marcie hall, m.d. department of child and adolescent psychiatry university hospitals case medical...
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Marcie Hall, M.D.Department of Child and Adolescent Psychiatry
University Hospitals Case Medical Center
Autism SummitOctober 10, 2008
Medication Use in The ASD Population
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Topics Clinical features of Autism Spectrum
Disorders Areas of problematic behaviors Treatment options Medications Future Directions
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Autism Spectrum Disorders Five conditions: Autism Asperger’s Disorder Pervasive Developmental Disorder
Not Otherwise Specified Rett’s Disorder Childhood Disintegrative Disorder
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PDD’s - Core Features
Three main areas of dysfunction: Socialization Communication Restricted, repetitive stereotyped
patterns of behavior
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Epidemiology
Autism Asperger’s PDD NOS
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Treatments
There is no pharmacologic cure for the Autism Spectrum Disorders
Treatment requires a multimodal approach
Behavioral, educational, rehabilitative, support for family
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Symptomatic Treatments
Inattention, Hyperactivity, Impulsivity Irritability Aggression Self-injurious Behaviors Stereotypy and Repetitive Behaviors Sleep Disturbance Core Social and Communication
Impairment
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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
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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
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Non-Stimulant Treatments
Atomoxetine (Strettera) Again, few studies and highly variable responses. Not as much improvement and some increase in side effects compared to typically-developing children
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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.
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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
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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
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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
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Irritability, Aggression and Self-Injurious Behaviors
Atypical Antipsychotics Risperidone (Risperdal) Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel) Ziprasidone (Geodon Aripiprazole (Abilify)
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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.
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Irritability, Aggression and Self-Injurious Behaviors
Side effects of many of the Atypical Antipsychotics (Olanzapine, Risperidone, Quetiapine) include: Weight gain Mild to moderate increase in appetite Fatigue, drowsiness, sedation Constipation Metabolic problems
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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
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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)
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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
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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®)
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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.
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Stereotypic and Repetitive Behaviors
Side effects of SSRI’s: Mild sedation, lethargy Nausea Change in appetite Insomnia Behavioral activation Akathisia
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FDA Mandated Warning
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SSRI & Suicidal Ideation 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
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Stereotypic and Repetitive Behaviors
Clomipramine: a tricyclic
antidepressant, very helpful, but
concerns about side effects
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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
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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
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Deficits in Social Behavior
Medications needing more study:
D-Cycloserine
Tetrahydrobiopterin
Oxytocin
TADS, 2007
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Deficits in Social Behavior
Medications NOT effective: Fenfluramine Naltrexone
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Complementary and Alternative Medicine
Mind-body Supplements Omega 3 fatty acids Gluten free, casein free diet Secretin GI medications Auditory integration, music therapy
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Complementary and Alternative Medicine
Unconventional: Hyperbaric oxygen Chelation Immune therapies Antibiotics, antifungals
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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.