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Drug Treatment in AutismDrug Treatment in Autism
Tom BerneyNorthgate & Prudhoe NHS Trust
Fleming Nuffield Child & Family Psychiatry UnitEuropean Services for People with Autism (ESPA)
Athens University visitAthens University visit
Source of treatmentSource of treatment empirical theoretical
Does treatment work?Does treatment work? fenfluramine & secretin Why do we believe / not believe?
Drug Treatment in AutismDrug Treatment in Autism
How we think of drugs - their actionHow we think of drugs - their action
Source of treatmentSource of treatment
EmpiricalEmpirical
TheoreticalTheoretical
The drug has worked for someone, somewhere
The person has an abnormality (biochemical / electrical) that the drug might correct
It is similar to another disorderfor which the drug has worked
Slap the TV to make it work SecretinSerotonergic drugs
The theoretical rationalewill follow
TheoreticalTheoretical
haloperidolchlorpromazine
It is similar to another disorderfor which the drug has worked
Autism = schizophrenia ∴ neuroleptics
risperidonethioridazine
The person has an abnormality that the drug might correct
Autism = opiate addiction ∴ naltrexone
Raised serotonin ∴ fenfluramine
Inflamed bowel ∴ sulfasalazine
epileptic EEG ∴ AEDs / surgery
Source of treatmentSource of treatment
Source of treatment empirical theoretical
Does treatment work?Does treatment work? fenfluramine & secretin Why do we believe / not believe?
Drug Treatment in AutismDrug Treatment in Autism
How we think of drugs - their action
fenfluramine
3 people with autism had high serotonin levels in CSF– their autism improved with fenfluramine
30% people with autism had high serotonin levels fenfluramine effective in multicentre trial
response only in one (the main) centre of the trial further trials did not find positive effect fenfluramine withdrawn from the market ∵ toxicity fenfluramine has multiple actions
• depletes serotonin by increasing its release• dopamine blocker (like haloperidol)• stimulant (like methylphenidate)
Does treatment work?Does treatment work?
secretin
secretin given to a 10 yr child with autismas a test of pancreatic function– autism improved
2 other children responded - publication widespread use with enthusiastic media reports
double-blind RCT trial • 44% children responded to secretin infusion• 40% children responded to saline placebo
subsequent controlled trials confirmed the power of the placebo
Does treatment work?Does treatment work?
Why do we believe in a treatment?Why do we believe in a treatment?
Difficulty in measuring the response
Instruments rate diagnosis > severity/change
Short-term: day to day variation
Long-term: developmental change
Powerful placebo response
Passionate support for treatment
Why do we not believe in a treatment?Why do we not believe in a treatment?
If a drug works – the response will be:
Inconsistent • in some people• for some symptoms
Transient – tolerance inevitable
To a very specific dosage• very sensitive / insensitive to the drug• a dosage window (Goldilocks effect)• a paradoxical effect
SIBAutism
0mg 25mg 50mg12.5mg mg
Why do we not believe in a treatment?Why do we not believe in a treatment?
Dose0 0.1 0.5 1.0 2.0 mg/Kg
naltrexone:effects are dose specific
Source of treatment empirical theoretical
Does treatment work? fenfluramine & secretin Why do we believe / not believe?
Drug Treatment in AutismDrug Treatment in Autism
How we think of drugs - their actionHow we think of drugs - their action
Drug actionDrug action
Drugs are named by their:
Chemical structure benzodiazepinesbutyrophenonestricyclics
Neurotransmitter action dopamineserotinin (SSRIs)acetylcholine
Impulse
5-HT1A
5-HT2A
5-HT7
MAO enzymes
Tryptophan
5-hydroxyTryptophan
Serotonin (5HT)Serotonin (5HT) (5-hydroxy tryptamine)
Drug actionDrug action
Impulse
MAO enzymes
MAOI
5-HT1A
5-HT2A
5-HT7
SSRIs
fenfluramine
trazodone
risperidone
clozapine
buspirone
pindolol
Tryptophan
5-hydroxyTryptophan
Serotonin (5HT)Serotonin (5HT) (5-hydroxy tryptamine)
Drug actionDrug action
Block dopamine
Increase serotonin
Block neuropeptides
Block noradrenaline
SRIs 5-OH Tryptophan
D2 blockers (haloperidol)
α2adrenergic(clonidine)
propranololnadolol
ACh (nicotinic)(nicotine, galantamine)
Increase acetylcholine
naltexone
Drug actionDrug action
Drug actionDrug action
Chemical structure benzodiazepinesbutyrophenonestricyclics
Neurotransmitter action dopamineserotinin (SSRIs)acetylcholine
Clinical action antipsychoticsantiepilepticsantidepressants
Drugs are named by their:
Drug actionDrug action
balanced systems > an isolated systembalanced systems > an isolated system
acting on different areas of the brainacting on different areas of the brain
interaction between drugsinteraction between drugs
Clinical action is the sum of several effectsClinical action is the sum of several effects
Wide range of effects from single drugWide range of effects from single drug
primary effectprimary effect
side (adverse) effectsside (adverse) effects
Drug treatmentDrug treatment
Better researched
PurerBetter controlled
More aware of adverse effects
Better informed?