An Approach to the Child with an Autism Spectrum Disorder. A. A. Golombek, MD Attending, Seattle Children’s Hospital Consulting Psychiatrist, PAL Program. Disclosures. This talk includes the presentation of off-label medications indicated by an asterisk (*)
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A. A. Golombek, MD
Attending, Seattle Children’s Hospital
Consulting Psychiatrist, PAL Program
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.
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.
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)
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.
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.
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)
Increasing from 4.7/10,000 from 1966 to 1993 to 12.7/10,000 from 1994 to 2000.
As high as 2.64% in a recent population-based sample. (Kim, et al, 2011)
Some of increase likely due to increased awareness and broader phenotype (from which most of increase arises.)
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.(Hussain, 2007)
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?
Communication and Socialization Deficits
Cognition, including Executive Function
Adaptive Function and Readiness for the Future
Sensory and Motor Abnormalities
Medical and Neurological Illness
In the primary care system:
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
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.
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)
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.
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.
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.
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)
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.
Wyoming Department of Developmental Disabilities (http://wdh.state.wy.us/DDD/index.html)
Wyoming Parent Information Resource (PIRC) for assistance raising children with disabilities:
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)
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.
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.)
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.
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.
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.
Consider assessment for ADHD symptoms and treatment if warranted.
Challenges should be a good match for abilities.
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)
Most individuals with autism do not live independently as adults, but live with family or in supportive environments.
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.
Federal law mandates assistance with transition planning.
May start at as early as 14 year old, but no later than 16. (Gerhardt, 2005)
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.
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.
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.
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)
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.
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 eye-contact, flat affect, social withdrawal, impoverished or concrete thought, unusual movements, and repetitive behavior. (Howlin, 2005)
Disinhibition, akathisia, agitation, confusion, dystonias or dyskinesias, new-onset or increased seizures (remember that many psychotropic medications lower the seizure threshold.)
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 coping skills.
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.
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.
No medication to target core deficits of autism.
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.
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.
Anxiety and Depression.
Hyperactivity, Impulsivity, & Inattention.
Aggression, self-injurious behavior and “irritability.”
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)
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.
“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.”
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.
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 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)
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)
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)
Children: 72 289
Response Rate: 49% 70-80%
Discontinued: 18% 1.4%
(owing to adverse effect)
Effect Size: 0.48-0.89 0.35-1.31
Placebo: 15.5% 12.5%
CONCLUSION: Less effect, more side-effects.
(Richler, et al, 2007)
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)
Risperidone (Risperdal)*: 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.”
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)
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)
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)
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)
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)
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.
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)
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.
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)
Olanzapine (Zyprexa)*: small, open label:
generally less response than Risperidone, bigger weight gain.
Quetiepine (Seroquel)*: small, open label:
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)
Clonidine (Catapres)*: Small (<10 patients), short (4-6 week) double-blind, placebo-controlled crossover studies:
Decrease variable target symptoms with side-effects of hypotension and sedation.
Guanfacine (Tenex)*: Larger (80 patients with PDD) retrospective, mean dose 2.6mg/day:
23.8% deemed “much improved.”
Transient sedation most common adverse effect.
Mood stabilizers: not enough information.
(Stigler, McDougle, 2008)
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)
Sleep hygiene remains key:
Maintain a schedule.
Consider a bedtime routine.
Avoid caffeine and other stimulants.
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)