Advances in the assessment and treatment of ADHD in adults with ID
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1 Advances in the assessment and treatment of ADHD in adults with ID Dr Dimitrios Paschos MRCPSych Consultant Psychiatrist & Hon. Research Fellow Islington Learning Disabilities Partnership Adult ADHD Service, Camden & Islington NHS FT Institute of Psychiatry, King s College London
2 Aims Increase confidence in recognising ADHD across the range of ID Increase confidence in prescribing & monitoring stimulant medication
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4 Does ADHD exist?
5 Does ADHD co-exist with ID?
6 Still controversial? From medical colleagues: ADHD does not exist or Everyone has ADHD No one had ADHD when I was growing up He doesn t have ADHD he was able to concentrate well during the consultation (7 mins)
7 WHY DIAGNOSE ADHD? Common (3-4% of children & 1% of adults) Disabling (academic, occupational & social impairment) High risk of psychiatric co-morbidity Treatable USA: over 90% of adults with ADHD never diagnosed
8 DSM-IV Diagnostic Criteria A: 1) 6 out of 9 inattention items 2) 6 out of 9 hyperactivity / impulsivity items B: symptoms were present before age 7 years C: impairment present in two or more settings (e.g. at school [or work] and at home)
9 DSM-IV Diagnostic Criteria D: clear evidence of clinically significant impairment in social, academic, or occupational functioning E: symptoms do not occur exclusively during the course of: Autism Schizophrenia or other Psychotic Disorder Symptoms not better accounted for by Mood, Anxiety or Personality Disorder
10 Inattention symptoms Often.. 1. fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities 2. has difficulty sustaining attention in tasks or play activities 3. does not seem to listen when spoken to directly 4. does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions) 5. has difficulty organizing tasks and activities 6. avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework) 7. loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools) 8. easily distracted by extraneous stimuli 9. forgetful in daily activities
11 Hyperactivity symptoms Often 1. fidgets with hands or feet or squirms in seat 2. leaves seat in classroom or in other situations in which remaining seated is expected 3. runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness) 4. has difficulty playing or engaging in leisure activities quietly 5. is on the go or acts as if driven by a motor 6. talks excessively
12 Impulsivity symptoms Often 1. blurts out answers before questions have been completed 2. has difficulty awaiting turn 3. interrupts or intrudes on others (e.g., butts into conversations or games)
13 DSM-5 changes 5 instead of 6 symptoms in adults Age of onset changed to 11 years old ( from 7)
14 Validity of diagnostic construct Reliability for operationally defined ADHD well established Validity questioned because of : - Symptom overlap with other common mental disorders -Symptoms lie in a continuum in the general population -No natural boundary between affected and unaffected individuals
15 Validating criteria I Symptom clustering -consistent research finding for both subtypes Distinguishing symptoms -ADHD often precedes the development of conduct disorder- the reverse does not occur
16 Validating criteria I COMT gene Catechol-O-Methy Transferance gene (causing increased breakdown of dopamine) associated with antisocial behaviour in adolescents with ADHD (finding reported in 4 separate samples)
17 catechol-o-methyltransferase (COMT) polymorphism (Eisenberg, 1999) n=164 DSM IV criteria, Conners Teaching Rating Hyperactivity scale, Continuous Performance Test False Alarm scale impulsive-hyperactive type of ADHD associated with the high enzyme activity COMT val allele.
18 Validating criteria II Distinguishing ADHD from normal range of inattention, hyperactivity, impulsivity -Severity in comparison to norms -Non-fluctuating course -Risk for co-occuring disorders -Association with functional impairment
19 Cognitive models of ADHD Problems with state regulation (related to arousal and activation levels) Delay aversion Inhibitory deficits: poor executive functioning Mood / motivation dysregulation
20 Impairment in motivation functions (Barkley et al, 2008) Item ADHD % Clinical % Community % Can t get things done unless there is an imminent deadline Has trouble motivating self to start work Has difficulty doing work by its priority
21 Cognitive models of ADHD II Multivariate family and twin analyses found 2 cognitive factors accounting for most ADHD: -Reaction time and reaction time variability -Omission and commission errors in continued performance tasks
22 Intra-individual variability of ADHD impairments Transient but frequent lapses of attention Moment to moment variability in performance Most studies focused on differences in performance between individuals with ADHD and those without
23 Aetiology: genetic, environmental and neurobiological factors Association with wide range of measures Both environmental and genetic factors likely to play important role
24 Structural and functional neuroanatomy of ADHD reductions in volume in cerebrum and cerebellum activation of more diffuse areas than controls during the performance of cognitive tasks hypoactivation of the dorsal anterior cingulate cortex, the frontal cortex and the basal ganglia
25 Dorsal anterior midcingulate cortex Critical role in attention, novelty detection, response inhibition and motivation Most evidence of dysfunction in ADHD across all studies Embedded in both reward processing and attention network
26 Role of dopamine Role in attention, cognition and reward / learning SSRIs did not show the same symptom relief
27 Role of dopamine II Blocking of DAT by MPH correlates with symptom improvement
28 Environmental risks Diet Toxins: Lead, Mercury Pregnancy and delivery complications Fetal alcohol exposure Psychosocial adversity
29 EPIDEMIOLOGY Prevalence of ADHD in Adults 2.5 to 4.3% (Kessler et al, 2006) Male to female ratio 2:1-3:1 Prescription data (UK): discontinuation rates in young adults far in excess of what would be expected by remission rates (McCarty et al, 2009)
30 EPIDEMIOLOGY Kooij et al (2005) validity of adult ADHD in a population based sample (n=1815) of adults18-75 yrs Prevalence in adults: 1% (cut-off 6 Sx; and 2.5% cut-off 4 Sx)
31 Intelligence and ADHD IQ tests not comprehensive assessment of higher executive functions (Delis et al, 2007) Sample of 49 high IQ (>120) children with ADHD showed pattern of cognitive, psychiatric and behavioural features typical of children with average IQ and ADHD High IQ young adults with ADHD & impairments in working memory
32 Differences in the development of cortical thickness of children with ADHD and below median IQ ADHD versus matched controls De Zeewu et all, 2013 n=200 no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas
33 ADHD in adults with Mild / Borderline ID Maltezos, 2008 N= 48 LD-ADHD (IQ< 80) vs 221 ADHD non -LD (IQ>=80) LD group higher number of the current inattentive symptoms' ratings and higher scores for all items during childhood Non-LD group: most symptoms improved from childhood to adulthood LD Group: five components accounted 73.98% of the variance for informants' ratings
34 Genetic Syndrome / Behavioural Phenotype Fragile X syndrome Prader-Willi Syndrome Tuberous Sclerosis Complex mutation ADHD or hyperactivity / impulsivity traits Yes Full FMR1 mutation increases risk Yes Early onset Comorbidity more common in maternal uniparental disomy Yes Up to 50% Possibly higher frequency in mutation in TSC2 Ref Hatton et al, 2006; Hagerman et al, 2009 Whittington & Holland, 2010; Cassidy & Driscoll, 2009; O'Brien & Bevan, 2011 Holmes et al, 2007; O'Brien & Bevan, 2011; Jones et al, 1999; Northrup et al., 1999 & 2011 Williams syndrome Yes O'Brien & Bevan, 2011; Lo- Castro et al, p11.2 microdeletion Yes highly penetrant cause of ID may account for 1% of cases of ASD 22q11 deletion Yes Also strong association with schizophrenia Weiss et al, 2008; Ousley et al, 2007 Baker & Skuse, 2005; Horowitz et al, 2005; Harrison & Owen, 2003 Neurofibromatosis 1 Yes Lo-Castro et al, 2011 Klinefelter Syndrome Yes Lo-Castro et al, 2011
35 Psychopathology and cognition in children with 22q11.2 deletion (Niarchou et al, 2014)
36 Psychopathology and cognition in children with 22q11.2 deletion (Niarchou et al, 2014)
37 ADHD in boys with the fragile X permutation (Farzin et al, 2006) full mutation >200 CGG repeats in the FMR1 gene premutation ( CGG repeats) considered unaffected by FXS Conners' Global Index-Parent Version, IQ scores similar in all groups Group ADHD ASD Probands 93% 79% nonproband premutation 38% 8% sibling controls 13% 0%
38 ASSESSMENT: Principles History of childhood ADHD is essential Collateral history always necessary Continuous rather than episodic features (developmental disorder)
39 ASSESSMENT 1. Structured full psychiatric interview with focus on Family history Personal, developmental, educational, occupational, and social history Current ADHD symptoms Co morbid conditions / substance misuse 2. Neuropsychological evaluation
40 MSE during assessment for ADHD Restlessness and distractibility may not be seen Sensitivity of symptoms to stimulating or novel situations Patients can normalise behaviour for short periods of time
41 ASSESSMENT rating scales Variety of validated questionnaires (Connors, Barkley) to assess current symptoms, monitor response to treatment Scales for retrospective childhood diagnosis, side effects Semi-structured interview schedules
42 Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist (WHO, available free on the web)
43 Barkley Adult ADHD Rating Scale IV (BAARS-IV) Results Summary Section Raw Symptom Percentile Significance score count Inattention Markedly/severely symptomatic Hyperactivity th Moderately symptomatic Impulsivity Markedly/severely symptomatic Total ADHD Markedly/severely symptomatic Total ADHD: 99 + centile
44 DIVA (Kooji, available free on the web)
45 Children with ID and ADHD use of rating scales (Deb et al, 2008) Aim to find cut-off scores for the Conners Parent Rating Scales-Revised (CPRS-R) and the Conners Teacher Rating Scale-Revised (CTRS-R) CPRS-R total score of 42: sensitivity of 0.9 and specificity of 0.67 CTRS-R total score of 40: sensitivity of 0.69 and specificity of 0.67 CPRS-R scores may distinguish between children with ID with and without ADHD but not the CTRS-R scores Need to develop an ADHD screening instrument specifically for ID
46 Neuropsychology Assessment 1. General Intellectual Functioning WAIS 2. Attention a. Selective b. Divided c. Switching d. Sustained 3. Impulsivity 4. Executive Function
47 Neuropsychological characteristics of adults with comorbid ADHD and borderline/mild ID (Rose et al, 2009) ADHD and mild-borderline ID (N = 59), ADHD and normal intellectual functioning (N = 95) co morbid group had significantly lower scores Differences remained significant after covarying for level of intellectual functioning ADHD and ID group vulnerable to double deficit
48 Neuropsychological characteristics of adults with comorbid ADHD and borderline/mild ID (Rose et al, 2009)
49 What is QbTest? Simultaneously measures attention, impulsivity and motor activity Performance compared to an age and gender matched normative control group Data Management System
50 How is the test performed? QbTest combines a motion capturing camera with a Continuous Performance Test specifically designed for age groups 6-12 years years
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54 Psychometric testing
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57 CO-MORBIDITIES: Adults Anxiety disorders 50% Mood disorders, antisocial disorders, and alcohol/drug: substantial prevalence rates
58 ADHD and Epilepsy (children) Kaufmann et al, % of children with epilepsy have ADHD vs 3% to 7% Possible causes: common genetic propensity, noradrenergic system dysregulation, subclinical epileptiform discharges, seizures, antiepileptic drug effects Children with ADHD: higher than normal rate of electroencephalography abnormalities ( % vs. 3.5%) MPT equally efficient in children with isolated ADHD and in children with ADHD and epilepsy (70%-77%) Caution: reports of seizure aggravation in MPT-treated children with uncontrolled epilepsy have raised concern.
59 ADHD and criminality N= 25,656 Significant reduction of 32% in the criminality rate for men and 41% for women as compared with non-medication periods Lichtenstein et al, 2012
60 ADHD, BAD, BPD: similarities and differences (Handbook for ADHD in adults, UKAAN 2013) Similarities with ADHD Differences from ADHD Borderline Childhood or adolescent onset Chronic trait like course Impulsivity anger Impaired social relationships Mood instability Pervasive across situations Identity disturbance Recurrent suicidal behaviour Chronic feelings of emptiness Frantic efforts to avoid abandonment Bipolar Overactivity Pressured speech Impulsivity Depressive episodes Sleep problems Mood instability Short attention span Episodic course Elated mood Psychosis Often lacks insight
61 TREATMENT Psychosocial interventions Pharmacotherapy
62 PSYCHOSOCIAL INTERVENTIONS CBT Family /couple interventions ADHD coaching Self-help groups Anger management, skills development
63 ADHD medication Amphetamines promote release of dopamine and noradrenaline Methylphenidate inhibits reuptake of dopamine Atomoxetine inhibits reuptake of noradrenaline
64 Drug treatment of ADHD Part of a holistic treatment programme Before starting and every 6 months: pulse, blood pressure, weight Bloods and ECG Review need to continue treatment annually
65 Licensed medication for treatment of ADHD in children in the UK Stimulants Methylphenidate Short acting: Medikinet, Ritalin Long Acting: Concerta XL, Equasym XL, Medikinet XL Dexamphetamine Dexedrine Elvanse Non-stimulants Atomoxetine Strattera
66 Stimulants for adults with ADHD Jou et al, 2004 and ID Small open label study Aberrant Behaviour Checklist-Community Version (ABC-C) Clinical Global Impression scale Significant improvements in the hyperactivity and irritability subscales of the ABC-C Adverse events minimal
67 Methylphenidate in Children with ADHD (Williamson et al, 2014) With or Without LD 6-week, double-blind,randomized, placebocontrolled, crossover studies evaluating individually determined doses of OROS methylphenidate versus placebo (n=135) In children with ADHD with or without comorbid LD, behaviour and performance improved during treatment
68 Case A- treatment Bloods, ECG, BP, Pulse normal No other psychiatric problems No substance misuse Started on Methylphenidate 5mg bd, titrated up to 10mg tds Highly significant improvements in all core ADHD deficits, academic performance and self management
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73 Stimulants: Efficacy Children response rates 25-73% Reduced efficacy in adults 1) Lack of consistent diagnostic criteria 2) Inadequate dosage 3) Presence of comorbidity 4) Poorly developed outcome measures
74 Stimulants side effects Well tolerated in adults Common side effects: insomnia, edginess, diminished appetite, dysphoria, headache Usually remit spontaneously over time Effect on BP/HR usually minimal US 1999 to 2003: 25 deaths, 26 serious adverse events such as heart attack or stroke
75 ELVANSE (lisdexamfetamine Inactive pro-drug Slow release, long lasting effect Less potential for abuse dimesylate)
76 Non - stimulants Atomoxetine (Strattera) noradrenaline reuptake inhibitor (NRI) or adrenergic reuptake inhibitor (ARI)
77 Other pharmacological treatments MAOIs Alpha 2 agonists e.g. clonidine Beta blockers Venlafaxine Modafinil Zyban Not many controlled trials in adults
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