The Effectiveness of Pharmacological Treatments in Individuals with Autism

1
The Effectiveness of Pharmacological Treatments
in Individuals with Autism

• November 13, 2003
• Presentation by Chantal Bourgon

2
Outline

• History, Prevalence and Demographic Variables
• Neurochemistry, Effectiveness and Side
  Effects
  Antidepressants
• Antipsychotics
• Stimulants
• Opiate Antagonists
• Benzodiazepines
• Alpha-2-Noradrenergic Agonists
• Beta-Blockers
• Take Home Message

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History, Prevalence and Demographic Variables

• Not until the late 1950s through 1970s did
  diverse pharmacological interventions emerge for
  individuals with autism.
• The first symptoms targeted for drug treatment
  were destructive behaviours, self-injurious
  behaviours and aggression.
• Autism Society of Ohio Study (2003)
• 21.6 Antidepressants
• 14.9 Antipsychotics
• 12.5 Antihypertensives
• 11.3 Stimulants

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Cont

• 25.7 One drug
• 22.9 Two drugs
• 6.4 Three or Four drugs
• Demographic variables associated with medication
  use
• Greater age
• Severe Autism
• Severe intellectual handicap
• Housing outside the family home

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Antidepressants

• Tricyclic antidepressants
• Venlafaxine
• Target serotonergic neurotransmission
• Increase concentration of serotonin in the
  synaptic space
• Improved attention, social relatedness and
  communication
• Decrease in hyperactivity
• Improvement in restricted interest
• Side effects possible hypertension (high blood
  pressure)

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Cont

• Tricylcic antidepressant Non-selective
  serotonin re-uptake
• Clomipramine
• Prevents serotonin re-uptake
• Additional action on the dopaminergic system
• Reduction in aggression persisting for 1.7 yrs
• Improved social relatedness and
  obsessive-compulsive behaviours
• Side effects possibility for grand mal seizure
  and cardiac conduction abnormality
• Neurotoxic symptoms lead to its discontinuation

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Cont

• Selective Serotonin Re-uptake Inhibitor
• Fluoxetine
• Prevents serotonin re-uptake
• Improvement in language, cognition, mood,
  compulsive symptoms, lethargy and stereotyped
  behaviours
• Possible agitation, decrease in appetite,
  restlessness, anorexia, insomnia and increase in
  anxiety
• Children are less responsive
• Fluvoxamine
• Prevents serotonin re-uptake
• Improvement in repetitive thoughts and
  behaviours, aggression, social relatedness and
  language
• Possibility for nausea and mild sedation

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Antipsychotics

• Typical
• Haloperidol
• Block a number of postsynaptic dopamine (DA)
  receptors (D2)
• Superior to placebo in reducing stereotyped
  behaviours, withdrawal, hyperactivity, deviant
  speech and fidgetiness.
• Side effects anxiety, depression, weight gain,
  parkinsonism, cognitive blunting and fatigue
• Sedation dose dependent
• Tardive dyskinesia disappear after
  discontinuation of medication
• Prepubertal children are less responsive then
  adolescents and adults.

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Cont

• Atypical
• Risperidone
• Block DA receptors (D2) and block serotonin
  receptors
• Positive response in terms of aggression, sleep,
  self-injurious behaviours, withdrawal, mood and
  social skills.
• Improvement in disruptive behaviours for 2 yrs
  without any signs of tolerance
• Improve tardive dyskinesia
• Side effects weight gain but stabilizes with
  time
• Sedation dose dependent
• More useful in children suffering from severe and
  chronic autism

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Stimulants

• Pemoline
• Increase DA and Norepinephrine (NE) in the
  synaptic cleft
• Some studies show increase in agitation and
  repetitive behaviours
• Other studies demonstrate some effectiveness
• Side effects insomnia, weight loss, deceleration
  of growth, activation of tics in predisposed
  individuals, lower seizure threshold
• Hepatoxicity and liver failure
• Methyl phenidate
• Affect dopaminergic neurotransmission
• Decrease hyperactivity
• Need more research

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Opiate Antagonists

• Naltrexone
• Block the activity of endogenous opiate system in
  the central nervous system (C.N.S)
• Minimum reduction in hyperactivity
• No impairment in learning
• No amelioration in social , stereotyped and
  self-injurious behaviours
• No improvement in communication
• Side effects mild and transient sedation and
  gastrointestinal upset
• Bitter taste

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Benzodiazepines

• Lorazepam and Clonazepam
• Act in concert with inhibitory neurotransmitter
  GABA to stabilize and decrease the firing rate of
  neurons.
• Treat explosiveness and aggression which
  accompanies mental retardation.
• Not systematically studied for autism
• Side effects sedation, decrease reaction time,
  tolerance and dependence

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Alpha-2-Noradrenergic Agonist

• Clonidine
• Decrease NE and Epinephrine neurotransmission
• Pre-synaptic receptor agonist
• Improvement in hyperactivity, inattention,
  impulsivity, irritability, stereotyped behaviours
  and inappropriate speech.
• Side effects sedation, decrease in blood
  pressure and tolerance to therapeutic effects
• Guanfacine
• Decrease in activity, increase in arousal
• Side effects hypotension

14
Beta-Blockers

• Propanolol
• Affects the noradrenergic transmission
• Decrease impulsive and aggressive behaviours
• Decrease in stereotyped and self-injurious
  behaviours
• Improvement in attention span
• Mitigate tremors induced by other drugs (Lithium)
• Side effects, sedation, depression, drop in blood
  pressure and bradycardia (abnormally slow heart
  rate)

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Others

• Leuprolide
• Antiandrogen
• Inhibitor of gonadotropin secretion
• Suppression of public masturbation
• Decreased libido
• No sexual excitement due to contact with children
• Anticonvulsants
• Lithium
• Megavitamins
• Corticosteroids
• Secretin

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Take Home Message

• A number of classes of medication have been used
  to treat autism.
• Pharmacological treatments are primarily
  symptomatic and benefits usually fade away as the
  medications are discontinued.
• Need to increase understanding of developmental
  and neurochemical basis of autism to provide cues
  for novel use of medication.
• Medication should always be part of a
  comprehensive multidisciplinary treatment
  approach.

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References

• Aman, M.G., Lam, K.S.L., Collier-Crespin, A.
  (2003) Prevalence and patterns of
• use of psychoactive medicines among individuals
  with autism in the Autism Society of Ohio.
  Journal of Autism and Developmental Disorders,
  33, 527-534.
• Buitelaar, J.K., Willemsen-Swinkels, S.H.N.
  (2000) Medication treatment in subjects with
  autism disorders. European Child and Adolescent
  Psychiatry, 9, 185- 197.
• Fatemi, S.H., Realmuto, G.M., Khan, L., Thuras,
  P. (1998) Fluoxetine in treatment of adolescent
  patients with autism a longitudinal open trial.
  Journal of Autism and Developmental Disorders,
  28, 303-307.
• Hellings, J.A. (1999) Psychopharmacology of mood
  disorders in persons with mental retardation and
  autism. Mental Retardation and Developmental
  Disabilities Research Reviews, 5, 270-278.
• Hunsinger, D.M., Nguyen, T., Zebraski, S.E.,
  Raffa, R.B. (2000) Is there a basis for novel
  pharmacotherapy of autism? Life Sciences, 67,
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• Kerbeshian, J., Burd, L., Avery, K. (2001)
  Pharmacotherapy of autism A review and clinical
  approach. Journal of Developmental and Physical
  Disabilities, 13, 199-228.

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Cont

• Luiselli, J.K., Blew, P., Keane, J., Thibadeau,
  S., Holzman, T. (2000) Pharmacotherapy for
  severe aggression in a child with autism open
  label evaluation of multiple medications on
  response frequency and intensity of behavioural
  intervention. Journal of Behaviour Therapy and
  Experimental Psychiatry, 31, 219-230.
• Realmuto, G.M., Ruble, L.A. (1999) Sexual
  behaviours in autism Problems of definition and
  management. Journal of Autism and Developmental
  Disorders, 29, 121-127.
• Simeon, J., Milin, R., Walker, S. (2002) A
  retrospective chart review of Risperidone use in
  treatment-resistant children and adolescents with
  psychiatric disorders. Progress in
  Neuro-Psychopharmacology and Biological
  Psychiatry, 26, 267-275.
• Williams, P.G., Allard, A., Sears, L., Dalrymple,
  N., Bloom, A.S. (2001) Brief report Case
  reports on Naltrexone use in children with
  autism Controlled observations regarding
  benefits and practical issues of medication
  management. Journal of Autism and Developmental
  Disorders, 31, 103-108.