BipolarDisorder
ASP0
10
20
30
40
50
60
PSUD Anxiety MDD LD BipolarDisorder
ASP
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.
Prev
alenc
e (%
)
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
