Developmental paediatrics and pharmacotherapy in ASD and ADHD

1. Paediatrics: Child development and
the use of psychoactive medications
in school age children
Dr Megan Yap
General Paediatrician and
Developmental & Behavioural
Paediatrician
• “Dr Megs – Paeds & Feeds”
at http://www.kids-
health.guru/
• Paeds in a Pod (North Lakes),
Ipswich Hospital
October 2019

2. What are we talking
about today?
• Child development & where it can go wrong
• The role of the general/developmental paediatrician
and pharmacist
• Quick look: Developmental red flags
• Attention Deficit Hyperactivity Disorder
• Autistic Spectrum Disorder
• What are these conditions and how do they
present?
• How do we treat these conditions (and what is
the evidence)?
• Legalities of prescribing and administering
medications in the school environment.
• How can pharmacists help these children and
families?

3. Domains of Development
= areas of development that are
relatively distinct
• Gross motor
• Fine motor
• Speech & Language
• Social
• Later on… cognition, executive
function

4. Characteristics of normal development in
childhood
• Skills get more complex
• Always move onward and
upward (never backwards)
• Sequence is similar, but rates
vary within a normal range

5. Development and where it can go wrong…
• What conditions are we talking about
here?
• Autistic Spectrum Disorder (ASD)
• Global developmental delay (GDD)
• Attention Deficit Hyperactivity Disorder (ADHD –
3 types)
• Intellectual Impairment/Disability (I.I. or I.D.)
• Oppositional Defiant Disorder (ODD); Conduct
Disorder
• Speech and Language Impairment (SLI) and other
disorders of speech
• Generalised Anxiety Disorder (GAD)

6. What is the role of the General Paediatrician?
• Rule out medical causes
• Understand the whole picture of the child
• Make a diagnosis if necessary
• Formulate a plan

7. Developmental Conditions of Childhood - investigations
What needs to be ruled out?
• Sleep disorders – eg obstructive sleep
apnoea, limit setting disorder
• Hearing/vision impairment
• Mental health issues; social stressors
• Medical issues

8. What is the role of the pharmacist?
• First port-of-call
• Early detection of potential
issues
• Recognition of the sick child
• Treatment of simple ailments
• Referral point for sicker children
and more complex problems

9. What can you advise parents to do PRIOR to their
appointment with a paediatrician?
• HEARING and VISION tests
• Pure tone audiometry
• Visual acuity (optometrist)
• See their GP, who might have a think about
• Tests for medical conditions
• Referral to a psychologist/occupational therapist
• Manage aggravating conditions like sleep disturbance, constipation, excessive
screen time etc

10. RED FLAGS : ANY AGE
= absolute indications for further assessment
• Strong parent (or teacher) concerns
• Significant delay in milestones in one or more domains
• Regression (significant loss of skills)

11. RED FLAGS :
ANY AGE
(cont.)
Asymmetry of
strength/
movement/
tone
High or low
tone
Any parental
concern
about vision
or hearing
Poor interaction
(eye contact,
shared enjoyment,
shared attention
such as pointing &
showing)

12. RED FLAGS : ANY AGE (cont.)
• Stuttering that impairs child’s
intelligibility or peer interaction
• Unusual behaviours
• Eg – repetitive/ obsessive
- self injury

13. Attention Deficit
Hyperactivity Disorder
• A condition of development that causes
children to have poor concentration and a
limited ability to control their impulses. It is
not an illness.
• Common; 3-5% of Australian children; Boys >
girls
• More common in certain medical conditions
• Genetics important
• Environmental factors

14. ADHD (cont’d)
ADHD affects children’s “executive
functions.”
“Having ADHD” is more than a child
being “hyper”
With appropriate therapy and
intervention, children with ADHD can
lead a completely normal life.

15. • Skills in executive functioning are a
product of age. That is, they improve
as a child gets older.
• ADHD cannot be diagnosed in very
young children.
• Poor attention and concentration
and hyperactivity in little children is
NORMAL!

16. What is Autistic
Spectrum
Disorder?
• DSM-4 vs DSM-5
• Associations/comorbidities
• ADHD
• Anxiety
• OCD
• Depression
• ID
• ODD/Conduct disorder

17. Management
Behavioural therapy (1st line in kids under
6-7 years)
• Aimed at
• Building parenting skills and improving parent-
child relationship
• Self regulation skills
• Help with functional problems
• Environmental modification and meeting sensory
needs
Medication (always in combination with
behavioural therapy)
• Controls the symptoms
• Creates a WINDOW of opportunity where we can
teach the child what we need to

18. Environmental modification
Lots of things can be done to support kids’ attention and
concentration (even if they don’t have a diagnosis!)
• http://www.kids-health.guru/helping-attention-and -
concentration/
• School:
• sitting the child towards the front of the classroom
• predictable routine and structure to the day; built in rest
breaks
• Home:
• Set up homework area properly: TV off, uncluttered desk, no
toys around
• Visual schedules
• Task list – broken down into manageable chunks etc etc

19. The use of
psychoactive
medications in
children at school

20. What is psychoactive medication?
• A substance that affects a
person’s mental state by altering
brain function resulting in
transient changes in behaviour,
perception, mood and
consciousness
• Can be used medicinally (what
we are talking about today)
• Or recreationally (eg alcohol,
tobacco etc)

21. Why do we
use
psychoactive
medication for
in school aged
children?
• Poor executive functioning – poor attention,
concentration, planning/organisation skills (ADHD)
• Violent, aggressive or self-injurious behaviour eg some
children with ASD
• Oppositional and defiant behaviour
• Mood disturbance and anxiety (eg depression,
generalised anxiety disorder)
• Children with specific learning impairments with poor
attention/concentration, anxiety etc
• Children with psychiatric conditions – eg BPAD,
schizophrenia, other psychotic illnesses
***Often we are trying to treat more than one
condition/symptom***

22. ASD/ADHD
• There is a lot of overlap! Common
co-morbidities
• ODD/conduct D/o
• Anxiety/depression
• Speech/language delay; ID
• SLD
• What symptoms are we treating
most commonly?
• Inattention
• Hyperactivity
• Poor executive functioning
• Violent/aggressive behavior
• Depression/anxiety
• Social difficulties
• Insomnia
• What medications do we use:
• Stimulants
• Non-stimulants (guanfacine,
atomoxetine etc)
• Atypical antipsychotics
• Antidepressants/anxiolytics
• What are the benefits?
• What are the risks?
• What is the evidence?

23. Oppositional and defiant
behaviour and/or
Violent/aggressive behaviour
• What conditions?
• ASD, ADHD, ODD
• past exposure to trauma/abuse
• personality disorders
• sometimes depression/anxiety
• What medications do we use –
• stimulants in kids with concomitant
ADHD
• other meds that might work -
anxiolytics/antidepressants,
antipsychotics,
guanfacine/clonidine

24. Executive dysfunction
• Stimulants: eg methylphenidate,
dexamphetamine,
lisdexamfetamine
• Non-stimulants:
• eg atomoxetine,
• clonidine, guanfacine: alpha-2
receptor agonists (GF alpha-2A
selective in PFC; Cl central non-
selective alpha-2)

25. Stimulants
• High quality evidence (Gorman & Pringsheim RCTs 40; n=2364; duration 2-16 weeks)
• Moderate – large effect size
• Side effects: minor
• The only group of medications with strong evidence in favour of use
• When pharmacotherapy is considered for disruptive/aggressive behaviour in kids who have ADHD – a stimulant should be used
FIRST
• Some patients respond better to one stimulant than another, so a trial of each should be attempted before trying a medication
of a different class
• Even if a trial of one has had little success, it is worthwhile to figure out if that trial was of adequate dose and duration; and if
not, consider trialling more rigorously.
• All need growth and BP monitoring
• It is worthwhile considering “drug holidays” on weekends and school holidays

26. Stimulants
• Benefits: improvements to attention and
concentration, organisational skills, memory,
task completion, compliance/concordance and
at times mood, irritability, anxiety, self-esteem;
reduction in violent/aggressive/oppositional
behaviours in some children
• Risks: side effects are common – appetite
suppression, insomnia, increase in BP and HR,
irritability and/or emotional lability,
aggression/violent behaviour in some children;
worsening of tic disorders, small but serious
increase in risk of precipitating psychotic illness
in susceptible children, risk of cardiac
complications in children with family history
certain cardiac conditions

27. Other medications
used for
oppositional/defiant
or
violent/aggressive
behaviour
What are the benefits?
Reduction in undesirable
behaviours, increased
productivity/output in work,
participation in activities, better
relationships/social harmony –
home and school, happier child
What are the risks?
Well this depends on which drug
you are talking about…
Stimulants – we’ve already
spoken about this

28. Atypical antipsychotics for aggressive behavioural
disorders.
Risperidone – most commonly used  SE:
weight gain/obesity, metabolic derangement (eg
hypercholesterolemia, hyperprolactinaemia),
sedation, increased risk in cardiovascular disease
• Good evidence for effect BUT effect may only last a
few months (most trials only go for 12 weeks)
• Dose creeps up until SE burden
• Plan for SHORT TERM use only (6-12 weeks)
If children do not respond to a stimulant +
risperidone, there is really little else further
evidenced in the literature wrt other options.

29. Other atypical antipsychotics
Not a lot of evidence for safety in children – a big risk
Aripiprazole – commonly used when responsive
to risperidone but weight gain is a problem
• Low to moderate evidence (3 RCTs all in ASD
kids; n=408; 8 weeks; age range 6-17 years)
• Moderate-large effect size
• Side effects: moderate
• There is evidence to support short term use for
irritability in ASD only
• Most common SE: sedation, drooling, tremor
• EPS-related SE and weight gain – no significant
difference between groups
• Short term trials only
Quetiapine – similar SE profile to risperidone,
less frequently used but utility in children who
develop EPSEs or hyperprolactinaemia on
risperidone
• Very low evidence (1 RCT; n=19; age 12-17
years)
• Large effect size
• Side effects: major
• Only one small trial which was poor quality
• Potentially bad side effects
• Probably best not to prescribe (at least until
there is better quality evidence).

30. Alpha-2 receptor agonists
• Clonidine (not new)
• Guanfacine (new-ish)
• Used for hyperactivity/impulsivity (not
effective for inattention), aggressive behaviour,
sleep disturbance/insomnia

31. Alpha-2
agonists
Guanfacine
• Moderate quality evidence (Gorman article 2 RCTs, n = 678;
8-9 weeks)
• Small to moderate effect size; Side effects: moderate
• Adjunctive or monotherapy
• Single agent - Minimal benefit/intolerant SE from stimulant
• Adjunctive - Meaningful effect from stimulant and tolerated
BUT still behavioural challenges remain or shoulder
symptoms, more selective (alpha-2A) so less sedation (and
effect tachyphylaxis)
• BUT both studies for guanfacine were funded by Shire (the
manufacturer) so need to consider publication bias
(Spielmans GI et al 2010)
• Consider family/child’s medication compliance – don’t start
in unreliable patient  rebound hypertension/tachycardia

32. Alpha-2
agonists
Clonidine
• Very low quality evidence (Gorman/ Pringsheim RCTs 6; n=545; duration 6-16
weeks)
• Small effect size
• Side effects: moderate
• Adjunctive or monotherapy
• Monotherapy: Stimulants have little benefit or cause intolerable side effects
• Adjunctive: Meaningful effect from stimulant and tolerated BUT significant
behavioural challenges remain or shoulder symptoms; is sedative, but effect
wears off after about 4 weeks.
**** Effect size is small and uncertain (even though clonidine is SO widely used)
• 95% CI range for effect size is almost 0 (no effect) to 0.51 (moderate
effect)
• Kids need to be weaned off because abrupt cessation can cause rebound
hypertension and tachycardia
• Need to consider potential of child/family to comply with regular dosing!

33. Anxiety
People use this term for when they’re feeling
nervous or unduly worried – but anxiety is the
term for when the feeling persists even when
the trigger is removed.
It can occur as a single diagnosis, or
comorbidly with other conditions
Very often clouds the path to effective
treatment
• Social Phobia
• Specific Phobia
• Panic Disorder
• Anxiety Disorder Due to a General Medical Condition
• Substance Induced Anxiety Disorder
• Obsessive-Compulsive Disorder
• Acute Stress Disorder (much like PTSD, but lasts a month or
less)
• Posttraumatic Stress Disorder

34. Antidepressants/anxiolytics
• Fluoxetine, other SSRIs
• Cochrane systematic review show modest effects
of antidepressants compared to placebo
• Really only reasonable evidence in CHILDREN and
ADOLESCENTS for fluoxetine (and a little less for
fluvoxamine)
• Evidence for other SSRIs are similar in adults
• What are the benefits?
• Better mood, reduced anxiety, flow-on effects to
self-esteem, attention/concentration, school
output, academic achievement, social relationships
at home and school, quality of life, general health
• What are the risks?
• Side effects: nausea, vomiting, headache,
insomnia/somnolence, abdominal pain/upset,
diarrhoea… ? Increased risk of suicidality in
teenagers
• Risk of interactions when co-prescribed with
antipsychotics/stimulants

35. Other drugs used in behaviourally disordered
children…
• Sodium valproate - even though effect size estimated to potentially
be large, poor evidence and risk of major side effects means the value
of this is of uncertain significance
• Carbamazepine – don’t prescribe it; very poor evidence; it doesn’t
work
• Lithium - Don’t prescribe lithium; bad SE’s, results in 4 RCTs were
inconsistent so ??uncertain effect; needs blood monitoring, risk of
toxicity

36. Use of psychoactive medications in the school
environment
• Different schools have different rules
• On a general basis
• A letter to the school (addressed usually to the
school principal) that contains:
• Who the child is
• What medication they are on and what the dose is
• Which dose the school is being asked to help to
administer
• The author of the letter and qualifications
• **that the dose on box label may differ from the
current dose
• Labelled medication – child’s name, dose etc
• Medication must be kept at the school office
(not given to the child to self administer)
• If doses are to be given outside of school
hours (eg in the morning), parents are not
obliged to tell the school.

37. Helping paediatric patients and
their families in the pharmacy…
• Pharmacists are in the perfect
position to help
• Have a good understanding of
NORMAL development (or at
least have a tool to refer to eg
Denver developmental chart)
• Empathise and listen to them;
Acknowledge and validate
their concerns
• Know where to look for
information or who to ask if
you don’t know the answer
(no one knows everything!)
• Have a list of contact details of
reliable local professionals as a
resource for families
• Eg paediatricians, speech
pathology, OT, physio

38. Strategies to help support families with
children that have special needs…
• Think laterally around other things that the child might struggle
with and how you can help
• Eg feeding – eg feed thickener, various flow-rate teats
• Restricted eating – multivitamins
• Sleep disturbances
• Consider using a private counselling room/area if you have one
• Understand that these conditions are complex and that
pharmacological management of these conditions often aims to
treat more than one symptom
• Understand that a lot of parents would prefer not to medicate
their children, but weighing up risks and benefits, sometimes it is
better for them to medicate.
• Inform them, but don’t frighten them; keep a look out for
interactions
• Read (reliable sources of) information about these conditions
and their treatment
• Give patients and parents reliable evidence based information
(but avoid jargon!); give them information to take home
• Don’t judge – they may need to try several medications before
they find the right one

39. • Doctors are not infallible
• They may not know about
• Potential interactions
• Need for monitoring
• Dose adjustment
• Weaning
• Washout etc
• *Most* will appreciate sensible
advice from allied health
colleagues.

40. SUMMARY
Medications can be and are very useful tools to use at times in children for developmental conditions
They are NOT a “magic bullet,” they are NOT a “cure.”
They NEED to be used in combination with first line psychotherapy/behavioural intervention
Medicating children with challenging behaviours is… well, challenging.
•A lot of medications, even though commonly used don’t have much evidence supporting effect
There are risks (sometimes very significant ones) to be considered with all medications
There is a lot to consider with prescribing medications in children – eg individual traits, health factors,
risk factors, family ability to comply with regimen
Initiating medication in a child is a complex process of weighing up risks, benefits and also negotiating
a plan with the child and their parent

41. Where to get more information?
• Dr Megs – Paeds & Feeds blog
• http://www.kids-health.guru/
• Paeds in a Pod website
• https://www.paedsinapod.com.au/
• Royal Children’s Hospital (Melbourne) website
• https://www.rch.org.au/home/
• Raising Children Network
• http://raisingchildren.net.au/

42. References
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network meta-analysis. J Child Adolesc Psychopharmacol. 2019; 29(3):168-180.
2. Gorman DA, Gardner DM, Murphy AL et al. Canadian guidelines on pharmacotherapy for disruptive and aggressive behaviour
in children and adolescents with Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, or Conduct Disorder.
Can J Psychiatry. 2015;60(2):62-76
3. Pringsheim T, Hirsch L, Gardner D et al. Th pharmacological management of oppositional behaviour, conduct problems and
aggression in children and adolescents with Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, or Conduct
Disorder: A systematic review and meta-analysis. Part 1: Psychostimulants, alpha-2 agonists, and atomoxetine. Can J
Psychiatry. 2015 Feb;60(2):42-51.
4. Treuer T, Gau SS, Mendez L et al. A systematic review of combination therapy with stimulants and atomoxetine for attention
deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability. J Child
Adoles Psychopharmacol. 2013;23(3):179-193.
5. Spielmans G, Parry PI. From evidence-based medicine to marketing-based medicine: evidence from internal industry
documents. J Bioeth Inq. 2010;7(1):13-29.
6. Geyskes GG, Boer P, Dorhour Mees EJ. Clonidine withdrawal. Mechanism and frequency of rebound hypertension. Br J Clin
Pharmacol. 1979;7(1):55-62.
7. Reyes M, Buitelaar J, Toren P et al. A randomized, double-blind, placebo-controlled study of risperidone maintenance
treatment in children and adolescents with disruptive behaviour disorders. Am J Psychiatry. 2006;163(3):402-410.