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Master Slide. Current Trends in the Pharmacological Treatment of Autism . Alexander Kolevzon, MD Peter Della Bella, MD David Grodberg, MD Charles Cartwright, MD. Symptom Domains and Associated Features of ASD. Social Phobia. Social Impairment. EEG Abnormalities. ADHD Symptoms.

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master slide

Master Slide

Current Trends in the

Pharmacological Treatment of Autism

Alexander Kolevzon, MD

Peter Della Bella, MD

David Grodberg, MD

Charles Cartwright, MD

symptom domains and associated features of asd
Symptom Domains and Associated Features of ASD

Social Phobia

Social Impairment

EEG Abnormalities

ADHD Symptoms

Asperger’s syndrome

AUTISM

Impulsivity/

Aggression

Speech/

Communication Deficits

Repetitive Behaviors

Obsessive Compulsive Disorder

Expressive/Receptive Language Disorders

adhd symptoms and autism spectrum disorders co occurrence phenomenology and treatment
ADHD Symptoms and Autism Spectrum Disorders: Co-Occurrence, Phenomenology, and Treatment

David Grodberg, M.D.

Seaver Autism Center

the treatment of anxiety and repetitive behaviors in autism spectrum disorders
The Treatment of Anxiety and Repetitive Behaviors in Autism Spectrum Disorders

Alex Kolevzon, M.D.

Clinical Director, Seaver Autism Center

future directions targeting novel neurotransmitter and hormonal systems in autism

Future DirectionsTargetingNovel Neurotransmitter and Hormonal SystemsIn Autism

Charles Cartwright, MD

Director, YAI Autism Center

master slide7

Master Slide

Agitation and Aggression

Peter Della Bella, MD

what is agitation

What is Agitation?

An inability to cope

causing distress…

and losing control

Precursors: Irritability, anxiety, fatigue…

The worry: add a trigger and…

what is aggression

What is Aggression?

(Latin) Attack

Premeditated vs. loss of impulse control

roots of irritability agitation the fight or flight response

Roots of Irritability & Agitation- the Fight or Flight Response

Sources: Babble.com; Brain-trainer.com; quantumlearningblog

roots of agitation and aggression

Roots of Agitation and Aggression

ATTACK

loss of control

agitated

coping

irritated

c a l m

roots of agitation and aggression13

Roots of Agitation and Aggression

  • Survival instinct

(“Boxed into a corner”)

  • Pain/physical discomfort

(sensory integration)

  • Psychic discomfort

(stress, change, frustration)

roots of agitation and aggression14

Roots of Agitation and Aggression

ATTACK

agitated

irritated

c a l m

roots of agitation and aggression15

Roots of Agitation and Aggression

stress, discomfort, pain

ATTACK

agitated

c a l m / irritated

roots of agitation and aggression16

Roots of Agitation and Aggression

stress, discomfort, pain

ATTACK

agitated

c a l m / irritated

cultural, behavioral, “medical” factors

what do you do

What do you do?

  • Survival instinct…….. take care of the threat
  • Treat sources of physical discomfort, side effects… proper medical evaluation sensory integration principles
  • Treat sources of psychic discomfort…..

soften the blow of change address stress (sleep, food, downtime, fun)

roots of agitation and aggression18

Roots of Agitation and Aggression

ATTACK

agitated

Irritated

c a l m

when do you use meds

When do you use meds?

  • When there are underlying biological factors. Let the

symptoms guide you!

      • Anxiety Disorder
      • Depression
      • ADHD
      • Psychosis
      • Seizure
  • Otherwise, MEDICATION IS A LAST RESORT
fda approved for autism

FDA approved for autism…

risperidone

aripiprazole

master slide23

Master Slide

Attention Deficit and Hyperactivity

David Grodberg, MD

adhd symptoms in asd
ADHD SYMPTOMS IN ASD
  • DSM-IV TR prohibits diagnosis of ADHD and ASD in the same individual
  • Clinic based surveys indicate that Sx c/w ADHD present in 41-78% of children with ASD
adhd symptoms in asd25
ADHD SYMPTOMS IN ASD
  • Asperger’s Disorder, PDD-NOS who meet full criteria for ADHD
  • Autistic Disorder with ADHD-like symptoms, which are part of core features of autism
  • Autistic Disorder with increased motor activity, impulsivity, inattention
adhd symptoms in asd26
ADHD SYMPTOMS IN ASD
  • Inattention to social stimuli but good sustained focus on interests or objects. NOT ADHD.
  • Hyperactivity as a manifestation of motor stereotypy, social anxiety, agitation, or medication side effects. NOT ADHD
treatment of adhd symptoms in asd
TREATMENT OF ADHD SYMPTOMS IN ASD
  • Strongest evidence: methylphenidate
    • 2 placebo-controlled trials
    • retrospective and prospective effectiveness study
methylphenidate
Methylphenidate

Increases NE and DA by blocking reuptake

methylphenidate29
Methylphenidate

ASD+ADHD tolerated stimulants generally well

ASD+ADHD had dysphoria and obsessionality

- initiate methylphenidate in ASD at lower dose and increase dose slowly with frequent monitoring for side effects

treatment of adhd symptoms in asd30
TREATMENT OF ADHD SYMPTOMS IN ASD
  • Moderate Level Evidence: guanfacine
    • chart review study
    • small open-label trial
  • Moderate Level Evidence: atomoxetine
    • small open label study
    • small placebo controlled study
guanfacine
Guanfacine

Alpha 2A agonist. Enhances prefrontal cortical function

atomoxetine
Atomoxetine

Increases NE and DA in prefrontal cortex.

treatment of adhd symptoms in asd33
TREATMENT OF ADHD SYMPTOMS IN ASD
  • Weak Support: clonidine, donepezil
    • very small studies
clonidine
Clonidine

Nonselective alpha2 agonist. More sedating/hypotensive.

donepezil
Donepezil

Acetyl Cholinesterase inhibitor

summary
SUMMARY
  • Children with ADHD symptoms and ASD are difficult to treat
  • stimulants (methylphenidate), atomoxetine, alpha-agonists are effective
  • SSRIs and atypical neuroleptics are used to address other types of symptoms
clinical pearls
CLINICAL PEARLS
  • If a child with ADHD is referred with poor response to meds and/or significant side effects (anxiety, stereotypy, aggression) - look for evidence of previously unrecognized ASD
  • If a stimulant is helpful but side effects of anxiety emerge, can switch to atomoxetine or add SSRI.
  • Monitor closely for behavioral disinhibition
    • hyperactivity, impulsivity, new odd/disorganized behavior, SI.
master slide38

Master Slide

Anxiety and Repetitive Behaviors

Alexander Kolevzon, MD

repetitive behaviors

Repetitive Behaviors

A preoccupation with stereotyped and restricted patterns of interest

Inflexibility in adhering to routines and rituals

Stereotyped and repetitive motor mannerisms

Persistent preoccupation with parts of objects

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)

repetitive behaviors40

Higher Order (compulsive)

Insistence on sameness

Ritualistic behavior

Circumscribed interests &

preoccupation

Repetitive Behaviors

Lower Order (motor/sensory)

Repetitive self-injury

Motor stereotypies

Sniffing/mouthing objects

Touching

Tapping

Rubbing

repetitive behaviors41

Higher Order (compulsive)

Obsessions

Repetitive Behaviors

Lower Order (motor/sensory)

Hoarding

Anagnostou et al, 2005

serotonin system
Serotonin System
  • Critical to neurodevelopment
  • Directs neuronal growth,

proliferation, differentiation

  • Widely expressed in

emotional centers of

brain

novel therapeutics oxytocin

Novel Therapeutics - Oxytocin

Widely distributed in Central Nervous System; especially emotional centers

Peripheral release is important for delivery and lactation

Central release is important for social cognition (recognition and memory); trust; social attachment; maternal bonding

iv oxytocin challenge

need to know

  • repeating
  • ordering
  • need to tell
  • self-injury
  • touching

IV Oxytocin Challenge

Hollander et al, 2003

master slide54

Master Slide

Future Directions

Charles Cartwright, MD

caution
Caution

Demonstrate Safety and Efficacy

master slide69

Master Slide

THANK YOU

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