Working with difficult children: Recent advances in ADHD

1. Working with difficult children: Recent advances in ADHD Eric Taylor King’s College London Institute of Psychiatry There are many ways in which children can be ‘difficult’: ADHD is just one. Behaviour is dysregulated : inattention, executive dysfunction, altered response to reward, poor time perception, and response disorganisation can all be involved. Assessment can guide education, help counselling, and lead to treating ADHD.

2. Lessons from research • It’s not their fault • Psychological treatments work • Medicines help the worst affected • Increasing range of medicines

3. More ‘diagnoses’ for child troubles Born mad or made bad? Crime and the child BBC to apologise for child drug program

4. Genetic influences 80%; Frontal, striatal, cerebellar parts of brain are small Same structures underactivate Psychological deficits Great differences over time Great differences in prevalence between countries Emotional & behavioural problems Performance variable Conflicts in understanding ADHD* Persistent and pervasive abnormalities in : Attention (distractible, forgetful, disorganised); Activity (restless, fidgety) and Impulsiveness (acting without thinking)

5. Where does ADHD come from?Twin studies show high heritability DZ MZ Twin correlations Median heritability (13 studies) 0.82 (0.52-0.98)

6. Search for high-risk alleles 7 (vs 2-5 or 8) copies of 48 bp VNTR on 11p.15.5 • DRD4 • metaanalysis p< .00000001 • Odds ratio (averaged): 1.32 • DAT1 • metaanalysis p<.0001 • Odds ratio (averaged): 1.13 9 vs 10 copies of 40 bp VNTR on 5p15.3 8 candidate genes well established to be associated with ADHD: mostly affecting dopamine or serotonin neurotransmission

7. Geographical variations in the number of repeats of the variable 48-bp sequence in DRD4 Chang et al

8. Genome scan identifies a spot on Chr 16: Cadherin 13 • Cadherins mediate cell adhesion and play a fundamental role in normal development. They participate in the maintenance of proper cell-cell contacts • CDH13 also implicated in substance misuse: Nicotine dependence Substance dependence • Plays a role in cell adhesion, cell-cell contacts and cell-migration

9. What is inherited? • Not ADHD: genetic influences on continuum* • Not a unitary trait: influences vary with context • Dispositions to react: • gene-environment interactions and correlations • early physical environmental associations • parenting influences on development • MAOA multiplies effects of violence, DRD4.7/DAT10 of smoking *(with possible exception at highest level of severity & possible latent classes)

10. Probable environmental associations Pregnancy • nicotine, alcohol, anticonvulsants, cocaine • lead, mercury; thyroid, immune rejection • stress; infections; toxaemia;APH Perinatal • low birth weight, O.C.s, perinatal care, [season of birth] Infancy • attachment problems, neglect, injury • socioeconomic adversity, nutrition Childhood • Course influenced by exclusion, hostility, injury, school

12. But, if ADHD is so neurological, how come it varies so much in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

13. Prevalence of disorder ADHD /1000 Real prevalence Administrative prevalence from local surveys; HKD in approx 105,000 nationally

14. Prevalence of disorder Same survey method in Hong Kong and East London

15. Is it a Social Problem? • Does society determine the presence of ADHD? • No, shared environment plays little part • Does society alter the rate? • Only small differences between societies • Little increase over time • Does society determine what is recognised? • Yes, substantial cultural differences

16. Is it a Treatable Problem? Patterson - OSLC

17. 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

18. Specific treatments • Psychological therapies:Parent training, behaviour mod, social skills • Licensed drugs:Methylphenidate, dexamfetamine, atomoxetine • Unlicensed drugs:Trial evidence:pemoline, imipramine, clonidine, bupropion, “Adderall”, modafinil, guanfacineAnecdotal: moclobemide, risperidone, sertraline • Diet: eliminations and supplements Include non-specific interventions - education, support, advice

19. A range of presentations: Xavier Xavier, aged 11, has been out of the control of his parents after an episode of meningoencephalitis at age 4. He is dangerously aggressive to his sister and younger brother and has been excluded from a special unit at school. He sets fires, steals from shops, and puffs cannabis with a group of older boys. He can’t concentrate in class, is very forgetful and disorganised; and teachers have believed that this comes from a chaotic home background.

20. A complex disorder, multiply caused Not just bad parents: Medication of child reduces parental EE • Not just complications: • In never-medicated adults: • Recent findings of low dopamine and DAT • Recent findings of persisting hypoactivation Not just genetic: The Environmental Risk Longitudinal Twin Study interviewed the mothers of 565 five-year-old monozygotic (MZ) twin pairs : the twin receiving more maternal negativity and less warmth had more antisocial behavior problems. (Moffitt et al 2008)

21. A range of presentations: Matteo Matteo is regarded by his parents as a charming 8-year-old who has recovered from injury but is now encountering bullying. His teachers, however, refer him to the clinic with a very different story: he does not listen to them, he does not concentrate as he should, he has low academic self-esteem and big tempers when frustrated, he is inclined to lose his way, he is clumsy and his handwriting is terrible. He was popular when he started at school, but now is teased a great deal. His teachers are frustrated because in individual sessions he shows good understanding and creativeness.

22. A complex disorder, multiply caused Inattention creates an increasingly unstimulating environment

23. Effect sizes on ADHD scales

24. Psychological interventions

25. Principles of psychological treatment • Identify specific problems • Analyse contingencies • Enhance adult attending • Teach effective instruction • Token economy + response cost (frequent) or time-out + rapid novel rewards • Include self- management

26. A school-based trial Tymms & Merrill (2009) 86 schools & 2,584 pupils in randomised trial Year 2 behaviour in schools receiving an Information Booklet was improved (ES = 0.26) Pupil attitudes to school and reading were improved (ES = 0.17) No effect of screening programme. Cost of booklet £2.55 (similar booklet in Taylor E (ed) People with Hyperactivity. CDM 171; MacKeith Press)

27. 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

28. But do behavioural treatments work? Metaanalysis Pelham & Fabiano (2008) review: Behavioural parent training Behavioural classroom management Intensive intervention in recreational settings Journal of Clinical Child and Adolescent Psychiatry 37 184

29. NICE approach: Systematic literature review

30. Cost-effectiveness calculation Sensitivity analyses for differing assumptions

31. 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.

32. 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

33. Neurofeedback trials meta-analysis

34. Month 36 0 14 24 10-m Follow-up Phase 22-m Follow-up Phase 14-m Treatment Phase R A N D O M A S S I G N M E N T MedMgt 144 Subjects Recruitment Screening Diagnosis Beh 144 Subjects 579 Subjects 7 to 9 yrs old ADHD-Combined Comb 145 Subjects CC 146 Subjects End of Treatment (14 m) First Follow-up (24 m) Second Follow-up (36 m) Early Treatment (3 m) Mid- Treatment (9 m) Baseline Pre-Baseline Observation 2 LNCG Group Observation 1 LNCG Group Assessment Points

35. Comparing Therapies:Conclusions from MTA Study • Medication is more powerful than behavioural treatment at 14 months • Research treatment better than routine • Many advantages in adding medicationto behavioural treatment; few in adding behavioural treatment to medication

36. Comparing therapies:MTA Timeline 8 Years 6 Years 24 Mos, 9-12 yrs 36 Mos, 10-14 yrs 14 Mos, 8-12 yrs Baseline, 7-9.9 yrs 10 Years Study Treatments 36 Month Findings on Substance Use Molina et al Randomisation ends

37. Jensen et al, 2007Intent-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

38. Equifinality of Interventions: How Should Clinical Services React? • Results underestimate treatment effects? • Treatments lack long-term benefit? • Extra benefits of intensive therapy fade? • Self-selection makes good outcomes

39. Subtyping ANXIETY / DEPRESSION IMP 1/4 SCHOOL HOME HKD HYP 3/5 INAT 6/9 IMPAIRMENT

40. ADHD versus HKD ANXIETY / DEPRESSION IMP 1/4 SCHOOL HOME HKD HYP 3/5 INAT 6/9 IMPAIRMENT

41. SNAP Hyperactivity-Impulsivity (Parent)

42. SNAP Hyperactivity-Impulsivity (Parent)

43. SSRS Total Social Skills (Parent)

44. Economic modelling Continue £ QoL Methylphenidate Parent training Methylphenidate Parent training Continue

45. Severe cases Continue Methylphenidate Parent training Methylphenidate Relative effect of medication to behavioural interventions greater in hyperkinetic subtype Parent training Continue

46. Treatment decisions • Severe, pervasive, disabling? • Problems at home? • Problems at school? • Persistent after treatment? • Comorbid problems? Home CBT ? Liaison + self-instruction Medication

47. 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

48. Drugs or behaviour therapy?Conclusions so far • Both are effective • Both are cost-effective • Medication hazards: • Growth suppression (manageable) • Hypertension (avoidable with monitoring) • Unknown risks to CVS • ADHD is heterogeneous in severity and course

49. 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?

50. Perhaps teaching cognitive control is hard because there are many routes into impaired control/ impulsiveness