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 Conferences x x x x x x x x Advisory x x x boards
Outline 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
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: Collect a group of kids reliably diagnosed with the condition. The group must be large 1. enough to provide meaningful results. Randomly split them into two groups 2. One group receives the tested treatment, the other (control group) takes fake pills. The 3. 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 The placebo response is typically very high in children (30-60%), and many well- 4. designed trials have struggled to show that the tested treatment actually beats placebo After a reasonable time period, say four weeks, I measure how each group has done 5. (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 4 HRS Methylphenidate HCI Douglas Long acting LA Ritalin (10, 20, 30, 40mg): 6-8 HRS Extended release methylphenidate Concerta (oros-methylphenidate) Neucon 10-12 HOURS 18, 27, 36, 54mg Contramyl
Direction of transmission DRD4 DAT1 X Dopamine
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 Spencer 2013 Functional MRI Stimulants enhance activation of prefrontal cortex during cognitive tasks (more normal) Rubia 2014
‘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) 80 70 60 50 40 30 20 10 0 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 ‘paediatric anxiety ■ Separation Anxiety Disorder disorder triad’ ■ Social anxiety disorder (social phobia) ■ Selective mutism ■ Panic Disorder ■ Agoraphobia ■ Specific phobia ■ Obsessive Compulsive Disorder ■ PTSD
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
the serotonergic synapse Direction of transmission receptor SERT Serotonin
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
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