Transcript A Diagnostic and Management Approach to Autism and other

An Approach to the Child
with an Autism Spectrum
Disorder
A. A. Golombek, MD
Attending, Seattle Children’s Hospital
Consulting Psychiatrist, PAL Program
May 5, 2012
PAL Conference
Disclosures

This talk includes the presentation of off-label
medications indicated by an asterisk (*)

This talk is designed for primary care providers.
It does not provide medical advice for individual
patients and is not a substitute for care.

Financial disclosures: None.
May 5, 2012
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Conceptual Foundation
 Unusual
group of children described by
Kanner in 1943:
 They lacked the ability or interest to “relate
themselves in the ordinary way to people
and situations.”
(Frith, 2003)
 Language
was a struggle: they misused
pronouns, were excessively literal, limited
to mimicry, or mute.
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
Change was a trial: they demonstrated an
intense desire and need for sameness, whether
in behavior, interests, or events in a day.

They struggled to see the forest form the trees,
“to experience wholes without full attention to
constituent parts.”
(Happe, 2005)

They reacted unusually to physical sensation,
either too little or too much.
(Volkmar, Klin, 2005)
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Theory of Mind

Realization that each person has individual
thoughts.

Typically develops around the mental age of 5.

In children with autism, develops later or not at
all.

Examined through tests of false belief.
(Frith, 2003)
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Theory of Weak Central Coherence

Understanding general concepts or principles is
impaired.

Strength is in focus and memory of specific
situations.

May be linked to executive functions.

Strongly influences learning style.
(Frith, 2003)
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Shared Joint Attention
 Impairments
in ability of coordinating
another’s attention with one’s one.
 Likely
one of the foundations necessary
for socialization, language formation, and
learning.
(Mundy, Burnette, 2005)
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Prevalence
 Increasing
from 4.7/10,000 from 1966 to
1993 to 12.7/10,000 from 1994 to 2000.
(Frombonne, 2005)
 As
high as 2.64% in a recent populationbased sample.
(Kim, et
al, 2011)
 Some
of increase likely due to increased
awareness and broader phenotype (from
which most of increase arises.)
(Frombonne, 2005)
May 5, 2012
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Causes of Autism

Autism is heterogeneous disorder. Thus, it is unlikely
that there will be a single cause or a single cure.

Possible contributors include genetic factors,
neurotransmitters, metabolic disorders, and mitochondrial
abnormalities, among others.

Evidence for a causal role for MMR vaccines or mercury
levels is lacking.
May 5, 2012
(Hussain, 2007)
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When to Screen
 Per



the American Academy of Pediatrics:
During well child checkups, especially at 18 or 24
months.
If there is a concern by a parent, care-giver or
pediatrician for social development or communication.
If there is a sibling with autism, which greatly
increases the risk.
(Johnson, 2007)
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Screening Questions





Does child meet the gaze of others?
Does her or she mimic expressions or smile socially?
Does child engage when parents talk to them or try to
play with them?
Does he or she orient to his or her name by 1 year?
Does he or she point to things or bring things to
share?
(Zwaigenbaum, 2005)
May 5, 2012
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Comprehensive Assessment

Autism

Communication and Socialization Deficits

Cognition, including Executive Function

Adaptive Function and Readiness for the Future

Sensory and Motor Abnormalities

Medical and Neurological Illness

Psychiatric Concerns
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Diagnosing Autism

In the primary care system:

DSM criteria-IV-TR.

May supplement with a screening or assessment tool.
• 16-18 months: Modified Checklist for Autism in Toddlers (M-CHAT), 5-10
minute parent questionnaire, Sens/Spec: 0.85/0.93, at www.firstsigns.org
(Search “M-CHAT” then “Scoring M-CHAT”
• 4-11 years: The Childhood Autism Spectrum Test (CAST), 10 minute parent
questionnaire, Sens/Spec: 0.88/0.97, at
www.autismresearchcentre.com/tests
• 12-15 years: The Adolescent Autism Spectrum Quotient (AQ), 15 minute
parent questionnaire, Sens/Spec: 0.89/1.0, at
www.autismresearchcentre.com/tests
(Johnson, 2007)

In Autism centers:

Autism Diagnostic Interview-Revised and Observation Scale (ADI-R,
ADOS) may be used.
• Especially helpful for children who are less than 2 years old or have
intellectual disabilities.
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From the DSM-IV-TR, 2000

6 symptoms in impairments in social interactions,
language and repetitive interests or behavior.

Hallmark’s of Rett’s Disorder:







Apparently normal prenatal, head circumference, psychomotor
development until 5 months of age.
Deceleration of head growth between 5 and 48 months.
Loss of purposeful hand skills and development of stereotyped hand
movements (hand-wringing or hand-washing).
Poorly coordinated gait and trunk movements.
Severely impaired language and severe psychomotor retardation.
Loss of social engagement.
Hallmark’s of Child Disintegrative Disorder:



Apparent normal development until the age of 2 years.
Loss of skills (before age 10) in language, social skills or adaptive
function, play, bowel or bladder control, or motor skills (2 or more sx.)
Impairments in social interactions, language, and repetitive interests or
behavior (2 or more sx.)
(DSM-IV-TR, 2000)
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Qualitative Impairment in Social
Interaction (at least 2 sx)
1. Marked impairment in nonverbal behaviors (gaze,
posture, expression.)
2. Failure to develop peer relationships appropriate to
developmental level.
3. Lack of spontaneous seeking to share enjoyment,
interests, or achievements with others (by pointing,
bringing, showing objects of interest.)
4. Lack of social or emotional reciprocity.
(DSM-IV-TR, 2000)
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Qualitative Impairment in
Communication (at least 1 sx)
1. Delay in or lack of development of spoken language
without compensation.
2. Marked impairment in the ability to initiate or sustain
conversation.
3. Stereotyped, repetitive, or idiosyncratic use of language.
4. Lack of varied, spontaneous make-believe or social
imitative play appropriate to level.
(DSM-IV-TR, 2000)
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Restricted, Repetitive, Stereotyped
Behavior, Interests, and Activities
(at least 1 sx)
1. encompassing preoccupation with stereotyped or restricted
patterns of interest abnormal in intensity or focus.
2. Apparently inflexible adherence to specific, non-functioning
routines or rituals.
3. Stereotyped and repetitive motor mannerisms (hand
flapping.)
4. Persistent preoccupation with parts of objects.
(DSM-IV-TR, 2000)
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Asperger’s Disorder
Qualitative impairment in social interaction (at least 2 sx.)
Restricted, repetitive behaviors (at least 1 sx.)
No delay in language (single words by 2, phrases by 3.)
No cognitive delays or delays in adaptive function.
Still causes significant impairment in function.
(DSM-IV-TR, 2000)
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Pervasive Developmental Disorder
(PDD) NOS

Severe and pervasive impairment in the development of
reciprocal social interaction associated with impairment
in verbal or nonverbal communication skills or the
presence of stereotyped behaviors, interests, or
activities.
(DSM-IV-TR, 2000)
May 5, 2012
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Wyoming Resources

Wyoming Department of Developmental
Disabilities
(http://wdh.state.wy.us/DDD/index.html)

Wyoming Parent Information Resource (PIRC)
for assistance raising children with disabilities:

Education Network:
• http://www.npen.net (307-684-7441)

Information Calendar:
• http://www.wpic.org (307-684-2277)
May 5, 2012
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Treatment for Autism

No medication to target core deficits.

No method of behavioral intervention with success > 50-70%.
(Schreibman, Ingersoll, 2005)

However, early and intense intervention has been shown to modify
the course of autism
(Faja, Dawson, 2006)

US National Research Council’s Principles for Effective Intervention:
early; intense (25 hrs/wk); repeated, planned, brief sessions; 1:1 or
small group; parent involvement and training; and mechanisms to
evaluate and modify progress.
(Myers, 2007)
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Applied Behavioral Analysis (ABA)

Skills learned through


Prompting, shaping, reinforcement, and repetition.
Emphasis on functional routines
• taught by breaking tasks down into simple and
discrete steps,
• then “chaining” them together.
(Arick et al, 2005)

Most successful programs draw from this
approach.
May 5, 2012
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Communication and Socialization

Addressing deficits is key to improving function
and prognosis.

Always consider when addressing maladaptive
behavior.

Speech and Language evaluation (including
expressive and receptive language, processing
speed, and for children with suspected ASD,
social or pragmatic language skills.)
May 5, 2012
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Speech & Language Interventions

For non-verbal children, Picture Exchange Communication System
or sign language may help.

Simplify language. Use short sentences. Avoid nuance, sarcasm,
double-meanings, non-verbal gestures.

Pair verbal instructions with visual aides.

Don’t confuse the child with affect: be calm and clear.

Social stories (cartoons that rehearse social situations.)

Role-playing with concrete problem-solving (such as, “When I don’t
want to do something, I will tell my teacher.)

Social skills groups.
May 5, 2012
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Cognition and Executive Function

In ASD prevalence of Intellectual Disability (ID)
ranges from 70-80% to 22-52%.

Intellectual ability is a strong predictor of
prognosis.
(Shea, Mesibov, 2005)

Executive function skills are often impaired.
May 5, 2012
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Strategies to Improve Executive
Function









Simplify tasks into discrete, concrete steps.
Usual visual aids (pictures, schedules, check-off lists.)
Use hand’s on learning (see one, do one, repeat as
necessary)
Prepare for transitions and new experiences.
Decrease distractions.
Decrease stressors.
Coordinate assignments.
Consider assessment for ADHD symptoms and
treatment if warranted.
Challenges should be a good match for abilities.
May 5, 2012
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Adaptive Function

Often lags behind cognitive function.

May facilitate additional services, especially if
cognitive deficits are insufficient.

Need to incorporate adaptive functions as goals
of education.
(Lord, Corsello, 2005)
May 5, 2012
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Adaptive Issues in Life

Most individuals with autism do not live independently as
adults, but live with family or in supportive environments.
(Howlin, 2005)

Up to 75% of adults with any disability are unemployed
despite wanting to work, despite programs that
demonstrate even very low functioning individuals can
work.
(Gerhardt, 2005)

Consider sheltered facilities, work coaches.

Educational Mandates:


Federal law mandates assistance with transition planning.
May start at as early as 14 year old, but no later than 16.
(Gerhardt, 2005)
May 5, 2012
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Sensory or Motor Problems

Sensory sensitivities (or lack thereof) may provoke
maladaptive behaviors.

Unfortunately, there is a paucity of evidence for methods
that attempt to address primary deficit.
(Baranek et al, 2005)

Consultation with an Occupational Therapist can help.

Practical Solutions:

Sensitive to noise? Consider ear muffs or access to a
quiet room.

Scratchy tag? Remove it

Problematic behaviors (chewing, scratching self)?
Consider a substitute activity and try to determine
what triggers and reinforces the behavior.
May 5, 2012
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Medical Evaluation

Guided by clinical presentation & symptoms including loss of skills,
focal neurological findings, family history, etc.

Check vision and hearing.

Consider lead and Fragile X if Intellectual Disability is suspected.

Ensure child receives normal medical care including dental care.

Always assess for pain (ear aches, dental pain, stomach aches,
etc) especially when there is a change in behavior.

Gastrointestinal and sleep issues are common.

Not routinely recommend:

Celiac antibodies, allergies to gluten, casein, molds; vitamin
and trace element analysis, and intestinal permeability studies
or stool analysis.
May 5, 2012
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(Filipek, 2005)
Neurological Evaluation

Always consider if there is a loss of previously
acquired skills.

Consider EEG if seizures.

Seizures are present in 1/3 of individuals with autism.

Peak onset is before 5 years old and between 10 and 12
years old.

Function in ASD may improve significantly with treatment
of seizures.
(Minshew et al, 2005)
May 5, 2012
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Psychiatric Disorders
in Children with ASD

Paucity of systematic studies of incidence, but
estimates range from 4-58%

Anxiety & Depression most common (up to 1/3)

Similarly, deficits in executive function and
attention common.

No difference in prevalence of schizophrenia.
(Howlin, 2005)
May 5, 2012
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Diagnostic Difficulties

Under-reporting of symptoms in children whose
abilities to identify or communicate emotions, or
understand abstract concepts are compromised.

Some symptoms of psychiatric disorders can
also be seen with ASD including poor eyecontact, flat affect, social withdrawal,
impoverished or concrete thought, unusual
movements, and repetitive behavior.
(Howlin, 2005)
May 5, 2012
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Assessment: Rule out medical causes,
especially if new-onset
 Pain.
 Medication

side-effects:
Disinhibition, akathisia, agitation, confusion,
dystonias or dyskinesias, new-onset or
increased seizures (remember that many
psychotropic medications lower the seizure
threshold.)
 Drug-drug
interactions.
 Seizures.
May 5, 2012
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Assessment: Consider Stressors

Changes in care-givers, home, school, routines, and
transitions.

Lack of support, teasing, bullying, neglect, and abuse.

Environmental conditions: too noisy, too chaotic, too
crowded, etc.

Inappropriate task demands: too demanding vs. boring.

Inadequate communication.

Inadequate coping skills.
May 5, 2012
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Functional Analysis of Behavior

Causes of behavior:


If random, consider medical or neurological cause.
If not random, it is likely an attempt to communicate or is somehow
functional.

Is the behavior an attempt to communicate? “I’m scared, mad,
frustrated, irritated, sad, or overwhelmed!”

Does the behavior result in a gain?


Getting something one wants? Attention, a toy, or a treat?
Getting out of a situation one finds unpleasant or overwhelming?

Identify nature, timing, frequency, and duration of behavior.
Establish baseline.

Identify triggers and reinforcements.
May 5, 2012
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Recommended Approach to
Treatment

When possible, identify a specific psychiatric
diagnosis.

When not possible, identify specific target
symptoms.

Obtained informed consent from the patient if
they have capacity. If not, still provide
developmentally appropriate explanations of
risks, benefits, and alternatives.
May 5, 2012
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Interventions

Educate individuals and care-givers.

Address stressors.

Increase communication skills.

Increase coping skills.

Behavior Therapy (modifying triggers and reinforcements)

Consider other evidence-based therapies as appropriate to disorder,
symptom, and developmental abilities.

Consider medications in the context of the above interventions, but
not as an isolated intervention.
May 5, 2012
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Medication

No medication to target core deficits of autism.

Limited data.

Differences in response:
 Expect decreased efficacy.
 Expect increased adverse effects (agitation, irritability,
aggression, disinhibition, dystonias, dyskinesias, etc.)

Start low and go slow, tracking response.

Maximum doses less than or equal to for the typically
developing.
May 5, 2012
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Avoid pitfalls

Track responses to intervention.

Distinguish between a partial positive response and
tolerance to adverse effects.

If a given intervention isn’t working or seems to be
making things worse, taper off and re-think the problem.
Avoid unnecessary polypharmacy.

Remember that problems are rarely solved by
medications alone.
May 5, 2012
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Treatment of Psychiatric Disorders
 Anxiety
and Depression.
 Hyperactivity, Impulsivity, & Inattention.
 Repetitive behaviors.
 Aggression, self-injurious behavior and
“irritability.”
 Sleep.
May 5, 2012
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Anxiety Disorders

Higher rates than typically developing children.

May be provoked by changes in routine, new
social situations, too difficult task demands, etc.

May present as fearfulness, agitation, irritability,
tantrums, self-injurious behavior, aggression or
unusual fears, obsessive questioning, insistence
on sameness, stereotypical movements.
(Loveland, 2005)
May 5, 2012
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
In the higher-functioning adolescent, may be
provoked by realization that he doesn’t fit in and
present with exhaustion as he struggles to do
so.

Others may be in a constant state of
physiological arousal.
(Arick, 2005)
May 5, 2012
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“was like a constant feeling of stage fright….Just
imagine how you felt when you did something
really anxiety provoking, such as your first public
speaking engagement. Now imagine if you felt
that way most of the time for no reason….It was
like my brain was running at 200 miles an hour
instead of 60 miles an hour.”
(Grandin, 1992)
May 5, 2012
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Depression

Especially common in adolescence and among
higher functioning.

Provoked by being different, increasing
academic and social demands.

May present as decreased desire for social
interaction, irritability, increased insistence on
routines, disorganization, and inattention, and
exhaustion trying to fit in.
(Loveland, 2005)
May 5, 2012
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Treatment: Therapy

Little research on therapy for anxiety or
depression in children with ASD.

Always consider evidence-based therapy for
typically children, but modified to a child’s
developmental level.

For anxiety and depression, Cognitive Behavior
Therapy has the best support.
May 5, 2012
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Treatment: Medications

SSRI’s: limited studies to date, and not targeted to mood
disorders.

May have increased rates of SSRI-activation:


hyperactivity, restlessness, agitation, elation, irritability,
and insomnia,
especially in the young and at higher doses.
(Scahill, Martin, 2005)

Thus, start very low, go slowly, and monitor response
carefully.
May 5, 2012
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Hyperactivity, Impulsivity, and
Inattention
 May
be present in 1/3 or more of children
with autism:

Screening of 487 non-clinical children
• @ 50% had difficulty concentrating, short attention
span.
• @ 40% were squirmy/wiggly/fidgety.
• @ 30-40% were overactive or had too much
energy.
(Lecavalier, 2006)
May 5, 2012
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Strategies to Improve Executive
Function


Simplify tasks into discrete, concrete steps.
Usual visual aids (pictures, schedules, check-off lists.)
Use hand’s on learning (see one, do one, repeat as
necessary.)
Prepare for transitions and new experiences.
Decrease distractions.
Decrease stressors.
Coordinate assignments.

Make sure challenges are a good match for abilities.





May 5, 2012
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Medication Options:
RUPP Study on Methylphenidate

Autism Network Research Units of Pediatric
Psychopharmacology (RUPP)

2005: randomized, double-blind, placebo-controlled
crossover trial of methylphenidate with 72 children with
Autism and ADHD symptoms.

Methylphenidate doses of 0.125, 0.250, and 0.500
mg/kg, given three times a day.
(RUPP, 2005)
May 5, 2012
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RUPP: Methylphenidate

Response in 49 % of children with inattention,
distractibility, hyperactivity, and impulsivity most improved.

Effect size small to medium in magnitude of response.

No improvement in irritability, lethargy, stereotypical
movements, or inappropriate speech. Social withdrawal
worsened with increased dose.

Adverse effects with discontinuation in 18% of children.

Side effects included irritability, insomnia, decreased
appetite, and emotional outbursts.
(RUPP, 2005)
May 5, 2012
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RUPP vs. MTA
(Multisite Multimodal Treatment Study of Children with ADHD)

Children:
 Response Rate:
 Discontinued:

72
49%
18%
289
70-80%
1.4%
(owing to adverse effect)

Effect Size:
 Placebo:
0.48-0.89 0.35-1.31
15.5%
12.5%
CONCLUSION: Less effect, more side-effects.
(RUPP, 2005)
May 5, 2012
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Repetitive Behaviors

Diverse behaviors, vary widely, but persist over time.

May be strongest predictor of whether an early diagnosis
of ASD continues over time.
(Richler, et al, 2007)

When interrupted, can trigger anxiety, meltdowns,
aggression, and self-injury.
(King, et al, 2009)

Characterized by:




Stereotyped and repetitive motor mannerisms.
Inflexibility regarding routines and rituals. Rigid patterns of thought or
behavior.
Preoccupation with restricted patterns of interest.
Preoccupation with parts of objects.
(DSM-IV- TR)
May 5, 2012
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Behavioral Approach to
Maladaptive Behaviors

Function Analysis of Behavior to better understand
behavior, modify triggers and reinforcements, track
response to interventions.

Educate patient and care-givers.

Address stressors.

Increase communication skills.

Increase coping skills.

Consider medications if warranted.
May 5, 2012
PAL Conference
Repetitive Behaviors: Medications

SSRI’s: some small studies support fluoxetine (Prozac)*,
sertraline (Zoloft)*, citalopram (Citalopram)*,
escitalopram (Lexapro.)*

However, more recent and robust trials of citalopram*
found no significant improvement and was associated
with adverse effects including hyperactivity, impulsivity,
insomnia, stereotypy, and diarrhea.

Preliminary data for fluoxetine (SOFIA trial) is also
negative.
(King et all, 2009; Soorya et al, 2008)
May 5, 2012
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
Risperidone (Risperdal)*:

101 children, double-blind placebo-controlled:
• Demonstrated significant improvement in obsessions,
repetitive behaviors, and anxiety.
• Side-effects include weight gain, fatigue, drowsiness.
• Mean dose: 1.8mg +/- 0.7mg/day

Other agents (clomipramine, depakote, oxytocin,
etc.)
(Soorya et al, 2008)
May 5, 2012
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Aggression, Self-Injurious
Behavior, and Tantrums

Risperidone:




Best-studied FDA-approved treatment for autism.
For children 5-16 years.
For irritability, aggression, self-injury, tantrums, and
mood swings.
RUPP study: double-blind, placebo-controlled, 101
children and adolescents with autism and significant
irritability (aggression, SIB, and tantrums.)
(Stigler, McDougle, 2008)
May 5, 2012
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RUPP: Risperidone

57% reduction on the ABC irritability scale vs. 14% on
placebo.

69% considered responders vs. 12% on placebo.

Mean dose of 1.8mg/day.

5.9 lbs wt gain compared to 1.8 lbs on placebo

Drooling more frequently reported, but no difference in
EPS and tardive dyskinesia.
(Stigler, McDougle, 2008)
May 5, 2012
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RUPP: Risperidone

Improvements also noted in stereotypy and
hyperactivity.

No statistically significant improvement in
inappropriate speech or social withdrawal.

In similar Canadian study (79 children, with high
ABC scores, mean dose 1.2mg/day),
improvement noted in all ABC domains.
(Stigler, McDougle, 2008)
May 5, 2012
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Follow-up Studies

Open label 16 week continuation with 63 responders
No increase in target symptoms and dose remained
stable.

Weight gain (total 6 months) 11.2 lbs.

Taper trial of 32 responders randomized to:



10/16 (62.5%) on placebo had significant worsening.
2/16 (12.5%) remaining on risperidone had significant
worsening.
May need treatment greater than 6 months
(Stigler, McDougle, 2008)
May 5, 2012
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Aripiprazole (Abilify)

Recently approved by the FDA for irritability
associated with autistic disorder as
demonstrated by tantrums, aggression, and/or
self-injurious behavior in children 6-17 years old.

However, data is not as robust as for
risperidone.

Approval based upon two 8-week double-blind
placebo-controlled studies with majority of
participants under 13 years old.
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PAL Conference
Aripiprazole Study 1:




N=98, aged 6-17, mean age 9.3 yo, doses of 2-15mg/day day.
Mean-dose at 8 weeks was 8.6mg/day. Children treated with
psychotropic medications had a wash out prior to treatment.
67% vs 16% placebo were very much or much improved.
However, mean ABC Irritability subscale was only slightly lower
after treatment than mininum entry criteria: Thus, expect persistent
symptoms.
Discontinuation owing to adverse effects: 10.6% vs 5.9% on
placebo.
• EPS (tremor, muscle rigidity or spasm, akathisia, hyperactivity, hypo or
hyperkinesias) 14.9% vs 8.0% on placebo.
• Weight gain of at least 7% (mean 2.0kg by 8th week.)
(Owen, Sikich, et al, 2009)
May 5, 2012
PAL Conference
Aripiprazole Study 2



N=218, aged 6-17, 3 fixed doses of 5, 10, or 15mg/day
with start at 2mg then increased by 5mg each week to
target fixed dose. Similar wash-out of all psychotropic
medications.
All arms demonstrated improvement, but only 5mg
dose separated from placebo (35%) which was higher
than prior study.
Adverse events:
• Experienced by 72.5% placebo vs 85.2-89.8%.
• Most common adverse effects leading to withdrawal were
sedation, drooling and tremor.
• Weight gain: 0.4kg for placebo vs 1.4-1.6kg for treatment arms.
(Marcus, Owen 2009)
May 5, 2012
PAL Conference
Other Antipsychotic Trials

Olanzapine (Zyprexa)*: small, open label:


Quetiepine (Seroquel)*: small, open label:


generally less response than Risperidone, bigger
weight gain.
Less response and less well-tolerated.
Ziprasidone (Geodon)*: small, open label:

Unclear response, possibly weight-neutral, potential
for QTc prolongation (FDA warning).
(Stigler, McDougle, 2008)
May 5, 2012
PAL Conference
Other agents

Clonidine (Catapres)*: Small (<10 patients), short (4-6
week) double-blind, placebo-controlled crossover
studies:


Guanfacine (Tenex)*: Larger (80 patients with PDD)
retrospective, mean dose 2.6mg/day:



Decrease variable target symptoms with side-effects of
hypotension and sedation.
23.8% deemed “much improved.”
Transient sedation most common adverse effect.
Mood stabilizers: not enough information.
(Stigler, McDougle, 2008)
May 5, 2012
PAL Conference
Sleep Problems

44-86% children with autism have sleep problems.

May be related to abnormalities GABA, serotonin, and melatonin.

Consider other causes (Obstructive Sleep Apnea, non-REM arousal
disorder (including night terrors, sleep-walking), REM disorders
(acting out dreams), rhythmic movement disorders (head banging)
during sleep-wake transitions.

Rule out seizures.

Consider medication side effects.

Pediatric Sleep Questionnaire.

Also consider sleep evaluation if appropriate and available.
(Johnson, Malow, 2008)
May 5, 2012
PAL Conference
Treatment of Insomnia
 Sleep






hygiene remains key:
Maintain a schedule.
Avoid naps.
Avoid interruptions.
Consider a bedtime routine.
Decrease stimulation.
Avoid caffeine and other stimulants.
May 5, 2012
PAL Conference
Melatonin* in ASD

Melatonin*:


1 large retrospective study (100 children with Autism) with 85% reported
improved sleep and minimal side-effects.
Multiple small studies in autism & neurodevelopmental disabilities:
•
•
•
•
Reduced sleep latency
Improved sleep duration
Improved sleep efficiency (time in bed).
Minimal adverse effects except in refractory seizure disorders.
(Johnson, Malow, 2008)


Physiological doses (<500 micrograms) effective in shifting sleep
phase.
Hypnotic doses more typically used:




Start at 1mg and increase by 1mg q 2 weeks.
Maximum is generally 3mg, although doses to 6mg may be warranted.
Formulations may vary in bioavailability
Attempt to discontinue 6 or more weeks of good sleep.
(Johnson, Malow, 2008)
May 5, 2012
PAL Conference
References
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
American Psychiatric Association, (2000). Diagnostic and Statistical Manual of Mental Disorders, Text Revision,
4th edition. American Psychiatric Association, Washington, DC.
Arick, J. R., Krug, D. A. Fulllerton, A. et al. (2005). School-based programs. In Volkmar, F. R., Klin, A., Cohen, D.
(Eds.). Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed., pp 1003-1028.
Baranek, G. T., Parham, L. D., Bodfish, J. W. (2005). Sensory and motor features in autism: assessment and
intervention. In Volkmar, F. R., Klin, A., Cohen, D. (Eds.). Handbook of Autism and Pervasive Developmental
Disorders. Wiley, Hoboken, 3rd ed., pp 831-857.
Faja, S., Dawson, G. (2006). Early intervention for autism. In Luby, J. (Ed.). Handbook of Preschool Mental
Health: Development, Disorders, and Treatment. Guilford, New York, pp. 338-416.
Filipek, P. A. (2005). Medical aspects of autism. In Volkmar, F. R., Klin, A., Cohen, D. (Eds.). Handbook of
Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3rd ed., pp 534-578.
Frith, U. (2003). Autism: Explaining the Enigma, 2nd ed. Malden: Blackwell.
Frombonne, E. (2005). Epidemiological studies of pervasive developmental disorders. In Volkmar, F. R., Klin, A.,
Cohen, D. (Eds.). Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed., pp 4269.
Gerhardt, P. F., Holmes, D. L., (2005). Employment: options and issues for adolescents and adults with autism
spectrum disorders. In Volkmar, F. R., Klin, A., Cohen, D. (Eds.). Handbook of Autism and Pervasive
Developmental Disorders. Wiley, Hoboken, 3rd ed., pp 1087-1101.
Grandin, T. (1992). An inside view of autism. In Schopler, E. and Mesibov, G. B. (Eds.) High functioning
individuals with autism, pp 105-126.
Happe, F. (2005). The weak central coherence account of autism. In Volkmar, F. R., Klin, A., Cohen, D. (Eds.).
Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3rd ed., pp 640-649.
Howlin, P. (2005). Outcomes in autism spectrum disorders. In Volkmar, F. R., Klin, A., Cohen, D. (Eds.).
Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3rd ed., pp. 210-220.
Hussain, J., Woolf, A. D., Sandel, M., Shannon, (2007). Environmental evaluation of a child with developmental
disability. Pediatric Clinics of North America, 15(1): 47-62.
Johnson, K. P., Malow, B. A. (2008). Assessment and pharmacologic treatment of sleep disturbance in autism.
Child and Adolescent Psychiatric Clinics of North America, 17 (4): 773-785.
May 5, 2012
PAL Conference











Johnson C., Myers S., the Council on Children with Disabilities. (2007) Identification and evaluation of children
with autism spectrum disorders. Pediatrics, 120(5) 1183-1215.
Kim, Y. S., Leventhal, B. L., Koh, Y., Frombonne, E., Laska, E., Lim, E., Cheon, K., Kim, S., Kim, Y., Lee, H.,
Song, D., Grinker, R. R. (2011). Prevalence of Autism Spectrum Disorders in a Total Population Sample.
American Journal of Psychiatry in Advance, AiA:1-9.
King, B. H., Hollander, E., Sikich L., et al. (2009). Lack of efficacy of citalopram in children with autism spectrum
disorders and high levels of repetitive behavior. Archives of General Psychiatry, 66(6): 583-590.
Lacavalier, L. (2006). Behavior and emotional problems in young people with pervasive developmental disorders:
relative prevalence, effects of subject characteristics, and empirical classification. Journal of Autism and
Developmental Disorders, 36: 1101-1114.
Lord, C., Corsello, C. (2005). Diagnostic Instruments in Autistic Spectrum Disorders. In Volkmar, F. R., Klin, A.,
Cohen, D. (Eds.), Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed., pp 730771.
Loveland, K. A., Tunali-Kotoski, B. (2005) The school-age child with autism spectrum disorders. In Volkmar, F. R.,
Klin, A., Cohen, D. (Eds.), Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed.,
pp 247-287.
Minshew, A. N., Sweeney, J. A., Bauman, M. L., Webb, S. J. (2005). Neurological aspects of autism. In Volkmar,
F. R., Klin, A., Cohen, D. (Eds.), Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken,
3rd ed., pp 473-514.
Mundy, P., Burnette C. (2005). Joint attention and neurodevelopmental models of attention. In Volkmar, F. R.,
Klin, A., Cohen, D. (Eds.), Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3rd ed.,
pp 650-681.
Myers, S., Johnson, C., the Council on Children with Disabilities. (2007). Management of Children with Autism
Spectrum Disorders. Pediatrics, 120(5): 1162-1182.
Marcus, R. N., Owen R., Kamen, L., et al (2009). A Placebo-controlled, fixed-dose study of apriprazole in children
and adolescents with irritability associated with autistic disorder. Journal of the American Academy of Child and
Adolescent Psychiatry, 48:11, 1110-1119.
Owen, R., Sikich, L, Marcus, R. N., et al (2009). Aripiprazole in the treatment of irritability in children and
adolescents with autistic disorder. Pediatrics, 124(6), 1533-1540.
May 5, 2012
PAL Conference









Research Units of Pediatric Psychopharmacology (RUPP) Autism Network. (2005). Randomized, Controlled,
Crossover Trial of Methylphenidate in Pervasive Developmental Disorders with Hyperactivity. Archives of General
Psychiatry, 62: 1266-1274.
Richler, J, . Bishop, S. L., Kleinke, J. R., Lord, C., (2007), Restricted and repetitive behaviors in young children
with autism spectrum disorders. Journal of Autism and Developmental Disorders, 37 (1): 73-85.
Scahill, L. and Martin, A., (2005). Psychopharmacology, In Volkmar, F. R., Paul, R., Klin, A., Cohen, D. (Eds.)
Handbook of autism and pervasive developmental disorders. 3 rd ed., pp 1102-1117. Schreibman, L., and Ingersoll,
B. (2005). Behavioral interventions to promote learning in individuals with autism. In Volkmar, F. R., Klin, A.,
Cohen, D. (Eds.) Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed., pp. 882896.
Schreibman, L., Ingersoll, B., (2005). In Volkmar, F. R., Klin, A., Cohen, D. (Eds.) Handbook of Autism and
Pervasive Developmental Disorders. Wiley, Hoboken, 3rd ed., pp. 882-896.
Shea, V., and Mesibov, G. B., (2005). Adolescents and adults with autism. In Volkmar, F. R., Klin, A., Cohen, D.
(Eds.) Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed., pp. 288-311.
Soorya, L., Kiarashi, J., Hollander, E. (2008). Psychopharmacologic interventions for repetitive behaviors in autism
spectrum disorders. Child and Adolescent Psychiatric Clinics of North America, 17: 753-771.
Stigler, K. A., McDougle, C. J., (2008), Pharmacotherapy of irritability in pervasive developmental disorders. Child
and Adolescent Psychiatric Clinics of North America, 17: 739-752.
Volkmar, F. R., Klin, A. (2005). Issues in the classification of autism and related conditions. In Volkmar, F. R.,
Klin, A., Cohen, D. (Eds.) Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed.,
pp. 5-41.
Zwaigenbaum, L., Bryson, S., Rogers, S., et al. (2005). Behavioral manifestations of autism in the first year of life.
International Journal of Developmental Neuroscience, 23: 143-152.
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PAL Conference