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Drug Treatment in 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?

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Drug Treatment in Autism

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  1. 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

  2. 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

  3. 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 Empirical The drug has worked for someone, somewhere Secretin Serotonergic drugs Slap the TV to make it work The theoretical rationale will follow Theoretical

  4. Source of treatment  risperidone thioridazine Theoretical 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

  5. 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

  6. 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 • response only in one (the main) centre of the trial • further trials did not find positive effect • fenfluramine withdrawn from the market ∵ toxicity • fenfluramine has multiple actions • depletes serotonin by increasing its release • dopamine blocker (like haloperidol) • stimulant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)

  7. 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

  8. 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

  9. 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

  10. Autism SIB naltrexone: effects are dose specific Dose 0 0.1 0.5 1.0 2.0 mg/Kg 0mg 12.5mg 25mg 50mg mg Why do we not believe in a treatment?

  11. 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

  12. Chemical structure benzodiazepines butyrophenones tricyclics Neurotransmitter action dopamine serotinin (SSRIs) acetylcholine Drug action Drugs are named by their:

  13. Tryptophan Impulse 5-hydroxy Tryptophan MAO enzymes 5-HT7 5-HT2A 5-HT1A Drug action Serotonin (5HT) (5-hydroxy tryptamine)

  14. Tryptophan Impulse clozapine MAOI 5-hydroxy Tryptophan risperidone trazodone MAO enzymes 5-HT7 fenfluramine 5-HT2A SSRIs 5-HT1A pindolol buspirone Drug action Serotonin (5HT) (5-hydroxy tryptamine)

  15. propranolol nadolol α2adrenergic (clonidine) Drug action Block dopamine D2 blockers (haloperidol) Block noradrenaline Increase serotonin SRIs 5-OH Tryptophan ACh (nicotinic) (nicotine, galantamine) Increase acetylcholine Block neuropeptides naltexone

  16. Chemical structure benzodiazepines butyrophenones tricyclics Neurotransmitter action dopamine serotinin (SSRIs) acetylcholine Clinical action antipsychotics antiepileptics antidepressants Drug action Drugs are named by their:

  17. 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 action

  18. Drug treatment Better researched More aware of adverse effects Better controlled Purer Better informed?

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