ADHD: clinical neurosciences by 7yZo450h


									      Psychological treatments in
                             Behaviour therapy
                             Cognitive therapies
                         Counselling about medication

          Eric Taylor:     King’s College London Institute of Psychiatry
No competing interests; acknowledgements to NICE Guidelines Development Group
What is it like to have ADHD?
   “My thoughts are in a muddle”
     (usually   only after treatment shows the difference)
   “I get into trouble a lot, I don’t know why”
   “Other kids pick on me”
   “Ive got a bad temper”, “I cant concentrate”, “Ive
    got ADHD”
      (usually repeating what they have been told)
What do patients ask for?
 Understanding by others
 Knowledge of future
 Stop the bullying
 Appreciation of the positive
 Time to talk with doctor
Which one is most similar?
Which one is most similar?

   1      2      3

   4      5      6
Which one is most similar?
Choosing the immediate reward

        30 sec
Choosing the immediate reward

  ?                   ?
        30 sec
    1p   1p   1p

?   ?     ?
    1p   1p   1p

?   ?     ?

Post - reward delay
        1p                     1p
             30 sec
  ?                   ?

Education should be widespread
   Children
   Parents
   Grandparents
   Siblings
   Classmates
   Teachers
   And increasingly for adult patients …
          Spouses, partners, employers
Key messages
 A real and potentially disabling condition
 Consider as a chronic disorder
 Families, peers and teachers can help ++
 Many affected people make good adult
 Medication helps but does not cure
Shaping the Environment
Longitudinal evidence from
Newham studies
 All 7-year-old boys (3,215) identified from
  school rolls and health records
 Parent & teacher Rutter scales for 2,462
 Stratified behaviorally into HA, Def, Inatt,
  Mixed & Control
 Random selection of 50 in each group
 Detailed interviews & tests: 91%compliance

            Taylor, Sandberg, Thorley, Giles (1991) Maudsley Monograph No. 33
 Outcome measures
 Parental interview ratings
 Psychiatric interview with youths
 Cognitive testing
 Home Office records of offending
 School records
 Case conference diagnosis

88% follow-up 10 years later; nonresponders similar to responders
   Hyperactivity & conduct disorder
         HA      Mixed     CD
Age 7

Age 17

         HA      Mixed     CD
   Hyperactivity & conduct disorder

Age 7
                 Hostile parental EE
                 Not part of a peer group

Age 17

         HA      Mixed              CD
   Hyperactivity & conduct disorder
Age 7

         HA     Mixed    CD
Age 17

Age 27
Basic handling framework for
parents – before specific therapy
   Appropriate expectations
   Positive attending to child
   Effective communication
         Obtain attention; simple instruction
         Listen; figure out meaning of outbursts

   Structuring the child’s day
   Rule-governed atmosphere
   Talking with teacher
Specific approaches: Behaviour Therapy
Principles of behavioural
 Identify specific problems
 Analyse contingencies; reward & response cost
    rather than extinction
 Enhance adult attending
 Teach effective instruction
 Token economy + response cost (frequent)
  or time-out + rapid novel rewards
 Include self- management
Principles of behavioural
 Identify specific problems
 Analyse contingencies; reward & response cost
    rather than extinction
 Enhance adult attending
 Teach effective instruction
 Token economy + response cost (frequent)
  or time-out + rapid novel rewards
 Include self- management
Interventions in the classroom
   Proximity to teacher
   Managed transitions
   Pacing & letting off energy
   Classroom aide
       operant conditioning
       peer advice
   Rule government
   Clarity of goal & speed of feedback
   Understanding disorder (eg projects)
   Monitoring medication
      Some common-sense procedures – avoiding distractors
      and short-chunk learning – don’t yet have trial evidence
Learning social skills in peer group
 Listen to others
 Join play gradually
 Learn the rules
      Avoid   intrusiveness and excessive demands
 Figure out why others react
 Control anger
 Learn how to refuse kindly
      Especially   drugs
             But do behavioural treatments
                  I. The MTA study

  Study                  36 Month Findings on Substance Use
Treatments                           Molina et al

          LNCG (n=289)
           added here
                                  0     14-m          14     10-m      24     22-m      36
                                      Treatment            Follow-up        Follow-up
                                        Phase                Phase            Phase

                    A                   MedMgt
                    N                  144 Subjects
  Recruitment       O
   Screening        M                      Beh
   Diagnosis                           144 Subjects
 579 Subjects       S
                    I                     Comb
 7 to 9 yrs old
                    G                  145 Subjects
                    E                      CC
                    N                  146 Subjects

 Pre-Baseline     Baseline     Early      Mid-     End of            First         Second
                             Treatment Treatment Treatment         Follow-up      Follow-up
                               (3 m)     (9 m)     (14 m)           (24 m)         (36 m)
                                                                Observation 1     Observation 2
                                                                LNCG Group        LNCG Group

                                  Assessment Points
Jensen et al, 2007
Intent-to-treat (ITT) Analysis
 MTA Group, 1999a,b

    MTA Group, 2004a,b

                         Randomized Clinical
                         Trial at 14-month
                         assessment: Transition
                         to Naturalistic Follow-up
                         at the 24-month & 36-
                         month Assessment
    Towards consensus in clinical practice
Stage             Example

Recommendations   “Seek underlying causes before prescribing”

Guidelines        “Assess learning difficulties, family history,
                  peer relations, stress history”

Protocols         “100% of referred cases are evaluated by child
                  psychiatrist giving individual interview”
               Towards clinical guidelines
Stage          Information     Source          Result
Review         Trial results   Expert Review   Draft of
                               Metaanalysis    recommendations

Critique       Clinical        Referee         Recommendations
               Literature      Expert panel

Modulation     Acceptability   Users
               Cost            Purchasers      Guidelines
               Subgroups       Field trial

Modification   Local factors   Providers
                               + purchasers    Protocols
Organisation of NICE process
   Professional team         Panel
   Systematic reviewers      Psychiatry
   Health economists         Paediatrics
   Secretariat               Primary care
   Implementers              Education
                              Users
                                     Commissioned project
                              Carers
Key recommendations from NICE
   ADHD should be recognised and referred
 Comprehensive specialist assessment; impairment req’d
   Trusts to set up lead group
   Adult services to be developed
   First choice usually group parent training
   Severe cases go straight to medication
   First choice medication usually MPH
   Shared care expected
Systematic literature review
  Table 5. Databases searched and inclusion/exclusion criteria for clinical evidence
  Electronic databases           CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO

  Date searched                  Database inception to 18.12.08

  Study design                   RCT

  Patient population             Children diagnosed with ADHD
  Interventions                  Any non-pharmacological intervention used to treat ADHD symptoms
                                 and/or associated behavioural problems

  Outcomes                       ADHD symptoms*; conduct problems*; social skills*; emotional
                                 outcomes*; self-efficacy*; reading; mathematics; leaving study early
                                 due to any reason, non-response to treatment.

  *Separate outcomes for teacher, parent, self, and independent ratings.
Marking and combining studies
Core ADHD symptoms at end of treatment (teacher-         SMD -0.25 (-0.56 to 0.07)
      rated)                                             Quality: High
                                                         K = 4, N = 163

Core ADHD symptoms at end of treatment (parent-          SMD -0.57 (-1.00 to -0.14)
      rated)                                             Quality: Moderate
                                                         K = 5, N = 288

Conduct at end of treatment (teacher-rated)              SMD -0.12 (-0.61 to 0.38)
                                                         Quality: Moderate
                                                         K = 3, N = 63

Conduct at end of treatment (parent-rated)               SMD -0.54 (-1.05 to -0.04)
                                                         Quality: Moderate
                                                         K = 5, N = 231
Social skills at end of treatment (teacher-rated)        SMD -0.40 (-1.33 to 0.54)
                                                         Quality: Moderate
                                                         K = 1, N = 18

Social skills at end of treatment (parent-rated)         SMD -0.59 (-1.80 to 0.61)
                                                         Quality: Low
                                                         K = 2, N = 138

Social skills at end of treatment (child-rated)          SMD -0.23 (-0.61 to 0.15)
                                                         Quality: High
                                                         K = 1, N = 120
Emotional outcomes at end of treatment (teacher-rated)   SMD -0.20 (-1.12 to 0.73)
                                                         Quality: Moderate
                                                         K = 1, N = 18

Emotional outcomes end of treatment (parent-rated)       SMD -0.36 (-0.73 to 0.01)
                                                         Quality: High
                                                         K = 2, N = 112

Self efficacy at end of treatment (child-rated)          SMD -0.03 (-0.48 to 0.42)
                                                         Quality: High
    Psychological interventions
      Type            Delivery             Costed as:
Parent training   Group             10 sessions

                  Individual        10 sessions

                  Group + child
Cognitive         Individual        n/a [no effect]

Educational       Class information Delivery to teacher

                  Screening         n/a
Modelling health economic costs
                                 the structure of the economic model
  Figure 3. Schematic diagram ofResponse
                                                  Booster sessions

                  Parent training

                                    No response
                                                  No treatment
  Children with
                                                  No treatment

                  No treatment

                                    No response
                                                  No treatment
Selecting studies with “response rate”
outcome measures (to allow QALY)

  Table 8. Characteristics of the studies examining parent-based therapies for children
  with ADHD included in the guideline systematic literature review
  Study             Intervention examined                                Mode      Medicatio
                                                                         of        n status

  BOR2002           Enhanced and standard positive parenting programme   Individ   None

  HOATH2002         Enhanced positive parenting programme                Group     Some
  PFIFFNER1997      Social skills training with parent generalisation    Group     Some

  SONUGA-           Parent training                                      Individ   None
  BARKE2001                                                              ual
Table 9. Input parameters utilised in the base-case
   economic analysis of parent training versus no
   treatment for children with ADHD
Input parameter                      valu       Source - comments
Response rates                       0.522      Meta-analysis of BOR2002,
Parent training                      0.206          HOATH2002, and
No treatment                                        SONUGA-BARKE2001;
                                                    analysis based on
Utility scores                       0.837      Coghill et al., 2004; scores based
Responder                            0.773          on EQ-5D; questionnaires
Non-responder                                       filled in by parents of
                                                    children with ADHD in the
Parent training cost                 £660       Curtis & Netten, 2006; clinical
10 x 1 hour group sessions with       £29            psychologist cost per hour:
      clinical psychologist          £689            £29; cost per hour of client
1 extra hour training and             £69            contact: £66; qualification
      preparation                     £99            costs excluded
Total intervention cost              £168
Total cost per family, assuming 10
      families in each group
3 x 0.5 hour individual booster
      sessions for responders
Total cost for responders over 1
Cost-effectiveness calculation

 Table 10. Cost-effectiveness of parent training versus no treatment in
 children with ADHD - results of the base-case analysis over 1 year

 Intervention   Total QALYs /   Total cost / child   ICER

                0.803           £168
                                                     Parent training versus no
                                                     treatment: £6,608/QALY
 No treatment   0.785           0

                Sensitivity analyses for differing assumptions
 Economic conclusion

According to this analysis, and after assuming an 80%
uptake of such programmes,
the group clinic-based programme resulted in a cost per
responder of £10,060 and £1,006 at a 5% and 50% success
(response) rate, respectively; and a cost per QALY of
£12,575 and £3,144 at a 5% and 20% improvement in
HRQoL, respectively.
Clinical conclusions

The results of the economic analysis indicate that
group-based parent training programmes (or CBT for
children of school age) are likely to be cost-effective for
children with ADHD, if the mode of delivery of such
programmes does not affect their clinical effectiveness.
Individual parent training is unlikely to be a cost-
effective option
Specific approaches: cognitive therapy

           Effective for coexistent anxiety/ depression
            For Core ADHD symptoms, little effect:
                         Learning to STOP AND THINK
                        Recognising and managing anger
                       Teaching others to be self-controlled
                               Tolerating waiting

  So far, trial evidence suggests no effect on core ADHD. What are we doing wrong?
Perhaps teaching cognitive control is
hard because there are many routes
into impaired control/ impulsiveness
         GONOGO                  STOP

 press      inhibit
 Selective inhibition of a     press       inhibit   ISI: 1.6s
 motor response/response     Withholding of a planned motor
 selection                   response


press            inhibit
       Successful inhibition in normal

Rubia et al., 1999, NeuroImage.
R (-unsuccessful)

           ADHD: 0

                                     C > ADHD

Rubia et al., AJP, 2004, in press.

Modification of Meiran Switch task: Cognitive flexibility.
Switching between two dimensions.
SWITCH (- repeat)
RIGHT           C        LEFT

              ADHD: 0
Entering adult life
 Counselling – what to expect?
 Learning coping skills
 Making autonomous decisions
 Becoming intelligent users of treatment
Stresses of growing up with ADHD

 Ideas of self
 Coping with treatment
 Biological determinism
 Stigma and incomprehension
 Different impact at different life stages
ADHD: Outcome for diagnosed children

                                           Percentage with ADHD

  % still showing disorder

                                  age 14      age 18    age 22

   Median values for all follow-up studies from childhood
          Types of Remission
   Syndromatic remission
      Loss    of full diagnostic status

   Symptomatic remission
      Loss    of subthreshold diagnostic status

   Functional remission
      Loss  of subthreshold diagnostic status with functional

Keck PE Jr, et al. Am J Psychiatry. 1998;155(5):646-652.
Age-Specific Prevalence of Remission:
                               90        Syndromatic
                               80        Symptomatic
      % Remitting Diagnosis

                               70        Functional
                                    <6   6-8   9-11    12-14   15-17   18-20
                                                Age (Years)

Keck PE Jr, et al. Am J Psychiatry. 1998;155(5):646-652.
Impulsiveness as a failure

     The charge of the light brigade: impulsiveness and
     inattention in Captain Nolan, rigidity in others
Impulsiveness as a strength

                      “That adventurer”
Impulsiveness as a mixture

                   Genius and failure
Changes in adolescence
   Brain maturing:
        Synaptic   cull, cerebellar growth, fibre tracts, frontal
   Endocrine:
        Mixed    effects of testosterone & early puberty
   Physical:
        Sexual   attractiveness & interest
   Cognitive:
        Abstract   conceptual; hypothetical probabilities
Entering adult life
   New demands                          New chances
       Study: self-regulated, more        Self-pacing
       Work: regularity,                  Choose  own niche
        submitting to rules,               Avoid hated situations?
        unreasonable people
                                           Find helpers
       Friends: more demanding
                                           Use skills
       Partners: sharing
       Drugs & alcohol                    Brain maturing
       Budgeting, negotiating
       Self-organisation
            Finding   things/ remembering appts/ budget/ neatness
       Timing
            On   time for work/meet deadlines/ pay bills
       Thinking
            Muddled/   Distracted/ “Whirling”/ Incomplete
       Impulse control
            Negotiating/   Using drugs/ Mood stability

Coping often by: prosthesis; delegation; “buddies”; job choice
 Forensic: vulnerable/witness/competence
 Employment; accident-prone; strengths
 Parenting problems affect the children
     What   influences operate?
       Antisocial: abusive/modelling/discipline
       Cognitive: unfocussed/impoverished

       Conative: reward history/predictability

       Physical: fetal/perinatal/nutritional/injury
Adherence and attitudes
   Tom is 15. Professional parents. White British.
   Mixed neuropsychiatric presentation:
     Presented at age 10 with history of impulsive overactivity
      throughout his life; asked to leave nursery; multiple
      suspensions from primary school and three changes of
      school (all mainstream) due to mother’s perception of school
      failing him
     Reading age then was 7; WISC IQ 106; noncompliant with
      tasks seen as difficult
     Increasingly unpopular; steals to give to other kids
     Violent to his younger sister, not otherwise

   Treated with Concerta (in spite of tics appearing); good
    response, maintained in mainstream with facilitator,
Problems now
 Age 14 increasing cannabis use; agreed to
  continue Concerta (54 mg daily) none the
  less; off medication at weekends and
  holidays; discussions in motivational
  interviewing format.
 Age 15 behaviour at school deteriorated.
  Concerta increased; clonidine added; not
  helpful; admitted not taking medicines
 Wont accept a self-monitored trial; “dunno”
  and “don’t like it” on his objections.
Patients taking stimulants                                   (General Practice Research Database)

                                                              Female   Male      Total


   Number of patients



                         50                                            36
                                                                                             20 25
                                               7                                                         13 19
                                                                  6                      5           6
                                   16              17                  18                    19      20 to 21
                                                                 Age, years
Common reasons for
   Forget
   Stigma
   Not real self
   Losing funny side
   Adverse effects
        Physical; sex; tension; feared brain damage
        Incompatible with misused substances

   Inconvenience
   Don’t need it
   Up to me
   No point
Attitudes of young people to

    Harpur (2006, PhD thesis Southampton)
         Predominantly  positive
         “Adherence” is complex – individually chosen
          regimes, often by parents (Singh, 2006, Am J Med
          Ethics: “authenticity”) – adherence to what?
    Ferrin (2007, MSc, London)
         Questionnaire from Childrens Health Beliefs model:
         locus of control, self-esteem, general beliefs on
         medicine, knowledge
                perceived threat and benefit
                doctor-patient relationship
Outcome and adherence
   Simpson et al BMJ 2006 333 15
     Metaanalysis: good adherence in about 50%;
      predicts good outcome, even for placebo.
      (“healthy adherer”)
   Charach et al J Amer Acad CAP 43 559
     Adherence to stimulants over 5 years predicts
      good outcome, is predicted by youth, severity
      of ADHD, no ODD
Attitudes of young people to

  Project commissioned from LSE (Singh)
  Qualitative interviewing
  Attitudes predominantly positive
  Negative aspects acknowledged
         Inconvenient

         Stigmatising for some
         Sleep/appetite problems

    Better for some activities, worse for others
What do patients ask for?
 Understanding by others
 Safe treatment
 Knowledge of future
 Stop the bullying
 Appreciation of the positive
 Time to talk with doctor

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