Trattamenti dell’ADHD bambino - EURAC research dell’ADHDnel bambino ... affects computation in...

Psichiatria di TransizioneLa complessità dell’ADHD

Bolzano , 5-6 dicembre 2016

Trattamenti dell’ADHD nel bambino

Alessandro ZuddasClinica di Neuropsichiatria dell’Infanzia e dell’Adolescenza

Sezione di Neuroscienze e Farmacologia ClinicaDipartimento di Scienze Biomediche, Università di Cagliari

Ospedale Pediatrico “A. Cao”, AO “G.Brotzu”, Cagliari

AO Brotzu

Financial Disclosure (2013-2016)

Research grants• Shire• Vifor• Roche• Lundbeck• EU 7 Framework Program (PERS, STOP, ADDUCE, MATRICS)• AIFA-Farmacovigilanza (Agenzia Italiana del Farmaco), • Assessorato Sanità Regione Sardegna

RoyaltiesGiunti.OS, Oxford University Press

Speaker or advisory relationship with: Angelini, Lilly, Otsuka, Shire, Takeda, Vifor.

Member of Data Safety Monitory BoardsOtsuka, Lundbeck,

Genes & Environment

Genes & Environment

Brain Structure and Function


Cognition

(executive functions)

Cognition


Symptoms and Impairment


Traditional view of causal pathway to ADHD

GenesGenesBrain Structure and Function


CognitionCognition

SymptomsSymptoms

ImpairmentImpairment

Alternative view of causal pathway to ADHD


ADHD, executive functions & Neuro-economic models

Psychological intervention

Effect of Medications

Clinical implications

Decision Making: a neuro-economic model

JCPP Sonuga-Barke et al. 2016

Evaluation Decision &Managemnent

Appraisal &Accomodation

Self referential(Default Mode Network-DMN)

Reducte integrity of DMN: impaired prospection

DMN interference linked to attentional laspes

Executive Dorsal fronto-striatal / fronto-parietal deficits reduce decision speed & efficiency

Reinforcement Ventral fronto-striatal deficits impair utility estimate and with Delay adversion produce preference for immediacy

Disconnectivity inOrbito-frontal Ctxaffects computation in predicting errors , impairing learning

ADHD Neuroeconomic Model:Inefficiency, inconsistency, impulsiveness

Sonuga-Barke et al. JCPP 2016

Deficit delle funzione esecutivenei bambini con disturbo da deficit di attenzione e iperattività

ADHD is an heterogeneous disorder

ADHD & executive functions

Neuro-economic models




Inclusion criteria

Age 3-18Diagnosis ADHD ( any subtype)Symptom measured by validated rating ScaleAppropriate control groupStable medication allowed (sensitivity analysis)Rare comorbidity (i.e. Fragile X) excluded

Outcome measure : ADHD symptoms scaleMost proximal assessmentProbably blinding assessment

Study quality independently assessed (Jadad et al. criteria for randomization,

blinding and missing data)

Misure di efficacia delle terapie

Effect Size

Basaline EndPoint

Farmaco 38.5 + 5.8 25.5 + 4.2

Placebo 40.4 + 6.1 32.7 + 5.0

d= (38.5-25.5) - (40.4-32.7) = 13.0 -7.7 = ES 1.1

(4.2+5.0)/2 4,6

Differenza nei cambiamenti dal baseline tra due trattamenti (es. farmaco

e placebo), diviso la media delle dev. standard (es. placebo e farmaco ad

end point).

L’effect size standardizza le unità di misura nei diversi studi.

Secondo la definizione di Cohen, ES > 0.2 è considerato basso,

ES > di 0.5 è considerato medio; oltre 0.8 è considerato alto

ES in General Medicine

Aspirine for prevention cardiovascular disease 0.06

Antypertensive on long term mortality 0.11

Corticosteroids for asthma 0.54

Antypertensive for high blood pressure 0.55

Interferone for Chronic Hepatitis C 2.27

ES in General (Adult) Psychiatry

SGA for schizophrenia (PANS) 0.51

SSRI for depression (HAMD) 0.32

SSRI/ Bdz for Panic 0.41

SSRI for OCD 0.44

Leucht et al.2012

ADHD

Intervention Most proximal assessment (SMD)

Probably blinding assessment (SMD)

Restricted EliminationDiet

1.48 0.51

Artificial food color exclusion

0.32 0.42

Free fatty acid supplementation

0.21 0.16

Cognitive training 0.64 0.24

Neurofeedback 0.59 0.29

Behavioral intervention 0.40 0.02

Sonuga-Barke et al. AJP 2013

MPROX PBLIND

Sonuga-Barke et al. AJP 2013

Behavioral interventions in attention-deficit/hyperactivity

disorder: a meta-analysis of randomized controlled trials across multiple outcome domains. Daley et al. JAACAP 2014

Dimension MPROX PBLIND

Positive parenting 0.68 0.63

Negative parenting 0.57 0.43

Parental self-concept 0.37

Parental Mental Health 0.09

Dimension MPROX PBLIND

ADHD 0.35 0.02

Conduct problem 0.26 0.31

Social skills 0.47

Academic Achievement 0.28

JAACAP 2015

Deficit delle funzione esecutivenei bambini con disturbo da deficit di attenzione e iperattività


ADHD & executive functions

RDoC & neuro-economic models


Effects of Medications


Biological Psychiatry 2007

Biological Psychiatry 2009

Pharmacotherapy for ADHD

Stimulants

Methylphenidate

Amphetamine compounds

Atomoxetine

Guanfacine

Antihypertensive

Clonidine

Antidepressant

Tricyclics

Bupropion

Investigational

AcethylCholine (Nicotine) (Chan NPF

2007)

Glutamate: Ampakine

Histamine: H3 antagonists (Esbenshade BJF 2008)

Serotonine: 5HT 7 Agonists

Omega 3/6

More pharmacological treatment options are available in North America than in Europe

Generic dexamphetamine is available in Europe

Adderall

Dexedrine

Dextrostat

Vyvanse/Elvanse

Adderall XR

Dexedrine spansules

Ritalin

Desoxyn

FocalinMethylin

Daytrana

Medikinet

Concerta XL

MedikinetXL

Focalin XR

Metadate CD /Equasym XLMethylin ER

Ritalin SR

Ritalin LA

Quillivant XR

Strattera

Intuniv

Kapvay

Brands available in North America

Brands available in Europe

Amphetamine

Methylphenidate

Non-stimulants

More pharmacological treatment options are available in North America than in Europe

Generic dexamphetamine is available in Europe

Adderall

Dexedrine

Dextrostat

Vyvanse/Elvanse

Adderall XR

Dexedrine spansules

Ritalin

Desoxyn

FocalinMethylin

Daytrana

Medikinet

Concerta XL

MedikinetXL

Focalin XR

Metadate CD /Equasym XLMethylin ER

Ritalin SR

Ritalin LA

Quillivant XR

Strattera

Intuniv

Kapvay

Brands available in North America

Brands available in Europe

Amphetamine

Methylphenidate

Non-stimulants

In Italia

Stimulants mechanism of action

Methylphenidate Decreased the Amount of Glucose Needed by the Brain to Perform a Cognitive Task Volkow et al., 2008

Nach Seamans et al. J Neurosci 2001

What is the action of dopamine on

prefrontal cortex ?Optimal D1-receptor activity stateSuboptimal D1-receptor activity state

Optimal signal-to-noise ratio

in interaction with other neurotransmitter systems

Effect of MPH on cognitive tasks

Volkow et al. 2004

Volkow & Swanson AJP 2003

Task‐related default mode network modulation

and inhibitory control in ADHD:

effects of motivation and methylphenidate

Liddle et al. 2011

Volkow & Swanson AJP 2003

Formulation for extended release:

Osmotic Pump (Concerta XL®) o coated beads (Equasym XL® CD)

Tablet

Shell

Push

Compartme

nt

MPH

Compartme

nt

#2

Laser-Drilled

Hole

MPH

Compartment

#1

IR MPH uncoated beads

ER MPH coated beads

Immediate Release (IR) MPH

IR MPH overcoat

Two ER MPH

reservoirs

Extended Release (ER) MPH

Efficacia degli interventi per l‘ADHD Lo studio MTA

MTA Cooperative GroupArch. Gen. Psychiatry 1999

Arnold et al. AJP 1997

EFFICACIA DEGLI INTERVENTINormalizzazione sintomatica nello studio MTA

25

34

56

68

0

10

20

30

40

50

60

70

80

Percentuale

Trattamento

standardMED MED + CBTCBT

+

DIAGNOSI SECONDO ICD-10 (HKD)DIAGNOSI SECONDO ICD-10 (HKD)

Disturbo ipercineticoDisturbo ipercineticoInattenzioneInattenzione IperattivitàIperattività ImpulsivitàImpulsività+ +

Disturbo ipercinetico

della condotta

Disturbo ipercinetico

della condottaDisturbo della condottaDisturbo della condotta

DIAGNOSI SECONDO DSM-IV (ADHD)DIAGNOSI SECONDO DSM-IV (ADHD)

ADHD: tipo combinatoADHD: tipo combinatoInattenzioneInattenzione Iperattività/impulsivitaIperattività/impulsivita+

ADHD: tipo prevalentemente inattentivo

ADHD: tipo prevalentemente inattentivo

Solo inattenzioneSolo inattenzione

ADHD: tipo prevalentemente

iperattivo/impulsivo

ADHD: tipo prevalentemente

iperattivo/impulsivoSolo iperattività/impulsivitàSolo iperattività/impulsività

ADHD (DSM-IV) vs HKD (ICD-10)

ICD-10 DIAGNOSIS

579 ADHD - Combined

Without Anxiety/Depression432

Pervasive161

Borderline ADHD 71

Anxiety/Depression147

3 Symptom domains361

Home -P134

School -P66

Impairment

HKD 145

ADHD vs HKDSNAP Hyperactivity-Impulsivity (Parent)

Farmaci non stimolanti: Atomoxetina

• Inibitore altamente selectivo del reuptake della Noradrenalina (Ki=4 nM)

• Basa affinità per altri siti di reuptake per altri neurotransmettitori.

Kratochvil CJ, et al. J Child Adolesc Psychopharmacol 2001;11:167-70; Michelson D, et al. Pediatrics 2001;108:E83; Spencer T, et al. J Child Adolesc Psychopharmacol 2001;11:251-65.

CH3

O NCH3

H

HCl

CH3

O NCH3

H

HCl

Atomoxetine mechanism of actionAtomoxetine mechanism of action

DOPAMINERGIC

Neuron

Presynapsis Post-synapsis

DA

DADA

DA

DA

DOPADOPAdecarbossilase

HVA

DAT

RR

DOPA DA NA

NA

NA

NA

NA

NA Transporter

R RDopamina-bidrossilase

MHPG

DOPAdecarbossilase

NORADRENERGIC

Neuron

MAO

MAO

Receptors

Homovanillic AcidHVA

Dopamine transporter

3-metossi-4-idrossifenilglicoleMHP

G

MonoaminoossidaseMAO

3,4-diidrossifenilalanineDOPA

Dopamine

NoradrenalineNA

DA

DAT

HVA

Prefrontal cortex (3 mg/kg)

Nucleus accumbens (3 mg/kg)Striatal dopamine (10 mg/kg)

Time (Hours)

-1 0 1 2 3 4

% D

op

amin

e B

asel

ine

0

50

100

150

200

250

300

350

Time (Hours)

-1 0 1 2 3 4

% D

op

amin

e B

asel

ine

0

50

100

150

200

250

300

350

Prefrontal cortex

Nucleus accumbensStriatum

Atomoxetine and Methylphenidate: Effects on Extracellular Dopamine in

Rat Prefrontal Cortex, Nucleus Accumbens, and Striatum

Bymaster FP, et al. Neuropsychopharmacology 2002; 27( 5): 699–711.

AtomoxetineMethylphenidate

Methylphenidate 3 mg/kg ip Atomoxetine 1 mg/kg ip

Dissociable effects of methylphenidate, atomoxetine and placebo on regional cerebral blood flow in healthy volunteers at rest: A multi-

class pattern recognition approach

Marquand et al. NeuroImage 2012

Atomoxetine Relapse Prevention study

Period II

Acute Treatment

Period III

Double-Blind Relapse Prevention

atomoxetine(n=604)

1 Wk 58 Wks

Period I

Screening& Evaluation

10 Wks 2 Wks

placebo (n=124)

ATX (n= 292)ATX (n=81)

placebo (n=82)40 Wks

J. Buitelaar, M. Danckaerts, C. Gillberg, A. Zuddas, et al.A prospective, multicenter, open-label assessment of atomoxetine in non-Northern American children and adolescent with ADHD. Eur. Child Adolesc. Psychiatry, 13: 249-257; 2004

D. Michelson, J. Buitelaar, M. Danckaerts, C. Gillberg,TJ. Spencer, A. Zuddas, D. Faries, S. Zhang, J. Biederman, Relapse Prevention in Pediatric Patient with ADHD Treated with Atomoxerine: Randomized Double-blind, Placebo-Controlled Study J. American Acad. Child Adolesc.Psychiatry, 43: 896-904; 2004

J. Buitelaar, D. Michelson, M. Danckaerts, C. Gillberg, T Spences, A. Zuddas, DE Faries, S. Zhang, J.BiedermanA Randomized, Double-Blind Study of Continuation Treatment for ADHD After One Year Biological Psychiatry, 61: 694-699; 2007

Atomoxetine Relapse Prevention study

atomoxetine(n=604)

1 Wk 58 Wks10 Wks 2 Wks

placebo (n=124)

ATX (n= 292)

ATX (n=81)

placebo (n=82)40 Wks

41,3

18

0

10

20

30

40

50

Baseline Endpoint

AD

HD

RS

Me

an

To

tal

Sc

ore

p < .001

Buitelaar ECAP 2004 Days to Relapse

0 25 50 75 100 125 150 175 200 225 250 275

Pro

po

rtion

No

t Re

lap

sin

g

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Placebo

Atomoxetine

Michelson JAACAP 2004

Buitelaar Biol.Psych. 2006

MPH-ER vs. ATXComparazione diretta

Based on direct comparisons, reviews by NICE concluded that there is little difference in efficacy between IR-MPH, ER-MPH, ATX

* Significantlydifferent from placeboP

erc

en

t R

esp

on

der

s

0

10

20

30

40

50

60

70

80

ATMXOROS® MPHPlacebo

P=.016P=.423

P=.026

All Patients(N=492)

Prior Stimulant Users(N=301)

Stimulant Naïve(N=191)

45%

37%

56%

24% 23%

51%57%

64%

25%

*

**

**

Responder: 40% Reduction From Baseline in ADHD RS Total Symptom Score

Michelson, 2004

Efficacia: Effect Size

Basaline EndPoint

Farmaco 38.5 + 5.8 25.5 + 4.2

Placebo 40.4 + 6.1 32.7 + 5.0

d= (38.5-25.5) - (40.4-32.7) = 13.0 -7.7 = ES 1.1

(4.2+5.0)/2 4,6

Differenza tra i cambiamenti dal baseline tra farmaco e placebo,

diviso la media delle dev. standard (placebo e farmaco ad end point).

L’effect size standardizza le unità di misura nei diversi studi.

Secondo la definizione di Cohen, ES > 0.2 è considerato basso,

ES > di 0.5 è considerato medio; oltre 0.8 è considerato alto

EfficaciaEffect Sizes sui sintomi di ADHD

• Effect size = difference in outcome scores between drug and placebo groups divided by the pooled standard deviation

• Caveat: Effect size might be influenced by design features (e.g., different types of rater, durations of studies, dosing regimens)

Effect Size: MPH-IR = MPH-ER (approx 1) > ATX, Modafinil (approx 0.7)

Parent Teacher Clinician

SMDNo. of studies

(rating scales

used)SMD

No. of studies

(rating scales

used)SMD

No. of studies

(rating scales

used)References

Adderall XR 0.9 1 1.1 1 1.2 1 Data on file Shire

Concerta XL 1.0 1 1.0 1 Wolraich et al.

Equasym XL 0.6 2 0.9 1 1.8 1 Greenhill et al.

Swanson et al.

Findling et al.

Medikinet

retard1.0 1 1.0 1 0.9 1 Döpfner et al.

Ritalin LA 1.0 1 Biederman et al.

ATX 0.7 6 0.7 11 Data on file Eli

Lilly

Modafinil 0.6 3 0.7 3 Data on file

Cephalon

Numbers needed to treat =

100% / (% migliorato col

farmaco – % i migliorato

con Placebo)

Esempio:

Numbers Needed to Treat

= 100 / (75 – 25)

= 100 / 50

= 2

Maggiore la differenza,

minore il numero

Percentuale di patienti normalizzati

Active

treatment

100

75

0

50

100

0

Placebo

25

Efficacia: Number Needed to Treat (NNT)

Efficacia (Numbers Needed to Treat)

NNT: MPH-IR = MPH-ER = ATX (c. 3–5)

*Caveat: Normalisation data may be influenced by an inadequate study design (e.g. Concerta

data)

Medication% normalised

active med

% normalised

placebo

Number needed to

treat (95% CI)

MPH IR 41 20 4.8 (±0.15)

Adderall XR 51 25 3.8 (±0.14)

Concerta XL * 66 14 1.9 (±0.20)

Equasym XL 39 20 5.3 (±0.15)

Medikinet

retard49 12 2.7 (±0.18)

Atomoxetine 42.3 18.5 4.2 (±0.07)

JAACAP 2014

Teacher rating of ADHD symptoms

Symptoms ES: 0.77

QoL ES: 0.87

No risk for serious adverse eventsRR: 0.98

Minor risk for non-serious adverse events

RR: 1.29

ES in General Medicine

Aspirine for prevention cardiovascular disease 0.06

Antypertensive on long term mortality 0.11

Corticosteroids for asthma 0.54

Antypertensive for high blood pressure 0.55

Interferone for Chronic Hepatitis C 2.27

ES in General Psychiatry

SGA for schizophrenia (PANS) 0.51

SSRI for depression (HAMD) 0.32

SSRI/ Bdz for Panic 0.41

SSRI for OCD 0.44

Leucht et al.2012

Efficacia a lungo termine delle terapie Normalizzazione sintomatica nello studio MTA

25

34

56

68

0

10

20

30

40

50

60

70

80

Percentuale

Trattamento

standard

MED MED + CBTCBT

Efficacia a lungo termine delle terapie (studio MTA)

Sintomi di ADHD

0

0,5

1

1,5

2

2,5

0 1 2 3

Comb

Med

Beh

CC

YearsJensen et al. JAACAP 2007

EFFICACIA DEGLI INTERVENTI

Diagnostic Status

0

20

40

60

80

100

120

0 1 2 3

ADHD

0

20

40

60

80

100

120

0 1 2 3

Comb

Med

Beh

CC

ODD

Jensen et al. JAACAP 2007

Percentuale di bambini che assumevano farmacinelle diverse fasi dello studio MTA


Years

Treatment 0 1 2 3

Comb 20 90 70 71

Med 22 90 70 71

Beh 19 14 35 43

CC 20 60 62 62

MTA study follow up

0

20

40

60

80

100

120

0 1 2 3

ADHD

0

20

40

60

80

100

120

0 1 2 3

Comb

Med

Beh

CC

ODD


0

0,5

1

1,5

2

2,5

0 1 2 3

Comb

Med

Beh

CC

0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

0 1 2 3

Comb

Med

Beh

CC

Symtoms

Diagnostic status

Secondary evaluation of MTA 36-month outcome:

propensity score and growth mixed model analysis

0

0,5

1

1,5

2

2,5

0 1 2 3

Class 1

Class 2

Class 3

LNCG

ADHD: SNAP score

YearsSwanson et al. JACAAP 2007

Secondary evaluation of MTA 36-month outcome: propensityscore and growth mixed model analysis

Swanson et al. JACAAP 2007

Secondary evaluation of MTA 36-month outcome: propensity score and growth mixed model analysis

Swanson et al. JACAAP 2007

The MTA at 8 Years: Prospective Follow-up of ChildrenTreated for Combined-Type ADHD in a Multisite Study

Molina et al. JACAAP 2009

Nakao et al. AJP 2011

November 22, 2012 Vol. 367 No. 21

Planning (Stockings of Cambridge)

Set Shifting(ID/ED)

ADHD

ADHD

Controls

Controls

Change in executive functioning (planning and set shifting) over a four year period

8,9

8,9

7,8

6,9

8,1

9,5

6,9

7

0 2 4 6 8 10

ADHD Time 1 ADHD Time 2

Controls Time 1 Controls Time 2

*

*

*

*

E.S.

1.4

1.1

1.7

1.0

Coghill et al 2013 Psychological Medicine

Spatial Working Memory(Between

Search Errors)

ADHD

ADHD

Controls

Controls32,6

29

34,9

47,9

33,8

33,5

37,2

56,6

0 10 20 30 40 50 60



*

*

*

*

Spatial Working Memory(Strategy

Score)

Change in executive functioning (spatial working memory) over a four year period

E.S.

1.1

1.0

0.7

0.4


Delayed Matching to

Sample(% correct)

ADHD

ADHD

Controls

Controls

Change in non executive functioning (recognition memory) over a four year period

79,7

90,4

84,1

72,9

88,5

71

68,2

92,4

75,7

66,5

80,4

60

0 20 40 60 80 100



*

*

*

*Controls

ADHD

Pattern Recognition(% correct)

Spatial Recognition(% correct)

E.S.

0.9

0.8

0.9

0.6


Lisdexamfetamina (LDX)

NH

O

H2N

CH3

NH2

Site of Cleavage

H2N

O

H2NCH3

NH2

OH

+

NRP104 l-lysine d-amphetamine

Placebo(n = 106)

Lysdexamfetamine: change in ADHD-RS-IV total score

p-values and effect sizes are from an ANCOVA model of the change in ADHD-RS-IV total score from baseline to endpoint. ANCOVA, analysis of covariance; SD, standard deviation

LDX(n = 104)

OROS-MPH(n = 107)

−20

Baseline (mean ± SD)

Endpoint (mean ± SD)

LS mean change (± SE)

AD

HD

-RS-

IV t

ota

l sco

re

40.7 41.0 40.534.8 21.716.0

−5.7

−30

−10

0

10

20

30

40

50

−24.3 −18.7

p < 0.001Effect size: 1.80

p < 0.001Effect size: 1.26

Full analysis set

N = 317

Coghill et al. ENP 2013

JAACAP 2014

Maintenance of efficacy of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivitydisorder: randomized-withdrawal design Coghill et al. JAACAP 2014

Primary Outcome relapses during the randomized withdrawn

Randomized full analysis set

Cu

mu

lati

ve p

rop

ort

ion

of

trea

tmen

t fa

ilure

s (%

)***

V4R V5R V6R V7R V8R V9R EndpointW27 W28 W29 W30 W31 W32

0

20

40

60

80

100

***p < 0.001 active drug versus placebo≥ 50% increase in ADHD-RS-IV total score and a ≥ 2 point increase in Clinical Global Impressions-Severity rating relative to visit 3R. Endpoint was the last on-treatment, post-baseline visit of the randomized-withdrawal period (V4R–V9R) with a non-missing assessment

Quality of Life in the LDX relapse prevention studymean T-scores at baseline and endpoint of both periods

30.2 38.9 39.6

32.3 44.1 45.8

36.8 40.5 42.0

35.5 40.3 41.9

44.5 49.4 51.0

41.2 35.3

46.8 41.3

42.6 40.2

43.3 39.3

51.1 48.5

40.1

47.5

43.3

44.9

51.1

LDX (n = 76)

EndpointBaseline EndpointBaseline EndpointBaseline

LDX (n = 262)

Open label (≤ 26 weeks) Randomized withdrawal (6 weeks)50

40

30

Achievement

Risk Avoidance

Resilience

Satisfaction

Comfort

Placebo (n = 77)

The cognitive function of children and adolescents with ADHD in a two-year open-label study of lisdexamfetamine dimesylate

Coghill, Banschewski, Bliss, Robertsone , Zuddas (in preparation)

Delayed Matching to Sample

Spacial working memory

N= 314 (6-17y); LDX 51.1 mg/day (+14.3)

(Stop Signal Task [SST]& Reaction Time[RTI])

Genes & Environment

Genes & Environment



Cognition


Cognition




Traditional view of causal pathway to ADHD



CognitionCognition

SymptomsSymptoms


Alternative view of causal pathway to ADHD

Genes & Environment

Genes & Environment



Cognition


Cognition




Predictions arising from the traditional view of causal pathway to ADHD

If cognition and symptoms are causally linked in a linear manner it would expect that:

Genes & Environment

Genes & Environment



Cognition


Cognition





If cognition and symptoms are causally linked in a linear manner we would expect that:

When a treatment improves cognition it will also reduce symptoms When a treatment improves cognition it will also reduce symptoms

Genes & Environment

Genes & Environment



Cognition


Cognition






When a treatment improves cognition it will also reduce symptoms

When a treatment reduces symptoms it will also improve cognition



Genes & Environment

Genes & Environment



Cognition


Cognition








If symptoms decline over time, this would be associated with a similar improvement in cognition



If symptoms decline over time, this would be associated with a similar improvement in cognition



CognitionCognition SymptomsSymptoms

Environmental Factors

Medications

REDUCES

IMPROVES (some aspects of) X

Cognitive training

X



CognitionCognition

SymptomsSymptoms


Clinical Implications

The core symptoms of ADHD – as defined in the diagnostic systems-may not be a full description of what it means to have ADHD



CognitionCognition

SymptomsSymptoms



Treatments that reduce core ADHD symptoms may not also improve cognition and there may be residual ADHD related impairments.



CognitionCognition

SymptomsSymptoms




Treatments that improve cognitive aspects of ADHD may not also improve core ADHD symptoms (but may reduce impairment).



CognitionCognition

SymptomsSymptoms




Treatments that improve cognitive aspects of ADHD may not also improve core ADHD symptoms (but may reduce impairment).

As a consequence both treatments may be required.

Take home message


Executive dysfunction do NOT always explain ADHD symptoms and impairment

Neuro-economic models (dysfunction of executive, default, reward and time perception systems) may be more useful to explain ADHD psychopathology

Treatments that specifically reduce core ADHD symptoms or only improve cognitive aspects of ADHD, may not be effective to completely normalize ADHD-related impairment

Both symptoms and cognition treatment approaches may be required

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Trattamenti dell’ADHD bambino - EURAC research dell’ADHDnel bambino ... affects computation in...

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