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