children Dr Brendan Belsham Child and adolescent psychiatrist - - PowerPoint PPT Presentation
Psychotropic medications for children Dr Brendan Belsham Child and adolescent psychiatrist www.drbelsham.com Disclosures Lund Janssen Novartis Shire Lilly Cipla Adcock Mylan Pharma beck plan Speakers x x honoraria x
Dr Brendan Belsham Child and adolescent psychiatrist www.drbelsham.com
Lund beck Janssen
Novartis
Shire
Lilly Cipla Adcock Mylan Speakers honoraria x
x x
Conferences
x x x x x x x x
Advisory boards
x x x
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
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
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
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
The use of medication for an age-group for which it is not
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
Eg Risperidone in ADHD
The ‘biopsychosocial’ approach (add spiritual) Medication is not always required, and is usually only instituted
The perils of medical reductionism
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
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
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
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
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
Growth Brain structure Later substance abuse
Consensus is that stimulant treatment can slow
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
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
ADHD is itself associated with an increased risk of substance
Poor impulse control Academic underachievement Low self-esteem Comorbid anxiety, conduct disorder
Treating ADHD in no way aggravates the risk if later substance
Substance abuse in unmedicated and medicated ADHD and control adolescents (>15 years)
10 20 30 40 50 60 70 80 Unmedicated Medicated Control Biederman, 1999
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
Appetite suppression Sleep disturbance or somnolence Constipation Mood effects especially irritability
Alpha-2 agonists
Clonidine (Dixarit, Menograine) Guanfacine (unavailable in SA)
Bupropion (Wellbutrin) Some evidence for omega-3 fatty acid supplementation
■ 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’
■ 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
■ 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
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
Direction of transmission
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
But more recent data including meta-analyses suggests that SSRI’s are safe and effective
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
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
Atypical antipsychotics
Risperidone (Risperdal, zoxadon, risnia) Aripiprazole (Abilify, arizofy) Quetiepine (Seroquel, dopaquel) Olanzepine (Zyprexa)
As an augmentation strategy, ie together with antidepressant
Recurrent episodes of depression and MANIA:
Grandiosity/defiance Euphoria Irritability Less need for sleep Flight of ideas/ racing thoughts Excessive involvement in pleasurable activities
Mood stabilisers
Atypical antipsychotics Anticonvulsants (eg Valproate) (Epilim), Lamotrigine (Lamictin) Lithium (Camcolit) Stimulants as used for ADHD
‘atypical antispsychotics’
Risperidone (Risperdal, zoxadon, risnia) Aripiprazole (Abilify, arizofy) Quetiepine (Seroquel, dopaquel) Olanzepine (Zyprexa)
As a group, the most effective
Short-term
Somnolence Dystonic reaction
Long-term
Increased appetite (weight gain) Increased prolactin
Gynecomastia in boys Amenorrhoea and or/galactorrhea in girls
Tardive dyskinesia
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
Only after other agents have been tried Requires regular blood tests
Thyroid Kidneys Lithium levels (Narrow therapeutic index)
Must involve collateral information:
Regular teacher feedback Rating scales
Comorbidity: the rule rather than the exception Polypharmacy
Initiate one medication at a time
40%
38% 11% 14%
Jensen, P et al, 1999
ODD Mood/Anxiety Tic Conduct
Monitor height, weight Monitor blood pressure, pulse How long to treat for?
In two-thirds of cases, ADHD persists into adulthood
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
Each successive depressive relapse worsens the long-term
A mood diary may be useful, for child and/or parents Childhood bipolar is not necessarily continuous with adult bipolar
Discontinuation of medication may be possible, only after at least
Slowly One medication at a time Choose timing carefully
Medication is an effective, evidence-based treatment for common