Post on 20-Apr-2022
Psychotropic medications for
childrenDr Brendan Belsham
Child and adolescent psychiatrist
www.drbelsham.com
Lund
beck
Janssen Novartis Shire Lilly Cipla Adcock Mylan
Speakers
honoraria xx x
Conferences x x x x x x x x
Advisory
boardsx x x
Disclosures
Pharma
plan
Ethical considerations
How do we know a treatment works?
How does the treatment work?
The synapse
Serotonin, Dopamine, Noradrenaline
Specific conditions and their treatment
Monitoring medication
How long to treat for?
Take-home messages
Outline
Ethical considerations
Consent
Children may consent to medical treatment from age 12 if competent to
do so (Children’s Act)
Assent
the agreement of someone not able to give legal consent to participate in
the activity
treatment of minor children requires the consent of the parent or legal
guardian and the assent of child, wherever possible
Children’s Act 38 of 2005 Section 9:
‘the child’s best interests are of paramount importance and must take
precedence over every other consideration’
Section 30:
The holders of parental responsibilities and rights enjoy a large measure
of autonomy
Each parent may exercise such responsibilities an rights without the other’s
consent, however:
Section 3:
Due consideration must be given to the wishes of the minor child, and to
the wishes of the other parents
Off label use of medications
The use of medication for an age-group for which it is not
registered
Several medications used in children ‘not recommended for use in
children under the age of 18’ (eg SSRI’s)
This does not mean that these medications are not evidence-based, as
reflected in various treatment guidelines
The use of medication for a condition for which it is not
registered:
Eg Risperidone in ADHD
Medication as part of a holistic plan
The ‘biopsychosocial’ approach (add spiritual)
Medication is not always required, and is usually only instituted
once more conservative measured have failed
The perils of medical reductionism
How do we know a treatment works?
The randomized, placebo-controlled treatment trial:
1. Collect a group of kids reliably diagnosed with the condition. The group must be large
enough to provide meaningful results.
2. Randomly split them into two groups
3. One group receives the tested treatment, the other (control group) takes fake pills. The
fake pills are the placebo, a ‘treatment’ which doesn’t contain the active ingredient but
is in other respects indistinguishable; it looks, tastes and feels the same, and is
administered in the same way
4. The placebo response is typically very high in children (30-60%), and many well-
designed trials have struggled to show that the tested treatment actually beats placebo
5. After a reasonable time period, say four weeks, I measure how each group has done
(using an accepted rating scale) and compare their progress
Clones and generics
Generic
Released on the market when the patent for the originator expires
Significantly more cost effective
Same active ingredient but different company, different manufacturing
plant, different bulking and filling agents, which can affect absorbtion,
hence may not be as effective
Clone
Released on the market to compete with the generic
Same company, same manufacturing plant, same bulking and filling agents
Priced in between originator and generic
Attention Deficit Hyperactivity
Disorder
A biological, brain condition causing developmentally
inappropriate impairments in concentration,
hyperactivity and impulsivity
Affects 5% of school-age children, and 4% of adults,
across all cultures
3:1 males to females (in childhood)
A chronic disorder with significant impairment and cost
to society across the life span
Stimulants
Immediate release MPH: Ritalin 10mg
Methylphenidate HCI Douglas
Long acting LA Ritalin (10, 20, 30, 40mg): 6-8 HRS
Extended release methylphenidate Concerta (oros-methylphenidate)
Neucon
Contramyl
10-12 HOURS
18, 27, 36, 54mg
4 HRS
DAT1
DRD4
Direction of transmission
Dopamine
X
Adverse effects Stomach aches
Headaches
Appetite suppression
Sleep disturbance
Tics (abnormal involuntary muscle movements)
Transient increase in pulse, blood pressure
Emotional effects
Anxiety
Subduing, social withdrawal
Depression, suicidal thinking
Psychosis
Long-term effects of stimulant
medications
Growth
Brain structure
Later substance abuse
Effects of stimulants on growth
Consensus is that stimulant treatment can slow
down the rate of growth
However:
As yet no relation shown to reductions in final adult height (Weiss
and Hechtman, 2003)
ADHD kids are shorter at baseline before starting medications (ADDUCE trial, 2016)
Drug holidays
May allow catch-up growth and weight gain
Brain structure and function
Structural MRI
Overall, studies suggest that over time, stimulant treatment is associated with a
normalisation/attenuation of the brain abnormalities associated with
unmedicated ADHD
White matter AND grey matter
Functional MRI
Stimulants enhance activation of prefrontal cortex during cognitive tasks (more
normal)Rubia 2014
Spencer 2013
‘Kiddie Cocaine’
ADHD is itself associated with an increased risk of substance
abuse
Poor impulse control
Academic underachievement
Low self-esteem
Comorbid anxiety, conduct disorder
Treating ADHD in no way aggravates the risk if later substance
abuse; if anything, it is protective
Substance abuse in unmedicated and medicated ADHD and control adolescents
(>15 years)
0
10
20
30
40
50
60
70
80
Unmedicated Medicated Control
Biederman, 1999
Atomoxetine (Strattera)
Blocks reuptake of noradrenaline at the synapse
Advantages:
Once daily dosing
Does not aggravate tic disorders
Does not aggravate anxiety; may improve it
Provides 24-hour cover, improving quality of life at home, in the early
mornings and around bedtime
Disadvantages:
Takes 4-6 weeks before improvement is evident (as opposed to days
with the stimulants)
Smaller effect size
Must use correct dose, 1.2-1.8mg/kg
Atomoxetine side-effects
Appetite suppression
Sleep disturbance or somnolence
Constipation
Mood effects especially irritability
Other evidence-based treatments
Alpha-2 agonists
Clonidine (Dixarit, Menograine)
Guanfacine (unavailable in SA)
Bupropion (Wellbutrin)
Some evidence for omega-3 fatty acid supplementation
Anxiety Disorders of Childhood
■ Generalised Anxiety Disorder
■ Separation Anxiety Disorder
■ Social anxiety disorder (social phobia)
■ Selective mutism
■ Panic Disorder
■ Agoraphobia
■ Specific phobia
■ Obsessive Compulsive Disorder
■ PTSD
‘paediatric anxiety
disorder triad’
DSM5 Major Depressive Disorder (MDD)
■ Depressed or irritable mood; AND■ Reduced interest or enjoyment of activities; plus 4 or more of :
■ Diminished ability to think or concentrate
■ Markedly reduced energy levels
■ Insomnia or excessive sleeping
■ Decreased or increased appetite, or excessive weight gain or weight loss (or failure to achieve expected weight gain)
■ Psychomotor agitation or psychomotor slowing
■ Feelings of guilt or excessive worthlessness
■ Recurrent thought of death, suicidal thinking or suicidal behaviour
These symptoms must persist for 2 weeks or more
and cause significant functional impairment
Psychotic depression
■ Presence of hallucinations
■ May include command hallucinations (suicide)
■ Less commonly delusions
■ Associated with:
■ family history bipolar disorder
■ More severe depression
■ Resistance to antidepressants
■ Increased risk of bipolar disorder
Selective serotonin uptake inhibitors (SSRI)
First choice medications for both anxiety and depression:
Fluoxetine (Prozac, Lorien, Nuzak) [FDA approved]
Paroxetine (Aropax)
Sertraline (Zoloft, Sertra, Serdep)
Citalopram (Cipramil, Cilift)
Escitalopram (Cipralex, Lexamil)
Fluvoxamine (Luvox, Favrin)
Little evidence for one over the other in the various disorders
receptor
Serotonin
SERT
the serotonergic synapse
Direction of transmission
Side-effects GIT
Nausea, vomiting
Diarrhoea
Stomach cramps
Headaches
Tiredness
Sleep disturbance
Appetite disturbance, weight gain
Behavioural activation (‘superman syndrome’) Disinhibition
Defiance
Impulsivity
Insomnia
Mania
Treatment-emergent suicidality
2004: Black box warning
But more recent data including meta-analyses suggests that
SSRI’s are safe and effective
Other medications: anxiety
Some evidence:
Tricyclic antidepressants (clomipramine/Anafranil)
beta blockers (propranolol /pur-bloka/inderal) for performance anxiety
etifoxine (Stresam)
Benzodiazepines
Clobazam (urbanol), Alprazolam (zanor)
May be used in the short-term
Habit –forming
Cause drowsiness, impaired memory
No evidence:
Rescue
Biral But very high placebo response rate in children
Other medications: depression
Evidence-based:
SNRI:
Venlafaxine (efexor, venlor)
Duloxetine (Cymbalta, cymgen)
DRI:
Bupropion (Wellbutrin)
No evidence:
tricyclic antidepressants (imipramine/Tofranil) have not been shown to
be superior to placebo
Other medications: psychotic depression
Atypical antipsychotics
Risperidone (Risperdal, zoxadon, risnia)
Aripiprazole (Abilify, arizofy)
Quetiepine (Seroquel, dopaquel)
Olanzepine (Zyprexa)
As an augmentation strategy, ie together with antidepressant
Childhood Bipolar Disorder
Recurrent episodes of depression and
MANIA:
Grandiosity/defiance
Euphoria
Irritability
Less need for sleep
Flight of ideas/ racing thoughts
Excessive involvement in pleasurable activities
Medications for Bipolar D
Mood stabilisers
Atypical antipsychotics
Anticonvulsants (eg Valproate) (Epilim), Lamotrigine (Lamictin)
Lithium (Camcolit)
Stimulants as used for ADHD
Antipsychotic mood stabilisers
‘atypical antispsychotics’
Risperidone (Risperdal, zoxadon, risnia)
Aripiprazole (Abilify, arizofy)
Quetiepine (Seroquel, dopaquel)
Olanzepine (Zyprexa)
As a group, the most effective
Side-effects of antipsychotics
Short-term
Somnolence
Dystonic reaction
Long-term
Increased appetite (weight gain)
Increased prolactin
Gynecomastia in boys
Amenorrhoea and or/galactorrhea in girls
Tardive dyskinesia
Anticonvulsant mood stabilisers
Lamotrigine (Lamictin, Epitec)
Well-tolerated, no weight gain
Potential rash, Stevens Johnson syndrome
Sodium valproate (Epilim, Convulex, Navalpro)
Potential weight gain, liver dysfunction
Carbamazepine (Tegretol)
Potential weight gain, white cell count suppression
Lithium (Camcolit)
Only after other agents have been tried
Requires regular blood tests
Thyroid
Kidneys
Lithium levels (Narrow therapeutic index)
Monitoring of treatment: general principles
Must involve collateral information:
Regular teacher feedback
Rating scales
Comorbidity: the rule rather than the exception
Polypharmacy
Initiate one medication at a time
Comorbidity: the rule rather than the exception
40%
38%11%
14%
Jensen, P et al, 1999
ODD
Mood/Anxiety
Tic
Conduct
Monitoring medication: ADHD
Monitor height, weight
Monitor blood pressure, pulse
How long to treat for?
In two-thirds of cases, ADHD persists into adulthood
Monitoring of treatment: Depression and Anxiety
How long to continue treatment?
Very little evidence-based guidance
At least 1 year following remission
Attempt discontinuation at a stress-free time of year
But chronic untreated anxiety disorders carry a worse long-term
prognosis; and
Each successive depressive relapse worsens the long-term
prognosis
Monitoring of treatment: Bipolar disorder
A mood diary may be useful, for child and/or parents
Childhood bipolar is not necessarily continuous with adult bipolar
disorder
Discontinuation of medication may be possible, only after at least
a year of remission
Weaning medication
Slowly
One medication at a time
Choose timing carefully
Take-home message
Medication is an effective, evidence-based treatment for common
childhood psychiatric conditions, provided:
1. It is used as part of a holistic treatment plan;
2. Necessary consent has been obtained
3. It is carefully monitored for efficacy, which entails collateral
information;
4. It is carefully monitored for side-effects, both short and long term