An Approach to the Child with an Autism Spectrum Disorder A. A. Golombek, MD Attending, Seattle Children’s Hospital Consulting Psychiatrist, PAL Program.

An Approach to the Child An Approach to the Child with an Autism Spectrum with an Autism Spectrum

DisorderDisorder

A. A. Golombek, MDA. A. Golombek, MD

Attending, Seattle Children’s HospitalAttending, Seattle Children’s Hospital

Consulting Psychiatrist, PAL ProgramConsulting Psychiatrist, PAL Program

May 5, 2012May 5, 2012 PAL ConferencePAL Conference

DisclosuresDisclosures

This talk includes the presentation of off-label This talk includes the presentation of off-label medications indicated by an asterisk (*)medications indicated by an asterisk (*)

This talk is designed for primary care providers. This talk is designed for primary care providers. It does not provide medical advice for individual It does not provide medical advice for individual patients and is not a substitute for care.patients and is not a substitute for care.

Financial disclosures: None.Financial disclosures: None.


Conceptual FoundationConceptual Foundation

Unusual group of children described by Unusual group of children described by Kanner in 1943:Kanner in 1943:

They lacked the ability or interest to “relate They lacked the ability or interest to “relate themselves in the ordinary way to people themselves in the ordinary way to people and situations.”and situations.” (Frith, 2003)(Frith, 2003)

Language was a struggle: they misused Language was a struggle: they misused pronouns, were excessively literal, limited pronouns, were excessively literal, limited to mimicry, or mute.to mimicry, or mute.


Change was a trial: they demonstrated an Change was a trial: they demonstrated an intense desire and need for sameness, whether intense desire and need for sameness, whether in behavior, interests, or events in a day. in behavior, interests, or events in a day.

They struggled to see the forest form the trees, They struggled to see the forest form the trees, “to experience wholes without full attention to “to experience wholes without full attention to constituent parts.” constituent parts.” (Happe, 2005)(Happe, 2005)

They reacted unusually to physical sensation, They reacted unusually to physical sensation, either too little or too much.either too little or too much.

(Volkmar, Klin, 2005)(Volkmar, Klin, 2005)


Theory of MindTheory of Mind

Realization that each person has individual Realization that each person has individual thoughts.thoughts.

Typically develops around the mental age of 5.Typically develops around the mental age of 5.

In children with autism, develops later or not at In children with autism, develops later or not at all.all.

Examined through tests of false belief.Examined through tests of false belief.(Frith, 2003)(Frith, 2003)


Theory of Weak Central CoherenceTheory of Weak Central Coherence

Understanding general concepts or principles is Understanding general concepts or principles is impaired.impaired.

Strength is in focus and memory of specific Strength is in focus and memory of specific situations.situations.

May be linked to executive functions.May be linked to executive functions.

Strongly influences learning styleStrongly influences learning style. . (Frith, 2003)(Frith, 2003)


Shared Joint AttentionShared Joint Attention

Impairments in ability of coordinating Impairments in ability of coordinating another’s attention with one’s one.another’s attention with one’s one.

Likely one of the foundations necessary Likely one of the foundations necessary for socialization, language formation, and for socialization, language formation, and learning. learning.

(Mundy, Burnette, (Mundy, Burnette, 2005)2005)


PrevalencePrevalence

Increasing from 4.7/10,000 from 1966 to Increasing from 4.7/10,000 from 1966 to 1993 to 12.7/10,000 from 1994 to 2000.1993 to 12.7/10,000 from 1994 to 2000.

(Frombonne, 2005)(Frombonne, 2005)

As high as 2.64% in a recent population-As high as 2.64% in a recent population-based sample.based sample. (Kim, et al, (Kim, et al, 2011)2011)

Some of increase likely due to increased Some of increase likely due to increased awareness and broader phenotype (from awareness and broader phenotype (from which most of increase arises.)which most of increase arises.)

(Frombonne, 2005)(Frombonne, 2005)


Causes of AutismCauses of Autism

Autism is heterogeneous disorder. Thus, it is unlikely Autism is heterogeneous disorder. Thus, it is unlikely that there will be a single cause or a single cure.that there will be a single cause or a single cure.

Possible contributors include genetic factors, Possible contributors include genetic factors,

neurotransmitters, metabolic disorders, and mitochondrial neurotransmitters, metabolic disorders, and mitochondrial abnormalities, among others.abnormalities, among others.

Evidence for a causal role for MMR vaccines or mercury Evidence for a causal role for MMR vaccines or mercury

levels is lacking.levels is lacking. (Hussain, 2007)(Hussain, 2007)


When to ScreenWhen to Screen

Per the American Academy of Pediatrics:Per the American Academy of Pediatrics: During well child checkups, especially at 18 or 24 During well child checkups, especially at 18 or 24

months.months.

If there is a concern by a parent, care-giver or If there is a concern by a parent, care-giver or pediatrician for social development or communication.pediatrician for social development or communication.

If there is a sibling with autism, which greatly If there is a sibling with autism, which greatly increases the risk.increases the risk.

(Johnson, 2007)(Johnson, 2007)


Screening QuestionsScreening Questions

Does child meet the gaze of others?Does child meet the gaze of others? Does her or she mimic expressions or smile socially?Does her or she mimic expressions or smile socially? Does child engage when parents talk to them or try to Does child engage when parents talk to them or try to

play with them?play with them? Does he or she orient to his or her name by 1 year?Does he or she orient to his or her name by 1 year? Does he or she point to things or bring things to Does he or she point to things or bring things to

share?share?

(Zwaigenbaum, 2005)(Zwaigenbaum, 2005)


Comprehensive AssessmentComprehensive Assessment AutismAutism

Communication and Socialization DeficitsCommunication and Socialization Deficits

Cognition, including Executive FunctionCognition, including Executive Function

Adaptive Function and Readiness for the FutureAdaptive Function and Readiness for the Future

Sensory and Motor AbnormalitiesSensory and Motor Abnormalities

Medical and Neurological IllnessMedical and Neurological Illness

Psychiatric ConcernsPsychiatric Concerns


Diagnosing AutismDiagnosing Autism

In the primary care system:In the primary care system: DSM criteria-IV-TR.DSM criteria-IV-TR. May supplement with a screening or assessment tool.May supplement with a screening or assessment tool.

• 16-18 months: Modified Checklist for Autism in Toddlers (M-CHAT), 5-10 16-18 months: Modified Checklist for Autism in Toddlers (M-CHAT), 5-10 minute parent questionnaire, Sens/Spec: 0.85/0.93, at minute parent questionnaire, Sens/Spec: 0.85/0.93, at www.firstsigns.org (Search “M-CHAT” then “Scoring M-CHAT”(Search “M-CHAT” then “Scoring M-CHAT”

• 4-11 years: The Childhood Autism Spectrum Test (CAST), 10 minute parent 4-11 years: The Childhood Autism Spectrum Test (CAST), 10 minute parent questionnaire, Sens/Spec: 0.88/0.97, at questionnaire, Sens/Spec: 0.88/0.97, at www.autismresearchcentre.com/tests

• 12-15 years: The Adolescent Autism Spectrum Quotient (AQ), 15 minute 12-15 years: The Adolescent Autism Spectrum Quotient (AQ), 15 minute parent questionnaire, Sens/Spec: 0.89/1.0, at parent questionnaire, Sens/Spec: 0.89/1.0, at www.autismresearchcentre.com/tests

(Johnson, 2007)(Johnson, 2007) In Autism centers:In Autism centers:

Autism Diagnostic Interview-Revised and Observation Scale (ADI-R, Autism Diagnostic Interview-Revised and Observation Scale (ADI-R, ADOS) may be used.ADOS) may be used.

• Especially helpful for children who are less than 2 years old or have Especially helpful for children who are less than 2 years old or have intellectual disabilities.intellectual disabilities.


From the DSM-IV-TR, 2000From the DSM-IV-TR, 2000 6 symptoms in impairments in social interactions, language 6 symptoms in impairments in social interactions, language

and repetitive interests or behavior.and repetitive interests or behavior.

Hallmark’s of Rett’s Disorder: Hallmark’s of Rett’s Disorder: Apparently normal prenatal, head circumference, psychomotor development Apparently normal prenatal, head circumference, psychomotor development

until 5 months of age.until 5 months of age. Deceleration of head growth between 5 and 48 months.Deceleration of head growth between 5 and 48 months. Loss of purposeful hand skills and development of stereotyped hand Loss of purposeful hand skills and development of stereotyped hand

movements (hand-wringing or hand-washing). movements (hand-wringing or hand-washing). Poorly coordinated gait and trunk movements. Poorly coordinated gait and trunk movements. Severely impaired language and severe psychomotor retardation.Severely impaired language and severe psychomotor retardation. Loss of social engagement.Loss of social engagement.

Hallmark’s of Child Disintegrative Disorder: Hallmark’s of Child Disintegrative Disorder: Apparent normal development until the age of 2 years.Apparent normal development until the age of 2 years. Loss of skills (before age 10) in language, social skills or adaptive function, 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.)play, bowel or bladder control, or motor skills (2 or more sx.) Impairments in social interactions, language, and repetitive interests or Impairments in social interactions, language, and repetitive interests or

behavior (2 or more sx.)behavior (2 or more sx.) (DSM-IV-TR, 2000)(DSM-IV-TR, 2000)


Qualitative Impairment in Social Qualitative Impairment in Social Interaction (at least 2 sx)Interaction (at least 2 sx)

1. Marked impairment in nonverbal behaviors (gaze, 1. Marked impairment in nonverbal behaviors (gaze, posture, expression.)posture, expression.)

2. Failure to develop peer relationships appropriate to 2. Failure to develop peer relationships appropriate to developmental level. developmental level.

3. Lack of spontaneous seeking to share enjoyment, 3. Lack of spontaneous seeking to share enjoyment, interests, or achievements with others (by pointing, interests, or achievements with others (by pointing, bringing, showing objects of interest.)bringing, showing objects of interest.)

4. Lack of social or emotional reciprocity.4. Lack of social or emotional reciprocity.(DSM-IV-TR, 2000)(DSM-IV-TR, 2000)


Qualitative Impairment in Qualitative Impairment in Communication (at least 1 sx)Communication (at least 1 sx)

1. Delay in or lack of development of spoken language 1. Delay in or lack of development of spoken language without compensation. without compensation.

2. Marked impairment in the ability to initiate or sustain 2. Marked impairment in the ability to initiate or sustain conversation.conversation.

3. Stereotyped, repetitive, or idiosyncratic use of language.3. Stereotyped, repetitive, or idiosyncratic use of language.

4. Lack of varied, spontaneous make-believe or social 4. Lack of varied, spontaneous make-believe or social imitative play appropriate to level.imitative play appropriate to level.

(DSM-IV-TR, 2000)(DSM-IV-TR, 2000)


Restricted, Repetitive, Stereotyped Restricted, Repetitive, Stereotyped Behavior, Interests, and Activities Behavior, Interests, and Activities

(at least 1 sx)(at least 1 sx)

1. encompassing preoccupation with stereotyped or restricted 1. encompassing preoccupation with stereotyped or restricted patterns of interest abnormal in intensity or focus.patterns of interest abnormal in intensity or focus.

2. Apparently inflexible adherence to specific, non-functioning 2. Apparently inflexible adherence to specific, non-functioning routines or rituals.routines or rituals.

3. Stereotyped and repetitive motor mannerisms (hand 3. Stereotyped and repetitive motor mannerisms (hand flapping.)flapping.)

4. Persistent preoccupation with parts of objects.4. Persistent preoccupation with parts of objects.(DSM-IV-TR, 2000)(DSM-IV-TR, 2000)


Asperger’s DisorderAsperger’s Disorder

Qualitative impairment in social interaction (at least 2 sx.)Qualitative impairment in social interaction (at least 2 sx.) Restricted, repetitive behaviors (at least 1 sx.)Restricted, repetitive behaviors (at least 1 sx.)

No delay in language (single words by 2, phrases by 3.)No delay in language (single words by 2, phrases by 3.)

No cognitive delays or delays in adaptive function.No cognitive delays or delays in adaptive function.

Still causes significant impairment in function.Still causes significant impairment in function. (DSM-IV-TR, 2000)(DSM-IV-TR, 2000)


Pervasive Developmental Disorder Pervasive Developmental Disorder (PDD) NOS(PDD) NOS

Severe and pervasive impairment in the development of Severe and pervasive impairment in the development of reciprocal social interaction associated with impairment reciprocal social interaction associated with impairment in verbal or nonverbal communication skills or the in verbal or nonverbal communication skills or the presence of stereotyped behaviors, interests, or presence of stereotyped behaviors, interests, or

activities.activities. (DSM-IV-TR, 2000)(DSM-IV-TR, 2000)


Wyoming ResourcesWyoming Resources

Wyoming Department of Developmental Wyoming Department of Developmental Disabilities (Disabilities (http://wdh.state.wy.us/DDD/index.html))

Wyoming Parent Information Resource (PIRC) Wyoming Parent Information Resource (PIRC) for assistance raising children with disabilities:for assistance raising children with disabilities:

Education Network:Education Network:• http://www.npen.net (307-684-7441) (307-684-7441)

Information Calendar: Information Calendar: • http://www.wpic.org (307-684-2277) (307-684-2277)


Treatment for AutismTreatment for Autism No medication to target core deficits.No medication to target core deficits.

No method of behavioral intervention with success > 50-70%.No method of behavioral intervention with success > 50-70%.(Schreibman, Ingersoll, 2005)(Schreibman, Ingersoll, 2005)

However, early and intense intervention has been shown to modify However, early and intense intervention has been shown to modify the course of autismthe course of autism (Faja, Dawson, 2006)(Faja, Dawson, 2006)

US National Research Council’s Principles for Effective Intervention: US National Research Council’s Principles for Effective Intervention: early; intense (25 hrs/wk); repeated, planned, brief sessions; 1:1 or early; intense (25 hrs/wk); repeated, planned, brief sessions; 1:1 or small group; parent involvement and training; and mechanisms to small group; parent involvement and training; and mechanisms to evaluate and modify progress.evaluate and modify progress. (Myers, 2007)(Myers, 2007)


Applied Behavioral Analysis (ABA)Applied Behavioral Analysis (ABA)

Skills learned throughSkills learned through Prompting, shaping, reinforcement, and repetition.Prompting, shaping, reinforcement, and repetition. Emphasis on functional routinesEmphasis on functional routines

• taught by breaking tasks down into simple and taught by breaking tasks down into simple and discrete steps, discrete steps,

• then “chaining” them together.then “chaining” them together.(Arick (Arick

et al, 2005)et al, 2005)

Most successful programs draw from this Most successful programs draw from this approach.approach.


Communication and SocializationCommunication and Socialization

Addressing deficits is key to improving function Addressing deficits is key to improving function and prognosis.and prognosis.

Always consider when addressing maladaptive Always consider when addressing maladaptive behavior.behavior.

Speech and Language evaluation (including Speech and Language evaluation (including expressive and receptive language, processing expressive and receptive language, processing speed, and for children with suspected ASD, speed, and for children with suspected ASD, social or pragmatic language skillssocial or pragmatic language skills.).)


Speech & Language InterventionsSpeech & Language Interventions For non-verbal children, Picture Exchange Communication System For non-verbal children, Picture Exchange Communication System

or sign language may help.or sign language may help.

Simplify language. Use short sentences. Avoid nuance, sarcasm, Simplify language. Use short sentences. Avoid nuance, sarcasm, double-meanings, non-verbal gestures. double-meanings, non-verbal gestures.

Pair verbal instructions with visual aides.Pair verbal instructions with visual aides.

Don’t confuse the child with affect: be calm and clear.Don’t confuse the child with affect: be calm and clear.

Social stories (cartoons that rehearse social situations.) Social stories (cartoons that rehearse social situations.)

Role-playing with concrete problem-solving (such as, “When I don’t Role-playing with concrete problem-solving (such as, “When I don’t want to do something, I will tell my teacher.)want to do something, I will tell my teacher.)

Social skills groups.Social skills groups.


Cognition and Executive FunctionCognition and Executive Function

In ASD prevalence of Intellectual Disability (ID) In ASD prevalence of Intellectual Disability (ID) ranges from 70-80% to 22-52%.ranges from 70-80% to 22-52%.

Intellectual ability is a strong predictor of Intellectual ability is a strong predictor of prognosisprognosis.. (Shea, Mesibov, 2005)(Shea, Mesibov, 2005)

Executive function skills are often impaired.Executive function skills are often impaired.


Strategies to Improve Executive Strategies to Improve Executive FunctionFunction

Simplify tasks into discrete, concrete steps.Simplify tasks into discrete, concrete steps. Usual visual aids (pictures, schedules, check-off lists.)Usual visual aids (pictures, schedules, check-off lists.) Use hand’s on learning (see one, do one, repeat as Use hand’s on learning (see one, do one, repeat as

necessary)necessary) Prepare for transitions and new experiences. Prepare for transitions and new experiences. Decrease distractions.Decrease distractions. Decrease stressors.Decrease stressors. Coordinate assignments.Coordinate assignments. Consider assessment for ADHD symptoms and Consider assessment for ADHD symptoms and

treatment if warranted.treatment if warranted.

Challenges should be a good match for abilities.Challenges should be a good match for abilities.


Adaptive FunctionAdaptive Function

Often lags behind cognitive function.Often lags behind cognitive function.

May facilitate additional services, especially if May facilitate additional services, especially if cognitive deficits are insufficient.cognitive deficits are insufficient.

Need to incorporate adaptive functions as goals Need to incorporate adaptive functions as goals of education.of education. (Lord, Corsello, 2005)(Lord, Corsello, 2005)


Adaptive Issues in LifeAdaptive Issues in Life

Most individuals with autism do not live independently as Most individuals with autism do not live independently as adults, but live with family or in supportive environments. adults, but live with family or in supportive environments.

(Howlin, 2005)(Howlin, 2005)

Up to 75% of adults with any disability are unemployed despite Up to 75% of adults with any disability are unemployed despite wanting to work, despite programs that demonstrate even very wanting to work, despite programs that demonstrate even very low functioning individuals can work.low functioning individuals can work.(Gerhardt, 2005)(Gerhardt, 2005)

Consider sheltered facilities, work coaches.Consider sheltered facilities, work coaches.

Educational Mandates: Educational Mandates: Federal law mandates assistance with transition planning.Federal law mandates assistance with transition planning. May start at as early as 14 year old, but no later than 16.May start at as early as 14 year old, but no later than 16.

(Gerhardt, 2005)(Gerhardt, 2005)


Sensory or Motor ProblemsSensory or Motor Problems Sensory sensitivities (or lack thereof) may provoke maladaptive Sensory sensitivities (or lack thereof) may provoke maladaptive

behaviors.behaviors.

Unfortunately, there is a paucity of evidence for methods that attempt to Unfortunately, there is a paucity of evidence for methods that attempt to

address primary deficitaddress primary deficit..(Baranek et al, 2005)(Baranek et al, 2005)

Consultation with an Occupational Therapist can help.Consultation with an Occupational Therapist can help.

Practical Solutions:Practical Solutions: Sensitive to noise? Consider ear muffs or access to a quiet room.Sensitive to noise? Consider ear muffs or access to a quiet room. Scratchy tag? Remove itScratchy tag? Remove it Problematic behaviors (chewing, scratching self)? Consider a Problematic behaviors (chewing, scratching self)? Consider a

substitute activity and try to determine what triggers and reinforces substitute activity and try to determine what triggers and reinforces the behavior.the behavior.


Medical EvaluationMedical Evaluation Guided by clinical presentation & symptoms including loss of skills, Guided by clinical presentation & symptoms including loss of skills,

focal neurological findings, family history, etc.focal neurological findings, family history, etc.

Check vision and hearing.Check vision and hearing.

Consider lead and Fragile X if Intellectual Disability is suspected.Consider lead and Fragile X if Intellectual Disability is suspected.

Ensure child receives normal medical care including dental care.Ensure child receives normal medical care including dental care.

Always assess for pain Always assess for pain (ear aches, dental pain, stomach aches,(ear aches, dental pain, stomach aches, etcetc) especially when there is a change in behavior.) especially when there is a change in behavior.

Gastrointestinal and sleep issues are commonGastrointestinal and sleep issues are common..

Not routinely recommend:Not routinely recommend: Celiac antibodies, allergies to gluten, casein, molds; vitamin Celiac antibodies, allergies to gluten, casein, molds; vitamin

and trace element analysis, and intestinal permeability studies and trace element analysis, and intestinal permeability studies or stool analysisor stool analysis..

(Filipek, 2005)(Filipek, 2005)May 5, 2012May 5, 2012 PAL ConferencePAL Conference

Neurological EvaluationNeurological Evaluation

Always consider if there is a loss of previously Always consider if there is a loss of previously acquired skillsacquired skills..

Consider EEG if seizures. Consider EEG if seizures.

Seizures are present in Seizures are present in 1/3 of individuals with autism.1/3 of individuals with autism.

Peak onset is before 5 years old and between 10 and 12 Peak onset is before 5 years old and between 10 and 12 years old.years old.

Function in ASD may improve significantly with treatment Function in ASD may improve significantly with treatment of seizures.of seizures. (Minshew et al, 2005)(Minshew et al, 2005)


Psychiatric Disorders Psychiatric Disorders in Children with ASDin Children with ASD

Paucity of systematic studies of incidence, but Paucity of systematic studies of incidence, but estimates range from 4-58%estimates range from 4-58%

Anxiety & Depression most common (up to 1/3)Anxiety & Depression most common (up to 1/3)

Similarly, deficits in executive function and Similarly, deficits in executive function and attention common.attention common.

No difference in prevalence of schizophrenia.No difference in prevalence of schizophrenia.(Howlin, 2005)(Howlin, 2005)


Diagnostic DifficultiesDiagnostic Difficulties

Under-reporting of symptoms in children whose Under-reporting of symptoms in children whose abilities to identify or communicate emotions, or abilities to identify or communicate emotions, or understand abstract concepts are compromised.understand abstract concepts are compromised.

Some symptoms of psychiatric disorders can Some symptoms of psychiatric disorders can also be seen with ASD including poor eye-also be seen with ASD including poor eye-contact, flat affect, social withdrawal, contact, flat affect, social withdrawal, impoverished or concrete thought, unusual impoverished or concrete thought, unusual movements, and repetitive behavior.movements, and repetitive behavior.

(Howlin, 2005)(Howlin, 2005)


Assessment: Rule out medical causes, Assessment: Rule out medical causes, especially if new-onsetespecially if new-onset

Pain.Pain. Medication side-effects:Medication side-effects:

Disinhibition, akathisia, agitation, confusion, Disinhibition, akathisia, agitation, confusion, dystonias or dyskinesias, new-onset or dystonias or dyskinesias, new-onset or increased seizures (remember that many increased seizures (remember that many psychotropic medications lower the seizure psychotropic medications lower the seizure threshold.)threshold.)

Drug-drug interactions.Drug-drug interactions. Seizures.Seizures.


Assessment: Consider StressorsAssessment: Consider Stressors

Changes in care-givers, home, school, routines, and Changes in care-givers, home, school, routines, and transitions.transitions.

Lack of support, teasing, bullying, neglect, and abuse.Lack of support, teasing, bullying, neglect, and abuse.

Environmental conditions: too noisy, too chaotic, too Environmental conditions: too noisy, too chaotic, too crowded, etc.crowded, etc.

Inappropriate task demands: too demanding vs. boring.Inappropriate task demands: too demanding vs. boring.

Inadequate communication.Inadequate communication.

Inadequate coping skills.Inadequate coping skills.


Functional Analysis of BehaviorFunctional Analysis of Behavior Causes of behavior:Causes of behavior:

If random, consider medical or neurological cause.If random, consider medical or neurological cause. If not random, it is likely an attempt to communicate or is somehow If not random, it is likely an attempt to communicate or is somehow

functional.functional.

Is the behavior an attempt to communicate? “I’m scared, mad, Is the behavior an attempt to communicate? “I’m scared, mad, frustrated, irritated, sad, or overwhelmed!”frustrated, irritated, sad, or overwhelmed!”

Does the behavior result in a gain?Does the behavior result in a gain? Getting something one wants? Attention, a toy, or a treat?Getting something one wants? Attention, a toy, or a treat? Getting out of a situation one finds unpleasant or overwhelming?Getting out of a situation one finds unpleasant or overwhelming?

Identify nature, timing, frequency, and duration of behavior. Identify nature, timing, frequency, and duration of behavior. Establish baseline.Establish baseline.

Identify triggers and reinforcements.Identify triggers and reinforcements.


Recommended Approach to Recommended Approach to TreatmentTreatment

When possible, identify a specific psychiatric When possible, identify a specific psychiatric diagnosis.diagnosis.

When not possible, identify specific target When not possible, identify specific target symptoms.symptoms.

Obtained informed consent from the patient if Obtained informed consent from the patient if they have capacity. If not, still provide they have capacity. If not, still provide developmentally appropriate explanations of developmentally appropriate explanations of risks, benefits, and alternatives.risks, benefits, and alternatives.


InterventionsInterventions Educate individuals and care-givers.Educate individuals and care-givers.

Address stressorsAddress stressors..

Increase communication skills.Increase communication skills.

Increase coping skills.Increase coping skills.

Behavior Therapy (modifying triggers and reinforcements)Behavior Therapy (modifying triggers and reinforcements)

Consider other evidence-based therapies as appropriate to Consider other evidence-based therapies as appropriate to disorder, symptom, and developmental abilities.disorder, symptom, and developmental abilities.

Consider medications in the context of the above interventions, but Consider medications in the context of the above interventions, but not as an isolated intervention.not as an isolated intervention.


MedicationMedication No medication to target core deficits of autism.No medication to target core deficits of autism.

Limited data.Limited data.

Differences in response:Differences in response: Expect decreased efficacy.Expect decreased efficacy. Expect increased adverse effects (agitation, irritability, Expect increased adverse effects (agitation, irritability,

aggression, disinhibition, dystonias, dyskinesias, etc.)aggression, disinhibition, dystonias, dyskinesias, etc.)

Start low and go slow, tracking response. Start low and go slow, tracking response.

Maximum doses Maximum doses less than or equalless than or equal to for the typically to for the typically developing.developing.


Avoid pitfallsAvoid pitfalls Track responses to intervention.Track responses to intervention.

Distinguish between a partial positive response and Distinguish between a partial positive response and tolerance to adverse effects.tolerance to adverse effects.

If a given intervention isn’t working or seems to be If a given intervention isn’t working or seems to be making things worse, taper off and re-think the problem. making things worse, taper off and re-think the problem. Avoid unnecessary polypharmacy. Avoid unnecessary polypharmacy.

Remember that problems are rarely solved by Remember that problems are rarely solved by medications alone.medications alone.


Treatment of Psychiatric DisordersTreatment of Psychiatric Disorders

Anxiety and Depression.Anxiety and Depression. Hyperactivity, Impulsivity, & Inattention.Hyperactivity, Impulsivity, & Inattention. Repetitive behaviors.Repetitive behaviors. Aggression, self-injurious behavior and Aggression, self-injurious behavior and

“irritability.”“irritability.” Sleep.Sleep.


Anxiety DisordersAnxiety Disorders

Higher rates than typically developing children.Higher rates than typically developing children.

May be provoked by changes in routine, new May be provoked by changes in routine, new social situations, too difficult task demands, etc.social situations, too difficult task demands, etc.

May present as fearfulness, agitation, irritability, May present as fearfulness, agitation, irritability, tantrums, self-injurious behavior, aggression or tantrums, self-injurious behavior, aggression or unusual fears, obsessive questioning, insistence unusual fears, obsessive questioning, insistence on sameness, stereotypical movements. on sameness, stereotypical movements.

(Loveland, 2005)(Loveland, 2005)


In the higher-functioning adolescent, may be In the higher-functioning adolescent, may be provoked by realization that he doesn’t fit in and provoked by realization that he doesn’t fit in and present with exhaustion as he struggles to do present with exhaustion as he struggles to do so.so.

Others may be in a constant state of Others may be in a constant state of physiological arousal.physiological arousal.

(Arick, (Arick,

2005)2005)


“ “was like a constant feeling of stage fright….Just was like a constant feeling of stage fright….Just imagine how you felt when you did something imagine how you felt when you did something really anxiety provoking, such as your first public really anxiety provoking, such as your first public speaking engagement. Now imagine if you felt speaking engagement. Now imagine if you felt that way most of the time for no reason….It was that way most of the time for no reason….It was like my brain was running at 200 miles an hour like my brain was running at 200 miles an hour instead of 60 miles an hour.”instead of 60 miles an hour.”

(Grandin, 1992)(Grandin, 1992)


DepressionDepression

Especially common in adolescence and among Especially common in adolescence and among higher functioning.higher functioning.

Provoked by being different, increasing academic Provoked by being different, increasing academic and social demands.and social demands.

May present as decreased desire for social May present as decreased desire for social interaction, irritability, increased insistence on interaction, irritability, increased insistence on routines, disorganization, and inattention, and routines, disorganization, and inattention, and exhaustion trying to fit in.exhaustion trying to fit in.

(Loveland, 2005)(Loveland, 2005)


Treatment: TherapyTreatment: Therapy

Little research on therapy for anxiety or Little research on therapy for anxiety or depression in children with ASD.depression in children with ASD.

Always consider evidence-based therapy for Always consider evidence-based therapy for typically children, but modified to a child’s typically children, but modified to a child’s developmental level.developmental level.

For anxiety and depression, Cognitive Behavior For anxiety and depression, Cognitive Behavior Therapy has the best support.Therapy has the best support.


Treatment: MedicationsTreatment: Medications

SSRI’s: limited studies to date, and not targeted to mood SSRI’s: limited studies to date, and not targeted to mood disorders. disorders.

May have increased rates of SSRI-activation:May have increased rates of SSRI-activation: hyperactivity, restlessness, agitation, elation, irritability, hyperactivity, restlessness, agitation, elation, irritability,

and insomnia, and insomnia, especially in the young and at higher doses.especially in the young and at higher doses.

(Scahill, Martin, 2005)(Scahill, Martin, 2005)

Thus, start very low, go slowly, and monitor response Thus, start very low, go slowly, and monitor response carefully.carefully.


Hyperactivity, Impulsivity, and Hyperactivity, Impulsivity, and InattentionInattention

May be present in 1/3 or more of children May be present in 1/3 or more of children with autism:with autism: Screening of 487 non-clinical childrenScreening of 487 non-clinical children

• @ 50% had difficulty concentrating, short attention @ 50% had difficulty concentrating, short attention span.span.

• @ 40% were squirmy/wiggly/fidgety.@ 40% were squirmy/wiggly/fidgety.• @ 30-40% were overactive or had too much @ 30-40% were overactive or had too much

energy.energy. (Lecavalier, 2006)(Lecavalier, 2006)


Strategies to Improve Executive Strategies to Improve Executive FunctionFunction

Simplify tasks into discrete, concrete steps.Simplify tasks into discrete, concrete steps. Usual visual aids (pictures, schedules, check-off lists.)Usual visual aids (pictures, schedules, check-off lists.) Use hand’s on learning (see one, do one, repeat as Use hand’s on learning (see one, do one, repeat as

necessary.)necessary.) Prepare for transitions and new experiences. Prepare for transitions and new experiences. Decrease distractions.Decrease distractions. Decrease stressors.Decrease stressors. Coordinate assignments.Coordinate assignments.

Make sure challenges are a good match for abilities.Make sure challenges are a good match for abilities.


Medication Options: Medication Options: RUPP Study on MethylphenidateRUPP Study on Methylphenidate

Autism Network Research Units of Pediatric Autism Network Research Units of Pediatric Psychopharmacology (RUPP)Psychopharmacology (RUPP)

2005: randomized, double-blind, placebo-controlled 2005: randomized, double-blind, placebo-controlled crossover trial of methylphenidate with 72 children with crossover trial of methylphenidate with 72 children with Autism and ADHD symptoms.Autism and ADHD symptoms.

Methylphenidate doses of 0.125, 0.250, and 0.500 Methylphenidate doses of 0.125, 0.250, and 0.500 mg/kg, given three times a day.mg/kg, given three times a day.

(RUPP, 2005)(RUPP, 2005)


RUPP: MethylphenidateRUPP: Methylphenidate Response in 49 % of children with inattention, Response in 49 % of children with inattention,

distractibility, hyperactivity, and impulsivity most improved.distractibility, hyperactivity, and impulsivity most improved.

Effect size small to medium in magnitude of response.Effect size small to medium in magnitude of response.

No improvement in irritability, lethargy, stereotypical No improvement in irritability, lethargy, stereotypical movements, or inappropriate speech. movements, or inappropriate speech. Social withdrawal Social withdrawal worsened with increased doseworsened with increased dose..

Adverse effects with discontinuation in 18% of children.Adverse effects with discontinuation in 18% of children.

Side effects included irritability, insomnia, decreased Side effects included irritability, insomnia, decreased appetite, and emotional outbursts.appetite, and emotional outbursts.

(RUPP, 2005)(RUPP, 2005)


RUPP vs. MTA RUPP vs. MTA (Multisite Multimodal Treatment Study of Children with ADHD)(Multisite Multimodal Treatment Study of Children with ADHD)

Children:Children: 7272 289289 Response Rate:Response Rate: 49%49% 70-80%70-80% Discontinued:Discontinued: 18%18% 1.4%1.4%

(owing to adverse effect)(owing to adverse effect)

Effect Size:Effect Size: 0.48-0.89 0.35-1.310.48-0.89 0.35-1.31 Placebo:Placebo: 15.5%15.5% 12.5%12.5%

CONCLUSION: Less effect, more side-effects.CONCLUSION: Less effect, more side-effects.(RUPP, 2005)(RUPP, 2005)


Repetitive BehaviorsRepetitive Behaviors Diverse behaviors, vary widely, but persist over time.Diverse behaviors, vary widely, but persist over time.

May be strongest predictor of whether an early diagnosis May be strongest predictor of whether an early diagnosis of ASD continues over time.of ASD continues over time.

(Richler, et al, 2007)(Richler, et al, 2007)

When interrupted, can trigger anxiety, meltdowns, When interrupted, can trigger anxiety, meltdowns, aggression, and self-injury.aggression, and self-injury. (King, et al, 2009)(King, et al, 2009)

Characterized by:Characterized by: Stereotyped and repetitive motor mannerisms.Stereotyped and repetitive motor mannerisms. Inflexibility regarding routines and rituals. Rigid patterns of thought or Inflexibility regarding routines and rituals. Rigid patterns of thought or

behavior.behavior. Preoccupation with restricted patterns of interest.Preoccupation with restricted patterns of interest. Preoccupation with parts of objects. Preoccupation with parts of objects.

(DSM-(DSM-IV- TR)IV- TR)


Behavioral Approach to Behavioral Approach to Maladaptive BehaviorsMaladaptive Behaviors

Function Analysis of Behavior to better understand Function Analysis of Behavior to better understand behavior, modify triggers and reinforcements, track behavior, modify triggers and reinforcements, track response to interventions.response to interventions.

Educate patient and care-givers.Educate patient and care-givers.

Address stressorsAddress stressors..

Increase communication skills.Increase communication skills.

Increase coping skills.Increase coping skills.

Consider medications if warranted. Consider medications if warranted.


Repetitive Behaviors: MedicationsRepetitive Behaviors: Medications

SSRI’s: some small studies support fluoxetine (Prozac)*, SSRI’s: some small studies support fluoxetine (Prozac)*, sertraline (Zoloft)*, citalopram (Citalopram)*, sertraline (Zoloft)*, citalopram (Citalopram)*, escitalopram (Lexapro.)*escitalopram (Lexapro.)*

However, more recent and robust trials of citalopram* However, more recent and robust trials of citalopram* found found nono significant improvement and was associated significant improvement and was associated with adverse effects including hyperactivity, impulsivity, with adverse effects including hyperactivity, impulsivity, insomnia, stereotypy, and diarrhea. insomnia, stereotypy, and diarrhea.

Preliminary data for fluoxetine (SOFIA trial) is also Preliminary data for fluoxetine (SOFIA trial) is also

negative. negative. (King (King

et all, 2009; Soorya et al, 2008)et all, 2009; Soorya et al, 2008)


Risperidone (Risperdal)*:Risperidone (Risperdal)*: 101 children, double-blind placebo-controlled:101 children, double-blind placebo-controlled:

• Demonstrated significant improvement in obsessions, Demonstrated significant improvement in obsessions, repetitive behaviors, and anxiety.repetitive behaviors, and anxiety.

• Side-effects include weight gain, fatigue, drowsiness.Side-effects include weight gain, fatigue, drowsiness.

• Mean dose: 1.8mg +/- 0.7mg/dayMean dose: 1.8mg +/- 0.7mg/day

Other agents (clomipramine, depakote, oxytocin, Other agents (clomipramine, depakote, oxytocin, etc.)etc.)

(Soorya et al, (Soorya et al, 2008)2008)


Aggression, Self-Injurious Aggression, Self-Injurious Behavior, and TantrumsBehavior, and Tantrums

Risperidone:Risperidone: Best-studied FDA-approved treatment for autism.Best-studied FDA-approved treatment for autism. For children 5-16 years.For children 5-16 years. For irritability, aggression, self-injury, tantrums, and For irritability, aggression, self-injury, tantrums, and

mood swings. mood swings.

RUPP study: double-blind, placebo-controlled, 101 RUPP study: double-blind, placebo-controlled, 101 children and adolescents with autism and significant children and adolescents with autism and significant irritability (aggression, SIB, and tantrums.)irritability (aggression, SIB, and tantrums.)

(Stigler, McDougle, 2008)(Stigler, McDougle, 2008)


RUPP: RisperidoneRUPP: Risperidone 57% reduction on the ABC irritability scale vs. 14% on 57% reduction on the ABC irritability scale vs. 14% on

placebo.placebo.

69% considered responders vs. 12% on placebo.69% considered responders vs. 12% on placebo.

Mean dose of 1.8mg/day.Mean dose of 1.8mg/day.

5.9 lbs wt gain compared to 1.8 lbs on placebo5.9 lbs wt gain compared to 1.8 lbs on placebo

Drooling more frequently reported, but no difference in Drooling more frequently reported, but no difference in EPS and tardive dyskinesia.EPS and tardive dyskinesia.

((Stigler, McDougle, 2008)Stigler, McDougle, 2008)May 5, 2012May 5, 2012 PAL ConferencePAL Conference

RUPP: RisperidoneRUPP: Risperidone

Improvements also noted in stereotypy and Improvements also noted in stereotypy and hyperactivity.hyperactivity.

No statistically significant improvement in No statistically significant improvement in inappropriate speech or social withdrawal.inappropriate speech or social withdrawal.

In similar Canadian study (79 children, with high In similar Canadian study (79 children, with high ABC scores, mean dose 1.2mg/day), ABC scores, mean dose 1.2mg/day), improvement noted in all ABC domains.improvement noted in all ABC domains.

(Stigler, McDougle, (Stigler, McDougle, 2008)2008)


Follow-up StudiesFollow-up Studies Open label 16 week continuation with 63 respondersOpen label 16 week continuation with 63 responders

No increase in target symptoms and dose remained No increase in target symptoms and dose remained stable.stable.

Weight gain (total 6 months) 11.2 lbs.Weight gain (total 6 months) 11.2 lbs.

Taper trial of 32 responders randomized to:Taper trial of 32 responders randomized to: 10/16 (62.5%) on placebo had significant worsening.10/16 (62.5%) on placebo had significant worsening. 2/16 (12.5%) remaining on risperidone had significant 2/16 (12.5%) remaining on risperidone had significant

worsening.worsening. May need treatment greater than 6 monthsMay need treatment greater than 6 months



Aripiprazole (Abilify)Aripiprazole (Abilify) Recently approved by the FDA for irritability Recently approved by the FDA for irritability

associated with autistic disorder as associated with autistic disorder as demonstrated by tantrums, aggression, and/or demonstrated by tantrums, aggression, and/or self-injurious behavior in children 6-17 years old.self-injurious behavior in children 6-17 years old.

However, data is not as robust as for However, data is not as robust as for

risperidone.risperidone.

Approval based upon two 8-week double-blind Approval based upon two 8-week double-blind placebo-controlled studies with majority of placebo-controlled studies with majority of participants under 13 years old.participants under 13 years old.


Aripiprazole Study 1:Aripiprazole Study 1: N=98, aged 6-17, mean age 9.3 yo, doses of 2-15mg/day day. 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 Mean-dose at 8 weeks was 8.6mg/day. Children treated with psychotropic medications had a wash out prior to treatment.psychotropic medications had a wash out prior to treatment.

67% vs 16% placebo were very much or much improved.67% vs 16% placebo were very much or much improved.

However, mean ABC Irritability subscale was only slightly lower However, mean ABC Irritability subscale was only slightly lower after treatment than mininum entry criteria: Thus, expect persistent after treatment than mininum entry criteria: Thus, expect persistent symptoms.symptoms.

Discontinuation owing to adverse effects: 10.6% vs 5.9% on Discontinuation owing to adverse effects: 10.6% vs 5.9% on placebo.placebo.

• EPS (tremor, muscle rigidity or spasm, akathisia, hyperactivity, hypo or EPS (tremor, muscle rigidity or spasm, akathisia, hyperactivity, hypo or hyperkinesias) 14.9% vs 8.0% on placebo.hyperkinesias) 14.9% vs 8.0% on placebo.

• Weight gain of at least 7% (mean 2.0kg by 8Weight gain of at least 7% (mean 2.0kg by 8thth week.) week.)(Owen, (Owen,

Sikich, et al, 2009)Sikich, et al, 2009)


Aripiprazole Study 2Aripiprazole Study 2 N=218, aged 6-17, 3 fixed doses of 5, 10, or 15mg/day 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 with start at 2mg then increased by 5mg each week to target fixed dose. Similar wash-out of all psychotropic target fixed dose. Similar wash-out of all psychotropic medications.medications.

All arms demonstrated improvement, but only 5mg All arms demonstrated improvement, but only 5mg dose separated from placebo (35%) which was higher dose separated from placebo (35%) which was higher than prior study.than prior study.

Adverse events:Adverse events:• Experienced by 72.5% placebo vs 85.2-89.8%.Experienced by 72.5% placebo vs 85.2-89.8%.• Most common adverse effects leading to withdrawal were Most common adverse effects leading to withdrawal were

sedation, drooling and tremor. sedation, drooling and tremor. • Weight gain: 0.4kg for placebo vs 1.4-1.6kg for treatment arms.Weight gain: 0.4kg for placebo vs 1.4-1.6kg for treatment arms.

(Marcus, (Marcus, Owen 2009)Owen 2009)


Other Antipsychotic TrialsOther Antipsychotic Trials

Olanzapine (Zyprexa)*: small, open label:Olanzapine (Zyprexa)*: small, open label: generally less response than Risperidone, bigger generally less response than Risperidone, bigger

weight gain.weight gain.

Quetiepine (Seroquel)*: small, open label: Quetiepine (Seroquel)*: small, open label: Less response and less well-tolerated.Less response and less well-tolerated.

Ziprasidone (Geodon)*: small, open label:Ziprasidone (Geodon)*: small, open label: Unclear response, possibly weight-neutral, potential Unclear response, possibly weight-neutral, potential

for QTc prolongation (FDA warning).for QTc prolongation (FDA warning).



Other agentsOther agents Clonidine (Catapres)*: Small (<10 patients), short (4-6 Clonidine (Catapres)*: Small (<10 patients), short (4-6

week) double-blind, placebo-controlled crossover week) double-blind, placebo-controlled crossover studies:studies: Decrease variable target symptoms with side-effects of Decrease variable target symptoms with side-effects of

hypotension and sedation.hypotension and sedation.

Guanfacine (Tenex)*: Larger (80 patients with PDD) Guanfacine (Tenex)*: Larger (80 patients with PDD) retrospective, mean dose 2.6mg/day:retrospective, mean dose 2.6mg/day: 23.8% deemed “much improved.”23.8% deemed “much improved.” Transient sedation most common adverse effect.Transient sedation most common adverse effect.

Mood stabilizers: not enough information.Mood stabilizers: not enough information.(Stigler, McDougle, (Stigler, McDougle,

2008)2008)


Sleep ProblemsSleep Problems

44-86% children with autism have sleep problems.44-86% children with autism have sleep problems.

May be related to abnormalities GABA, serotonin, and melatonin.May be related to abnormalities GABA, serotonin, and melatonin.

Consider other causes (Obstructive Sleep Apnea, non-REM arousal Consider other causes (Obstructive Sleep Apnea, non-REM arousal disorder (including night terrors, sleep-walking), REM disorders disorder (including night terrors, sleep-walking), REM disorders (acting out dreams), rhythmic movement disorders (head banging) (acting out dreams), rhythmic movement disorders (head banging) during sleep-wake transitions.during sleep-wake transitions.

Rule out seizures.Rule out seizures. Consider medication side effects.Consider medication side effects.

Pediatric Sleep Questionnaire.Pediatric Sleep Questionnaire. Also consider sleep evaluation if appropriate and available.Also consider sleep evaluation if appropriate and available.

(Johnson, Malow, 2008)(Johnson, Malow, 2008)


Treatment of InsomniaTreatment of Insomnia

Sleep hygiene remains key:Sleep hygiene remains key: Maintain a schedule.Maintain a schedule. Avoid naps.Avoid naps. Avoid interruptions.Avoid interruptions. Consider a bedtime routine.Consider a bedtime routine. Decrease stimulation.Decrease stimulation. Avoid caffeine and other stimulants.Avoid caffeine and other stimulants.


Melatonin* in ASDMelatonin* in ASD Melatonin*:Melatonin*:

1 large retrospective study (100 children with Autism) with 85% reported 1 large retrospective study (100 children with Autism) with 85% reported improved sleep and minimal side-effects.improved sleep and minimal side-effects.

Multiple small studies in autism & neurodevelopmental disabilities:Multiple small studies in autism & neurodevelopmental disabilities:• Reduced sleep latencyReduced sleep latency• Improved sleep durationImproved sleep duration• Improved sleep efficiency (time in bed).Improved sleep efficiency (time in bed).• Minimal adverse effects Minimal adverse effects except in refractory seizure disordersexcept in refractory seizure disorders..

(Johnson, Malow, (Johnson, Malow, 2008)2008)

Physiological doses (<500 micrograms) effective in shifting sleep Physiological doses (<500 micrograms) effective in shifting sleep phase.phase.

Hypnotic doses more typically used:Hypnotic doses more typically used: Start at 1mg and increase by 1mg q 2 weeks.Start at 1mg and increase by 1mg q 2 weeks. Maximum is generally 3mg, although doses to 6mg may be warranted.Maximum is generally 3mg, although doses to 6mg may be warranted. Formulations may vary in bioavailabilityFormulations may vary in bioavailability Attempt to discontinue 6 or more weeks of good sleep.Attempt to discontinue 6 or more weeks of good sleep.

(Johnson, Malow, 2008)(Johnson, Malow, 2008)


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An Approach to the Child with an Autism Spectrum Disorder A. A. Golombek, MD Attending, Seattle Children’s Hospital Consulting Psychiatrist, PAL Program.

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