Transcript Marcie Hall Autism Summit 2008

Medication Use in The ASD Population
Marcie Hall, M.D.
Department of Child and
Adolescent Psychiatry
University Hospitals Case
Medical Center
Autism Summit
October 10, 2008
Topics
 Clinical features of Autism Spectrum
Disorders
 Areas of problematic behaviors
 Treatment options
 Medications
 Future Directions
Autism Spectrum Disorders
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Five conditions:
Autism
Asperger’s Disorder
Pervasive Developmental Disorder
Not Otherwise Specified
 Rett’s Disorder
 Childhood Disintegrative Disorder
PDD’s - Core Features
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Three main areas of dysfunction:
Socialization
Communication
Restricted, repetitive stereotyped
patterns of behavior
Epidemiology
 Autism
 Asperger’s
 PDD NOS
Treatments
 There is no pharmacologic cure for
the Autism Spectrum Disorders
 Treatment requires a multimodal
approach
 Behavioral, educational,
rehabilitative, support for family
Symptomatic Treatments
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Inattention, Hyperactivity, Impulsivity
Irritability
Aggression
Self-injurious Behaviors
Stereotypy and Repetitive Behaviors
Sleep Disturbance
Core Social and Communication
Impairment
Inattention, Hyperactivity and
Impulsivity
 Attention-Deficit Hyperactivity
Disorder
 Children with PDD’s have very high
rates of ADHD symptoms
 Symptoms can impede treatment and
decrease quality of life for our patients
and their families
Treating ADHD-Like Symptoms
 Psychostimulants
 Methylphenidate: Used extensively in
typically-developing children and
adolescents with ADHD. By
comparison, ASD patients have
somewhat less symptom amelioration
and more side effects (RUPP study)
 Amphetamines: Few studies and results
were highly variable
Non-Stimulant Treatments
 Atomoxetine (Strettera) Again, few
studies and highly variable
responses. Not as much
improvement and some increase in
side effects compared to typicallydeveloping children
Non-Stimulant Treatments
 Antidepressants:
 Tricyclics like imipramine, desipramine,
amitriptyline, clomipramine, notrriptyline have
been used historically, but recent concerns
about cardiac toxicity have curbed use.
 SSRI’s: mainly used to treat depression
 Venlafaxine: two published studies have
suggested efficacy, but several reports raise
concern that restlessness is a frequent side
effect, and can increase hyperactivity.
Non-Stimulant Treatments
 Alpha-2 Adrenergic Agonists
 Clonidine (Catapres): studies have had
small sample sizes, but seem to show a
decrease in sensory responses and
oppositionality. Side effects include
sedation, fatigue, decreased activity
 Guanficine (Tenex): similar reduction in
overactivity, but caused sedation,
constipation and occasionally, sleep
disruption
Non-Stimulant Treatments
 Cholinesterase Inhibitors: Alzheimer’s
Disease Treatments
 Post-mortem studies have shown an
abnormality in the cholinergic system
in the brains of people with autism
 Donepazil
 Galantamine
 Memantine
Irritability, Aggression and
Self-Injurious Behaviors
 Typical Antipsychotics
 Many, but particularly Haloperidol, has
been used to successfully reduce
maladaptive behaviors (aggression,
temper tantrums, withdrawal,
stereotypies).
 Main concern is side effects: sedation,
acute dystonias, dyskinesias
Irritability, Aggression and
Self-Injurious Behaviors
 Atypical Antipsychotics
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Risperidone (Risperdal)
Clozapine (Clozaril)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Ziprasidone (Geodon
Aripiprazole (Abilify)
Irritability, Aggression and
Self-Injurious Behaviors
 Risperidone has been approved by the
FDA for the treatment of irritability and
aggression in children and adolescents
with autism aged 5-16 years
 Largely due to the Research Units on
Pediatric Psychopharmacology (RUPP)
Autism Network, which demonstrated a
decrease in irritability, tantrums,
aggressive, self-injurious and stereotypic
behaviors.
Irritability, Aggression and
Self-Injurious Behaviors
 Side effects of many of the Atypical
Antipsychotics (Olanzapine,
Risperidone, Quetiapine) include:
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Weight gain
Mild to moderate increase in appetite
Fatigue, drowsiness, sedation
Constipation
Metabolic problems
Irritability, Aggression and
Self-Injurious Behaviors
 Newer atypical antipsychotics, such
as Ziprasidone and Aripiprazole are
currently being studied for efficacy in
the ASD population
 They appear to be well tolerated, with
less weight gain than the older
atypicals, but may not be as effective
in reducing maladaptive behaviors
Irritability, Aggression and
Self-Injurious Behaviors
 Antiepileptics: Seizure disorders are
common in people with ASD’s.
 Further studies are needed to determine
the efficacy and safety of these
medications in the ASD population
 Divalproex Sodium (Depakote)
 Lamotrigine (Lamictal)
 Topiramate (Topamax)
Stereotypic and Repetitive
Behaviors
 Restricted, repetitive behaviors can often
interfere with treatment in the ASD
population
 These impairments are similar to the
obsessions and compulsions found in
OCD
 Improvement in this domain can
significantly improve overall outcomes for
individuals with ASD’s
Stereotypic and Repetitive
Behaviors
A mainstay of treatment has become the
SSRI’s or Selective Serotonin Reuptake
Inhibitors:
 Fluoxetine (Prozac®)
 Sertraline (Zoloft®)
 Paroxetine (Paxil®)
 Fluvoxamine (Luvox®)
 Citalopram (Celexa®)
 Escitalopram (Lexapro®)
Stereotypic and Repetitive
Behaviors
 Fluoxetine has been shown to
improve overall functioning in
patients with ASD’s, with positive
effects on language, cognition, social
relatedness and affect.
 Also, a decrease in irritability,
lethargy, stereotypy and
inappropriate speech has been
noted.
Stereotypic and Repetitive
Behaviors
 Side effects of SSRI’s:
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Mild sedation, lethargy
Nausea
Change in appetite
Insomnia
Behavioral activation
Akathisia
FDA Mandated Warning
SSRI & Suicidal Ideation
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No reports of completed suicides
Studies did not include ASD population
SSRI use associated with decreased suicide rate
Studies found no association between SSRI use
and completed suicide
Stereotypic and Repetitive
Behaviors
 Clomipramine: a tricyclic
antidepressant, very helpful, but
concerns about side effects
Sleep Disturbance
 Commonly, people with ASD’s suffer
with disturbed sleep patterns
 Insomnia: most common problem in
ASD’s, can be caused by
neurobiology, behavior, coexisting
medical disorder (GI, epilepsy) or
psychiatric disorder (anxiety),
medications, obstructive sleep
apnea, restless leg syndrome
Sleep Disturbance
 After thorough assessment to rule out
other causes, can use:
 Melatonin
 Medications used for another disorder
(epilepsy) that are also sedating
 Risperidone
 Clonidine
Deficits in Social Behavior
 Medications needing more study:
 D-Cycloserine
 Tetrahydrobiopterin
 Oxytocin
TADS, 2007
Deficits in Social Behavior
 Medications NOT effective:
 Fenfluramine
 Naltrexone
Complementary and
Alternative Medicine
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Mind-body
Supplements
Omega 3 fatty acids
Gluten free, casein free diet
Secretin
GI medications
Auditory integration, music therapy
Complementary and
Alternative Medicine
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Unconventional:
Hyperbaric oxygen
Chelation
Immune therapies
Antibiotics, antifungals
Conclusion
 Many symptoms can be helped by
currently available therapies to
improve the lives of people living
with ASD’s.
 More research is ongoing and ASD’s
have captured the imagination of
investigators around the world.