Transcript Drug treatment in Autism - Autism

Drug Treatment in Autism
Tom Berney
Northgate & Prudhoe NHS Trust
Fleming Nuffield Child & Family Psychiatry Unit
European Services for People with Autism (ESPA)
Athens University visit
Drug Treatment in Autism
Source of treatment
 empirical
 theoretical
Does treatment work?
 fenfluramine & secretin
 Why do we believe / not believe?
How we think of drugs - their action
Source of treatment
Empirical
The drug has worked for someone, somewhere
Slap the TV to make it work
The theoretical rationale
will follow
Secretin
Serotonergic drugs
Theoretical
It is similar to another disorder
for which the drug has worked
The person has an abnormality
(biochemical / electrical) that the drug might correct
Source of treatment
Theoretical
risperidone
thioridazine
It is similar to another disorder
for which the drug has worked

haloperidol
chlorpromazine
Autism = schizophrenia ∴ neuroleptics
Autism = opiate addiction ∴ naltrexone
The person has an abnormality
that the drug might correct
Raised serotonin ∴ fenfluramine
Inflamed bowel ∴ sulfasalazine
epileptic EEG ∴ AEDs / surgery
Drug Treatment in Autism
Source of treatment
 empirical
 theoretical
Does treatment work?
 fenfluramine & secretin
 Why do we believe / not believe?
How we think of drugs - their action
Does treatment work?
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
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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fenfluramine withdrawn from the market ∵ toxicity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?
secretin
 secretin given to a 10 yr child with autism
as 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
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?
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
Why do we not believe in a treatment?
Autism
SIB
naltrexone:
effects are dose specific
Dose
0 0.1
0mg
0.5
12.5mg
1.0
25mg
2.0 mg/Kg
50mg mg
Drug Treatment in Autism
Source of treatment
 empirical
 theoretical
Does treatment work?
 fenfluramine & secretin
 Why do we believe / not believe?
How we think of drugs - their action
Drug action
Drugs are named by their:
Chemical structure
benzodiazepines
butyrophenones
tricyclics
Neurotransmitter action
dopamine
serotinin (SSRIs)
acetylcholine
Drug action
Tryptophan
Impulse
5-hydroxy
Tryptophan
MAO
enzymes
5-HT7
5-HT2A
5-HT1A
Serotonin (5HT)
(5-hydroxy tryptamine)
Drug action
Tryptophan
clozapine
Impulse
risperidone
MAOI
5-hydroxy
Tryptophan
trazodone
5-HT7
5-HT2A
5-HT1A
pindolol
MAO
enzymes
fenfluramine
SSRIs
buspirone
Serotonin (5HT)
(5-hydroxy tryptamine)
Drug action
Block dopamine
D2 blockers (haloperidol)
Block noradrenaline
propranolol
nadolol
Increase serotonin
SRIs
Increase acetylcholine
ACh (nicotinic)
(nicotine, galantamine)
Block neuropeptides
naltexone
α2adrenergic
(clonidine)
5-OH Tryptophan
Drug action
Drugs are named by their:
Chemical structure
benzodiazepines
butyrophenones
tricyclics
Neurotransmitter action
Clinical action
dopamine
serotinin (SSRIs)
acetylcholine
antipsychotics
antiepileptics
antidepressants
Drug action
Clinical action is the sum of several effects
balanced systems > an isolated system
acting on different areas of the brain
interaction between drugs
Wide range of effects from single drug
 primary effect
 side (adverse) effects
Drug treatment
Better researched
More aware of adverse effects
Better controlled
Better informed?
Purer