Back to Basics
Review of ADHD and
Autism Spectrum
Disorders
Dhiraj Aggarwal, MD, FRCP (C )
Child and Youth Psychiatrist, CHEO
Assistant Professor, University of Ottawa
daggarwal@cheo.on.ca
April 9th , 2015
Disclosures
• No affiliations to disclose
Autism Spectrum Disorders
Outline
• Diagnosis
• Epidemiology
• Etiology
• Assessment
• Treatment
–Non medication treatments
–Medication treatments
Back to Basics – Dr. D. Aggarwal
ASD – Diagnostic Criteria DSM 5
A. Persistent deficits in social communication and social
interaction across multiple contexts, as manifested by
the following, currently or by history:
1. Deficits in social-emotional reciprocity, ranging, for
example,
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from abnormal social approach and failure of
normal back-and-forth conversation;
to reduced sharing of interests, emotions, or affect;
to failure to initiate or respond to social interactions.
ASD – Diagnostic Criteria
2. Deficits in nonverbal communicative behaviors
used for social interaction, ranging, for example,
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from poorly integrated verbal and nonverbal
communication;
to abnormalities in eye contact and body
language or deficits in understanding and use of
gestures:
to a total lack of facial expressions and nonverbal
communication.
ASD – Diagnostic Criteria
3. Deficits in developing, maintaining, and
understanding relationships, ranging, for example,
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from difficulties adjusting behavior to suit various
social contexts;
to difficulties in sharing imaginative play or in
making friends;
to absence of interest in peers.
ASD – Diagnostic Criteria
B. Restricted, repetitive patterns of behavior, interests,
or activities, as manifested by at least 2/4 of the
following, currently or by history:
1. Stereotyped or repetitive motor movements, use
of objects, or speech (e.g., simple motor
stereotypies, lining up toys or flipping objects,
echolalia, idiosyncratic phrases).
ASD – Diagnostic Criteria
2. Insistence on sameness, inflexible adherence
to routines, or ritualized patterns of verbal or
nonverbal behavior (e.g., extreme distress at
small changes, difficulties with transitions, rigid
thinking patterns, greeting rituals, need to take
same route or eat same food every day).
ASD – Diagnostic Criteria
3. Highly restricted, fixated interests that are
abnormal in intensity or focus (e.g., strong
attachment to or preoccupation with unusual
objects, excessively circumscribed or
perseverative interests).
ASD – Diagnostic Criteria
4. Hyper or hyporeactivity to sensory input or
unusual interest in sensory aspects of the
environment (e.g., apparent indifference to
pain/temperature, adverse response to specific
sounds or textures, excessive smelling or
touching of objects, visual fascination with
lights or movement).
C. Symptoms must be present in the early
developmental period (but may not become fully
manifest until social demands exceed limited
capacities, or may be masked by learned strategies
in later life).
D. Symptoms cause clinically significant
impairment in social, occupational, or other
important areas of current functioning.
E. These disturbances are not better explained by
intellectual disability (intellectual developmental
disorder) or global developmental delay.
Etiology
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Genetic - increased risk in siblings and in twins
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Twin concordance, monozyg. 60% vs 5% dizygotic
ASDs tend to occur more often in people who have
certain genetic or chromosomal conditions. About
10% of children with autism are also identified as
having Down syndrome, fragile X syndrome,
tuberous sclerosis, and other genetic and
chromosomal disorders
Environmental, toxins, gastrointestinal, immunological
factors inconclusive
Unproved Theories
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Vaccines containing thimerosal are not
associated with autism.
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No association between MMR vaccine and
autism
Consider Evaluation if by:
• 9m:
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no back-and-forth sharing of sounds, smiles and
other facial expressions
12m: No babbling or gesturing (pointing, waving byebye)
16m: No single words
24m: No spontaneous 2 word phrases (i.e. not just
echolalia or repeating someone else’s words)
Any age: any loss of any language or social skills
Consider Evaluation if •
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Abnormal eye contact
Aloofness
Not responding to one’s name
Not using gestures to point or show
Lack of interactive play
Lack of interest in other children
Evaluation
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History - Pregnancy, neonatal and developmental hx,
medical hx, family and psychosocial factors
Direct interaction and behavioural observations of child
Collateral of observations of child in social settings
Physical evaluation - identify dysmorphic features,
including neurological exam, head circumference, vision,
hearing
Psychological eval. - Cognitive testing, adaptive skills
Speech/language/communication assessment
OT evaluation
Medical Evaluation
• Standard of Care for all patients with ASD
• Chromosomal microarray analysis
• molecular DNA testing for Fragile-X
• Tests for selected patients with specific presentations
• Metabolic testing
• EEG if clinically observable seizures or history of
significant regression in social or communication
functioning.
• MRI
Shaefer Gen Med 2013; Miller AJHG 2010; Shen Peds 2010
Goals of treatment
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In order to optimize outcome, it is important to
screen/diagnose early and to initial intensive
behavioral therapy.
Promote functional conversational language.
Promote social interactions while mitigating
repetitive, self-stimulatory behaviors, tantrums,
aggression and self-injurious behaviors.
Unit 3 – Autism Spectrum Disorders – Dr. D. Aggarwal
Intervention
Applied Behavior Analysis (ABA):
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Uses the principles of operant conditioning to
teach specific social, communicative, and
behavioural skills to children with ASD. It
involves teaching new behaviours by explicit
reinforcement of these behaviours,
problem behaviours are often addressed by
carefully analyzing triggers or antecedents of the
problem behaviour in order to change the factors
in the environment that are contributing to the
problems behaviour.
Potential Target Symptom
Domains of Pharmacotherapy
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Hyperactivity and Inattention
Repetitive Behaviors
Irritability
RUPP Autism Network: Study of
MPH in Children with PDDs +
Hyperactivity
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Subjects: 72 children ( age 5-14 yr) with Autism
Asperger’s or PDD-NOS and significant ADHD
symptoms using DSM IV criteria
49% (35/72) responded to MPH (ES 0.3 to 0.5)
Hyperactivity and impulsive symptoms improved
more than inattentive symptoms
18% (13/72) dropped out due to AEs (decreased
appetite, insomnia, irritability (most common), dose
dependant.
RUPP Autism Network, Arch Gen Psychiatry 2005;62:1266-74
Treatment of Aggression and
Irritability
RUPP: Acute Risperidone Trial in Autism
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8 week, double-blind, parallel groups
101 subjects; Mean age 8.8 y (5-17 y)
Mean dose 2.1 mg/d, range 0.5-3.5 mg/d
59% decrease in Irritability score vs 14%
decrease in the placebo group
CGI-I scale differed by 64% percent for
children whose behaviour was much improved
or very much improved
Mean weight increase: Risperidone = 2.7 kg;
Placebo = 0.8 kg
RUPP Autism Network. N Engl J Med. 2002;347:314-321.
Placebo-Controlled, Fixed-Dose
Study of Aripiprazole in Autism
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8 week, double blind, placebo controlled
N =218 with autism and significant irritability
Age range 6-17yr, mean age 9.7yr
Fixed dosing trial, 5mg, 10mg, 15mg/day
All Aripiprazole doses better than placebo for
irritability
No significant difference between doses (5, 10, 15mg
vs placebo)
Mean weight gain: plc = 0.3kg, Aripiprazole
5mg/10mg =1.3kg; 15mg = 1.5 kg
Common side effects leading to discontinuation:
sedation, drooling, tremor, akathisia, EPS
Marcus, et al. J Am Acad Child Adolesc Psychiatry. 2009;48(11):1110-1119.
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Placebo-Controlled Study of
Aripiprazole in Autism
8 week, double-blind, placebo controlled
N = 98 with autism and significant irritability
Age range 6-17yr, mean age 9.3yr
Dose range 2 to 15mg/day (mean 8.5mg)
Aripiprazole significantly better than placebo for
irritability
Mean wt gain: placebo = 0.8kg; Aripiprazole
=2.0kg
Most common AEs: fatigue and somnolence
Owen, et al. Pediatrics. 2009;124(6):1533-1540.
Pharmacotherapy- Summary
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No treatment for core symptoms of social and
relationship problems in Autism
Risperidone1 (5-16 y) and aripiprazole2,3 (6-17 y) are
FDA-approved for irritability/aggression in children and
adolescents with autism
Stimulants effective in treating ADHD symptoms in
ASD patients
1RUPP Autism
Network. NEJM. 2002.
2Marcus, et al. JAACAP. 2009. 3Owen, et al. Pediatrics. 2009.
ADHD Outline
• Diagnosis
• Assessment
• Co-morbidity
• Epidemiology
• Etiology
• Natural History
• Treatment
Case
10 year old boy Joshua presents with difficulty
sitting still, distractibility and aggressive
behaviour.
Mother “The teacher thinks he has ADHD and
she told me to put him on Ritalin….I told the
school he is just an active boy and the school
should be able to manage him…..Dr. what do
you think is going on?”
Differential Diagnosis of ADHD
• Not every inattentive or disruptive child has
ADHD
• A child may be inattentive or act out because of:
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Learning problems, Mental Retardation
Mood (Depression or Bipolar)
Anxiety, including OCD
Autism Spectrum Disorder
Substance related disorder NOS
Sleep problems
Impaired hearing or vision
Personality Change Due to a GMC (ie head injury)
Age appropriate behaviours in active child
Understimulating environment (gifted child)APA, DSM-IV TR, 2000
DSM-5 Symptoms for ADHD
Inattention
Hyperactivity
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Doesn’t attend to details in
schoolwork
Difficulty sustaining attention
in tasks/play
Doesn’t listen
Doesn’t complete tasks
Difficulty organizing
Avoids tasks requiring focus
Loses things
Distractible
Forgetful
Fidgets
Leaves seat
Runs about
Doesn’t play quietly
“On the go”
Talks excessively
Impulsivity
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Blurts out answers
Doesn’t await turn
Interrupts or intrudes
ADHD Diagnostic Criteria (DSM-5)
• Inattentive symptoms (≥6/9), AND/OR hyperactiveimpulsive symptoms (≥6/9) (for age 17 and older at
least 5 symptoms are required)
• Several symptoms must have been present <12 y.o.
• Several symptoms must be present ≥2 settings
(home, school, work, friends, other activities)
• Clear interference in functioning (school, social,
family, work)
• Symptoms not better explained by another mental
health disorder or medical condition
What part of the assessment is the least helpful
in making the dx of ADHD in a 15year old teen?
a) Parent interview
b) Teen interview
c) Teen mental status
d) Rating scale completed by parent
e) Rating Scales completed by teacher
What part of the assessment is the most helpful
in making the dx of ADHD in a 15year old teen?
a) case conference with teachers and parents to
get a better understanding of the teens
behaviour at school
b) interview with parent about developmental
history and past academic history
c ) interview with the teen
d) observing the teen in class
e) rating scales completed by teacher and parent
Assessment in Children and Adolescents
• Parent interview including developmental
history
• Child/adolescent interview
• Information from teachers and other sources
• Rating Scales
-useful to support clinical evaluation and monitor progress,
but should not be used on their own to make a diagnosis
• Conners Rating Scale-Revised (Parent/Teacher)
• SNAP-IV Teacher/Parent Rating Scale (available at
www.caddra.ca)
Assessment (cont.)
• Medical evaluation:
– History and physical examination
– Hearing and vision tests
– Laboratory and imaging tests only if
indicated by the clinical evaluation
• Consider a psychoeducational evaluation,
including both cognitive and academic
testing, to assess for learning problems
Co-morbidity
• Children with ADHD have high rates of comorbid psychiatric disorders
• Almost 70% of children with ADHD had at
least one co-morbid condition
• Disorders that are frequently co-morbid with
ADHD:
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Learning disorders
Anxiety & depressive disorders
Oppositional defiant disorder & conduct disorder
Substance use disorders
Tic disorders
Pliszka et al., 2007; Spencer et al., 2007; Spencer et
al., 1999; MTA Cooperative Group, 1999
Father “How common is ADHD? What causes
ADHD? Will Joshua outgrow ADHD ? “
Prevalence of ADHD
• School age children: 6-9% (Wolraich et al., 1998; CDC,
2010; Ontario Child Health Study, 1989)
• Gender differences: 9.0% in boys (4-16 yrs
old) and 3.3% in girls (OCHS, 1989)
• Adult : 4.4% (NCS-R, 2006)
• ADHD accounts for 30-50 % of mental health
referrals (MTA Cooperative Group, 1999)
• ADHD presentations in children: (Polanczyk et al.,
2007)
– Combined (50-75%)
– Inattentive (20-40%)
– Hyperactive-impulsive (<5-15%)
Neurobiology of ADHD
• Genetics accounts for ~0.76 of the variance in ADHD
• Non-genetic factors > low birth weight/prematurity,
maternal smoking or drinking alcohol in pregnancy,
psychosocial adversity
• Parenting is not a cause of ADHD, but parenting
influences the outcome of ADHD
• Polygenic Disorder (many genes involved)
• Catecholamine dysfunction (Norepinephrine and
Dopamine)
Pharmacodynamics
• Methylphenidate:
–Blocks DA and NE transporters in the
presynaptic neuron, thus inhibiting reuptake
and resulting in increased synaptic
concentrations of these neurotransmitters
•Amphetamines:
–Stimulate release of DA and, to a lesser
extent, NE, from presynapticsites
–Have secondary effects on inhibiting DA
reuptake
Not just a Disorder of Executive functioning
(executive functioning)
/ supplementary motor cortex
(Stahl's Essential Psychopharmacology, 2008)
Father “I think my wife has ADHD. I made a
video to show you. what do you think ?”
Mother “ How do you treat ADHD? Are there
any side effects with medications? Are there
any long-term side effects of medications?
Behavioural Management vs.
Medication for ADHD
Non-Medication Interventions For Children
• Psychoeducation
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Explain the rationale for the diagnosis
Explain that ADHD is mainly a genetically and
neurobiological based disorder
Review the natural course of ADHD
Provide a sense of hope since ADHD is one of the most
treatable psychiatric conditions
• Behavioural Parent Management Training
• Behavioural School and Academic Intervention
AACAP ADHD Practice parameter. JAACAP. 2007
American Academy of Pediatrics. Pediatrics. 2011
Stimulants
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Methylphenidate
• Ritalin
• Biphentin
• Concerta
Duration of Action (hours)
4 (3-4)
8-10
12 (8-14)
Amphetamines
• Dexedrine
4 (3-6)
• Adderall XR
10-12
• Lisdexamfetamine (Vyvanse) 12-13
Stimulant Side Effects
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Initial insomnia
Decreased appetite, weight loss
Small increases in HR and BP
Stomachaches
Headache
Thirst,
Palpitations
• Anxiety
• Social withdrawal, decreased spontaneity
• Increased activity, aggression, irritability,
dsyphoria
• Tics
• Risk of growth suppression
Current Recommendations
Before initiating a stimulant
• Personal history
– of cardiac symptoms including syncope, palpitations, chest
pain, shortness of breath or seizures during exercise
– of cardiac disease including a clinically significant murmur
(not functional)
• Family history
– of premature (sudden/unexpected) death in family
members <40 years old
– of cardiac history including hypertrophic cardiomyopathy,
clinically important arrhythmias including long QT
syndrome (LQTS), Marfan syndrome
(Hammerness et al., 2011)
Contraindications to Stimulants
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Advanced arteriosclerosis
Moderate to severe hypertension
Untreated hyperthyroidism
Glaucoma
Hypersensitivity to the drug
During treatment with MAO inhibitors, and for up to 14 days
after discontinuation (hypertensive crises may result)
• Pregnancy
• Stimulants are not contraindicated in individuals with seizure
disorders, autism spectrum disorders, or Tourette syndrome,
but their use should be cautious in these populations
Atomoxetine (non stimulant)
• Selective norepinephrine (NE) reuptake
inhibitor (NRI)
• 24 hour coverage, OD dosing
• Effect size =0.6 (stimulants effect size = 1)
• Small benefit for anxiety symptoms
Monitoring for Stimulants and Atomoxetine
• Height and weight on growth charts
• HR and BP at baseline, with dose changes
and periodically thereafter
• Use parent and teacher rating scales to
monitor response and side effects at
different doses
Guanfacine XR (Intuniv XR)
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selective alpha 2A-adrenergic receptor agonist
Similar to clonidine, but less sedation & hypotension
four doses (1, 2, 3 and 4mg), OD dosing
2nd line treatment: Health Canada approval for the
treatment of ADHD in children aged 6-12 with suboptimal response to psychostimulants either as
– an adjunctive therapy to psychostimulants
– monotherapy
2014 CADDRA Guidelines Medical Treatment of ADHD
1st line
Adderall XR
Biphentin
Concerta
Vyvanse
2nd line
Atomoxetine
Guanfacine XR *
Short Acting Stimulants
Dexedrine
Dexedrine spansules
Ritalin IR
Ritalin SR
3rd line
Off label
Imipramine
Modafinil
Bupropion
* Guanfacine 2nd line only for children 6-12yr
(CADDRA ,2014)
(CADDRA, 2011)
(CADDRA, 2011)
Are There Side Effects of Not
Treating?
Side effects of the
ADHD meds are well
know but are the
consequences of not
treating ADHD as
well appreciated?
Domains of Impairment
Academic/
Occupational
Low selfesteem
Poor
Health/Injury
Impairments
Relationships
Traffic Violations and
Motor Vehicle Accidents
Smoking and
Substance
Abuse
Risky Sexual
Behaviour
Legal
difficulties
Questions ?