psychological treatment for adhd can they be made to work? · blue games –inhibitory ... •...
TRANSCRIPT
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Psychological treatment for ADHDCan they be made to work?
Edmund Sonuga-Barke
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• Do they control core ADHD symptoms?
• Do parents think things have improved?
• Do they reduce other common comorbidities
• Do they improve everyday functioning?
• Do they change parent’s attitudes/behaviours to child?
• Do they promote parental wellbeing?
• Do they strengthen family functioning?
• Do they increase QoL in the long run?
DO NON-PHARMA ADHD TREATMENTS WORK? DEPENDS WHAT YOU MEAN! DEPENDS WHO YOU ASK!
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• Why is a stringent systematic assessment of non-pharma
interventions needed?
• EAGG methodology and strategy.
• Moving form targeting symptoms to underlying processes.
– Behavioural Interventions (Daley et al., 2014).
– Cognitive Training (Cortese et al., 2015).
– Neurofeedback (Cortese et al., 2016).
• Early intervention – a way forward?
RUNNING ORDER
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Sergeant (Netherlands: Chair); Banaschewski (Germany); Brandeis (Switzerland/Germany); Buitelaar (Netherlands); Coghill (UK); Cortese (US/Italy); Danckaerts (Belgium); Daley (UK); Dittman (Germany); Doepfner (Germany); Ferrin (UK/Spain); Fallisard (France); Hollis (UK); Konofal (France); Lecendreux (France); Rothenberger (Germany); Santosh (UK); Sayal (UK); Sonuga-Barke (UK/Belgium); Simonoff (UK); Stevenson (UK); Steinhausen (Switzerland/Denmark); Stringaris (UK); Thompson (UK); Van der Oord (Belgium); Wong (Hong Kong/UK); Zuddas (Italy); Santosh (UK); Holtman (Germany); Taylor (UK).
THE EUROPEAN ADHD GUIDELINES GROUPKNOWLEDGABLE AND PASSIONATE ABOUT ADHD TREATMENT
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• Medication - front-line treatment - effective but limited– normalization – rare– key functional outcomes untouched– long term effects - uncertain– side effects – frequent– resistance from parents and clinicians
– societal concern about the increasing prescribing rates.
• Effective non-pharmacological treatments are essential.
• EAGG produced treatment guidelines previously.
• Ten years ago decided to create non-pharma guidelines.
• We had loads of expertise - thought we knew the literature – easy then!
NEED FOR THE RECENT EAGG REVIEWS
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• What we found was that NPTs are recommended on the basis of systematic reviews and meta-analyses.
• Given this we initially considered a light touch – review of reviews - to generate our evidence.
• However – when we looked closely we found the existing reviews unsatisfactory in a number of ways.
On balance we did not feel the reviews were of sufficient quality to recommend NPT for ADHD.
Unfortunately some heavy lifting was needed.
A STRINGENT SYSTEMATIC REVIEW OF THE EVIDENCE WAS NEEDED
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EAGG METHODOLOGY
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• Randomised Controlled Trials with a suitable control arm.
• Peer reviewed
• ADHD diagnosis & outcome.
• 3 to 18 years
INCLUSION CRITERIA
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• The primary outcome was ADHD symptoms.
• The issue of blinding addressed by comparing two outcomes.
– MPROX – The ADHD assessment most proximal to the intervention setting – least likely to be blinded.
– P-BLIND – Only ADHD outcomes where the rater was likely to be unaware of treatment allocation – most likely to be blinded.
OUTCOMES
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PSYCHOLOGICAL INTERVENTIONS
a)Behavioural interventions
b)Neurofeedback
c) Cognitive training
DIETARY INTERVENTIONS
d) Restrictive elimination diets.
e) Artificial food colour exclusion.
f) Free fatty acid supplements.
g) Other supplements
NON-PHARMACOLOGICAL TREATMENTS REVIEWED
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MOVING FROM TARGETING ADHD SYMPTOMS TO UNDERLYING
PROCESSES
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• Based on reinforcement and social learning models.
• Delivered 1-2-1 or groups/at home or clinic - vary in duration/intensity.
• Trains parents and/or teachers in ways to modify their child’s behaviourby manipulating behavioural antecedence and consequences and modeling appropriate behaviours.
• Antecedents - Restructures child’s social and physical environment to ensure clear rules and expectations - communicated clearly and improvesparent-child relationship quality.
• Consequences – Positively reinforces appropriate behaviours and negatively reinforce alternatives to inappropriate behaviours.
• Can be implemented with social/organisational/academic skills training.
BEHAVIOURAL INTERVENTIONS
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BUT ARE POSITIVE EFFECTS OF BPT ON CORE ADHD SYMPTOMS EXPECTABLE?
BPT DEVELOPED FOR CONDUCT PROBLEMS ASSUMED TO EMERGE FROM COERCIVE PARENT-CHILD INTERACTIONS WHICH CAN BE
REMEDIED BY PARENTS’ ALTERED RESPONSE TO CHILDRENS’ BEHAVIOUR.
IS THIS A REASONABLE EXPECTATION FOR ADHD?
ARE THERE OTHER MORE EXPECTABLE POSITIVE BENEFITS OF BPT?
PARENTING BEHAVIOUR?
CHILD CONDUCT PROBLEMS?
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M-PROX
P-BLIND
ES = 0.02
ES = 0.40*
BEHAVIOURAL INTERVENTIONS
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M-PROX
P-BLIND
ES = 0.02
ES = 0.40*
BEHAVIOURAL INTERVENTIONS
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MOVING FROM TARGETING ADHD SYMPTOMS TO UNDERLYING
PROCESSES
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IF WE WANT TO TARGET ADHD SYMPTOMS DO WE NEED A RADICALLY
DIFFERENT APPROACH TO TREATMENT?
A TRANSLATIONAL MODEL HOLDS OUT THE PROMISE THAT PSYCHO-
THERAPEUTIC INNOVATION CAN BE BUILT ON SCIENTIFIC DISCOVERIES
ABOUT ADHD PATHOGENESIS.
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ORIGINATINGCAUSES
ADHD
NEURO-COGNITVE DEFICIT
COGNITIVE MEDIATORS OF CAUSAL PATHWAYS BECOME TARGETS FOR REMEDIATION
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ORIGINATINGCAUSES
ADHD
NEURO-COGNITVE DEFICIT
Training
COGNITIVE MEDIATORS OF CAUSAL PATHWAYS BECOME TARGETS FOR REMEDIATION
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ORIGINATINGCAUSES
ADHD
NEURO-COGNITVE DEFICIT
Training
COGNITIVE MEDIATORS OF CAUSAL PATHWAYS BECOME TARGETS FOR REMEDIATION
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ORIGINATINGCAUSES
ADHD
?
FOUNDATIONAL QUESTIONWHAT COGNITIVE DEFICITS MEDIATE ADHD CAUSAL PATHWAYS?
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ORIGINATINGCAUSES
ADHD
EXECUTIVEDYSFUNCTION
THE BARKLEY MODEL (REVISITED)
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inhibitionplanning
working memory
flexibility
ORIGINATINGCAUSES
ADHD
EXECUTIVEDYSFUNCTION
THE BARKLEY MODEL (REVISITED)
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“SCALPEL”
OR
“SHOTGUN”
FROM STRATEGY TO TACTICSRESPONDING TO THE NEUROPSYCHOLOGICAL IMPAIRMENT
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THE WORKING MEMORY TRAINING“SCALPEL”
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“A mental workbench” (Klingberg, 2009)“Dynamic brain process that helps us create and maintaininternal
representations” (Tannock, 2010)
Baddeley and Hitch Goldman-Rakic
WORKING MEMORY TRAINING FOR ADHD – A PRECISION APPROACH TO COGNITIVE TRAINING
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THE PIONEERING WORK BY TORKEL KLINGBERG AND HIS TEAM AT THE KAROLINSKA
ROBO MEMORY BE COGMED IS THE MOST WIDELY USED AND THOROUGHLY EVALUATED COGNITIVE TRAINING APPROACH
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Christos Constantinidis & Torkel KlingbergNature Reviews Neuroscience 17, 438–449 (2016)
IT CHANGES THE BRAIN
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THE MULTI-SYSTEMS TRAINING“SHOTGUN”
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N=14 N=15 N=8
* *
*
*
**
**
N=19 N=6 N=4
*
THE WORKS OF BRAIN: A GAMIFIED MULTI- PROCESS TRAINING
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WORKING MEMORY TRAINING
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INHIBITION TRAINING
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Rationale: Patients can self regulate brain activity to alter aberrant patterns using reinforcement procedures.Intervention: EEG measures of interest are converted into visual or acoustic signals and automatically fedback in real time to the patient using computers.
Two general approaches.
(i) EEG frequency band training - alter the balance between slow and fast EEG.
(ii) Slow cortical potentials training - regulates cortical excitation thresholds by focusing on activity elicited by external cues (so called evoked potentials).
NEUROFEEDBACK
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pos.
neg.
NORMALISATION OF EVENT-RELATED POTENTIALS
Heinrich et al. Biol Psychiatr 2004
attentional dysfunction
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Heinrich et al. Biol Psychiatr 2004
training gain
NORMALISATION OF EVENT-RELATED POTENTIALS
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M-PROX
P-BLIND
ES = 0.24
ES = 0.64*-3 -2 -1 0 1 2 3
Overall
Johnstone 2012
Johnstone 2010
Steiner 2011
Klingberg 2005
Shalev 2007
Rabiner 2010
Favours controlFavours control Favours treatment
Standardised Mean Difference (SMD)IV, Random, 95%CI
d. Cognitive Training
Overall SMD (95% CI) = 0.64 (0.33,0.95)Test for overall effect: Z = 4.07, p = 0.0001
Heterogeneity: 2 = 6.91, df = 5, p= 0.23, I
2 = 28%
COGNITIVE TRAINING
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M-PROX
P-BLIND
ES = 0.59*
ES = 0.29
NEUROFEEDBACK
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“Better evidence for efficacy from blinded assessments is required for behavioral
interventions, neurofeedback, cognitive training, ….before they can be supported as
treatments for core ADHD symptoms.” (Sonuga-Barke et al., 2013).
INITIAL CONCLUSION
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UPDATES AND EXTENSIONS
BEHAVIOURAL INTERVENTIONS
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0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
ADHD CP SOCIAL SKILLS ACAD
MPROX PBLIND
N=7N=17 N=7N=13 N=7
**
**
**
CHILD OUTCOMES – SUMMARY)
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0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
ADHD CP SOCIAL SKILLS ACAD
MPROX PBLIND
N=7N=17 N=7N=13N=7 N=7
**
**
**
CHILD OUTCOMES – SUMMARY
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-0.1
0.1
0.3
0.5
0.7
0.9
1.1
1.3
1.5
MENTAL HEALTH SELF ESTEEM POSITIVE NEGATIVE
MPROX PBLIND
N=7
N=8
N=11N=7
**
* **
*
*
*
N=5 N=7
ADULT OUTCOMES – SUMMARY
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-0.1
0.1
0.3
0.5
0.7
0.9
1.1
1.3
1.5
MENTAL HEALTH SELF ESTEEM POSITIVE NEGATIVE
MPROX PBLIND
N=7
N=8
N=11N=7
**
* **
*
**
N=5 N=7
ADULT OUTCOMES – SUMMARY
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-0.1
0.1
0.3
0.5
0.7
0.9
1.1
1.3
1.5
BEHAVIOURAL COGNITIVE NEURO
INITIAL
UPDATED
N=15N=8
* *
*
**
EQUAL EFFECTS FOR ALL BUT LIKELY TO BE AFFECTED BY PARENTAL BIAS
INITIAL AND REVISED ESTIMATES (MPROX)
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-0.1
0.1
0.3
0.5
0.7
0.9
1.1
1.3
1.5
BEHAVIOURAL COGNITIVE NEURO
INITIAL
UPDATED
N=15N=8
* *
*
**
ALL SMALL EFFECTS ONLY COGNITIVE SIGNIFICANT (JUST)
INITIAL AND REVISED ESTIMATES (PBLIND)
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• Do they control core ADHD symptoms?
• Do parents think things have improved?
• Do they reduce other common comorbidities
• Do they improve everyday functioning?
• Do they change parent’s attitudes/behaviours to child?
• Do they promote parental wellbeing?
• Do they strengthen family functioning?
• Do they increase QoL in the long run?
DO NON-PHARMA ADHD TREATMENTS WORK? DEPENDS WHAT YOU MEAN! DEPENDS WHO YOU ASK!
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HOW CAN PSYCHOLOGICAL INTERVENTIONS BE IMPROVED?
WHAT DOES THE DEVELOPMENTAL PERSPECTIVE INDICATE?
WILL INTERVENING EARLY OPTIMISE BRAIN PLACTIVITY AND
INCREASE LONG TERM EFFECTS ON CORE DEFICITS?
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NASCENT
PRODROMEOR HIGH RISK
FULL
COMPLEX
ESCAL’TING
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NASCENT
PRODROMEOR HIGH RISK
FULL
COMPLEX
ESCAL’TING
IMPAIRMENT
IMPACT ON FAMILY & COMMUNITY
ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE
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NASCENT
PRODROMEOR HIGH RISK
FULL
COMPLEX
ESCAL’TING
IMPAIRMENT
IMPACT ON FAMILY & COMMUNITY
ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE
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IMPAIRMENT
IMPACT ON FAMILY & COMMUNITY
ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE
NASCENT
PRODROMEOR HIGH RISK
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Over time, ADHD becomes more difficult to treat –behavioural habits engrained - comorbidities develop.
Lesion studies, computational modelling, animal models and neuroimaging show neural plasticity is greater, early
in development
Prevention neuroscience idea - cognitive systems can be strengthened before disorder onset in individuals at high
risk so that liklihood of disorder, its severity and persistence is reduced.
IS PREVENTION BETTER THAN CURE?
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PREVENTION NEUROSCIENCEPROTOTYPE #1 - HALPERIN & HEALEY’S ENGAGE
• Principle – Incorporating cognitive training into every day parent-child interactions with optimise gains in preschool.
• Targets– Working Memory
– Attentional Control
– Motor Skills Development
– Pattern Recognition/Visuospatial Organization
– Inhibitory Control
– Emotional Control
• Parents serve as primary delivery mechanism
– Learn to engage in fun play with their children
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Green Games – Working Memory
1) Shopping2) What’s Under There?
3) Copy Me
4) Memory Game
5) Remember the Treasure
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Yellow Games – Visual-Spatial/Pattern Recognition and Organization
1) Blocks
2) Puzzles
3) Beads
4) Track It
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1) Freeze Dance
Blue Games – Inhibitory Control
2) Puppet Says
4) Taboo
3) Red Yellow Green
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Parent Report*
0
5
10
15
20
25
30
35
40
Baseline
Post-Tx
1-Month
3-Months
TEAMS(n=27)
Control(n=26)
Teacher Report*
0
5
10
15
20
25
30
35
40
Baselin
e
Post-Tx
1-Mont
h
3-Mont
hs
TEAMS(n=27)
Control(n=26)
*Main effects Time: p < .05
RESULTS – ADHD
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EVIDENCE NOT COMPELLING SHOULD WE GO YOUNGER
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• Principle – Sophisticated reflection-based eye-tracking technology allows the direct training of attention through gaze contingent interaction even at this age.
PREVENTION NEUROSCIENCEPROTOTYPE #2 – WASS’ GAZE CONTINGENT ATTENTION TRAINING FOR
INFANTS
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TASK – SUSTAINED ATTENTION
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Visit 1 Visits 2-4 Visit 5
42 typical 12-month-old infants attend 5 visits over 2 weeks:
Controls (ersatz training)N=21
Pre-testing batteryN=42
Post-testing batteryN=42
Attention control trainingN=21
Avg. 77 minutes’ training per participant.
Wass, Porayska-Pomsta & Johnson, 2011 – Current Biology
STUDY 1 - DESIGN
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Reversal learningVisual sustained attention
-Δsaccad
ic R
T (
ms)
Δlo
ok d
urati
on
(sec)
Δp
ro
p.
co
rr.
an
ticip
. lk
.
Initial rule learning
Task switching
* * *
Saccadic reaction time
STUDY 1 - RESULTS
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Birkbeck- Mark Johnson- Emily Jones- Simona Salomone- Tim Smith - Luke Mason
University of Southampton - Edmund Sonuga-Barke- Anna Hunt - Martin Ruddock
University of East London - Sam Wass
King’s College London - Patrick Bolton - Tony Charman- Andrew Pickles- Emily Robinson - Abigail Runicles
Our funders: MQ Transforming Mental Health and the Medical
Research Council
CAN THIS REDUCE THE RISK OF ADHD IN CHILDREN AT RISK FOR ADHD?INTERSTAARS
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Participants• Fifty 10 – 14 month old infants with a first degree family member with
ADHD; increased familial risk for ADHD.
Baseline LAB and HOME (10 to 14 months)
Intervention (N=25)
Control group (N=25)
1. Five training sessions
2. Mid post-test HOME
3. Four training sessions
4. Outcome HOME
Outcome & follow ups
Follow up data collected at 2 and 3 years of age
DESIGN
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SUMMARY
• Approaches that target symptoms such as PT are valuable in many ways – but probably don’t target core symptoms.
• More translational approaches such as NF and CT currently lack evidence.
• Approaches targeting multiple processes my be more effective.
• Taking a prevention science approach may improve matters.
•Game based naturalistic approaches with pre-schoolers so far have limited effects.
• Gaze controlled training in infancy seems to improve cognitive control in the short term.
• Further work is required to optimise the impact of these approaches to target core ADHD symptoms.