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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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Presentation on theme: "An Approach to the Child with an Autism Spectrum Disorder A. A. Golombek, MD Attending, Seattle Children’s Hospital Consulting Psychiatrist, PAL Program."— Presentation transcript:

1 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, 2012PAL Conference

2 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, 2012PAL Conference

3 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. May 5, 2012PAL Conference

4  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) May 5, 2012PAL Conference

5 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) May 5, 2012PAL Conference

6 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) May 5, 2012PAL Conference

7 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) May 5, 2012PAL Conference

8 Prevalence  Increasing from 4.7/10,000 from 1966 to 1993 to 12.7/10,000 from 1994 to (Frombonne, 2005)  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.) (Frombonne, 2005) (Frombonne, 2005) May 5, 2012PAL Conference

9 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. (Hussain, 2007) May 5, 2012PAL Conference

10 When to Screen  Per the American Academy of Pediatrics: During well child checkups, especially at 18 or 24 months. 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 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. If there is a sibling with autism, which greatly increases the risk. (Johnson, 2007) May 5, 2012PAL Conference

11 Screening 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 play with them? 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 orient to his or her name by 1 year? Does he or she point to things or bring things to share? Does he or she point to things or bring things to share? (Zwaigenbaum, 2005) May 5, 2012PAL Conference

12 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 May 5, 2012PAL Conference

13 Diagnosing Autism  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 months: Modified Checklist for Autism in Toddlers (M-CHAT), 5-10 minute parent questionnaire, Sens/Spec: 0.85/0.93, at (Search “M-CHAT” then “Scoring M-CHAT”16-18 months: Modified Checklist for Autism in Toddlers (M-CHAT), 5-10 minute parent questionnaire, Sens/Spec: 0.85/0.93, at (Search “M-CHAT” then “Scoring M-CHAT”www.firstsigns.org 4-11 years: The Childhood Autism Spectrum Test (CAST), 10 minute parent questionnaire, Sens/Spec: 0.88/0.97, at years: The Childhood Autism Spectrum Test (CAST), 10 minute parent questionnaire, Sens/Spec: 0.88/0.97, at years: The Adolescent Autism Spectrum Quotient (AQ), 15 minute parent questionnaire, Sens/Spec: 0.89/1.0, at years: The Adolescent Autism Spectrum Quotient (AQ), 15 minute parent questionnaire, Sens/Spec: 0.89/1.0, at (Johnson, 2007)  In Autism centers: Autism Diagnostic Interview-Revised and Observation Scale (ADI-R, ADOS) may be used. 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.Especially helpful for children who are less than 2 years old or have intellectual disabilities. May 5, 2012PAL Conference

14 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. Apparently normal prenatal, head circumference, psychomotor development 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 movements (hand-wringing or hand-washing). Loss of purposeful hand skills and development of stereotyped hand 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: 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, play, bowel or bladder control, or motor skills (2 or more sx.) 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) Impairments in social interactions, language, and repetitive interests or behavior (2 or more sx.) (DSM-IV-TR, 2000) May 5, 2012PAL Conference

15 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) May 5, 2012PAL Conference

16 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) May 5, 2012PAL Conference

17 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) May 5, 2012PAL Conference

18 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) May 5, 2012PAL Conference

19 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) (DSM-IV-TR, 2000) May 5, 2012PAL Conference

20 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: Education Network: ( )http://www.npen.net ( )http://www.npen.net Information Calendar: Information Calendar: ( )http://www.wpic.org ( )http://www.wpic.org May 5, 2012PAL Conference

21 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) May 5, 2012PAL Conference

22 Applied Behavioral Analysis (ABA)  Skills learned through Prompting, shaping, reinforcement, and repetition. Prompting, shaping, reinforcement, and repetition. Emphasis on functional routines Emphasis on functional routines taught by breaking tasks down into simple and discrete steps,taught by breaking tasks down into simple and discrete steps, then “chaining” them together.then “chaining” them together. (Arick et al, 2005)  Most successful programs draw from this approach. May 5, 2012PAL Conference

23 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, 2012PAL Conference

24 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, 2012PAL Conference

25 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, 2012PAL Conference

26 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, 2012PAL Conference

27 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, 2012PAL Conference

28 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. Federal law mandates assistance with transition planning. May start at as early as 14 year old, but no later than 16. (Gerhardt, 2005) May start at as early as 14 year old, but no later than 16. (Gerhardt, 2005) May 5, 2012PAL Conference

29 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. Sensitive to noise? Consider ear muffs or access to a quiet room. Scratchy tag? Remove it Scratchy tag? Remove it Problematic behaviors (chewing, scratching self)? Consider a substitute activity and try to determine what triggers and reinforces the behavior. Problematic behaviors (chewing, scratching self)? Consider a substitute activity and try to determine what triggers and reinforces the behavior. May 5, 2012PAL Conference

30 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. Celiac antibodies, allergies to gluten, casein, molds; vitamin and trace element analysis, and intestinal permeability studies or stool analysis. (Filipek, 2005) May 5, 2012PAL Conference

31 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, 2012PAL Conference

32 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, 2012PAL Conference

33 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 eye- contact, flat affect, social withdrawal, impoverished or concrete thought, unusual movements, and repetitive behavior. (Howlin, 2005) May 5, 2012PAL Conference

34 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.) 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, 2012PAL Conference

35 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, 2012PAL Conference

36 Functional Analysis 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 functional. 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 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. Establish baseline.  Identify triggers and reinforcements. May 5, 2012PAL Conference

37 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, 2012PAL Conference

38 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, 2012PAL Conference

39 Medication  No medication to target core deficits of autism.  Limited data.  Differences in response: Expect decreased efficacy. Expect decreased efficacy. Expect increased adverse effects (agitation, irritability, aggression, disinhibition, dystonias, dyskinesias, etc.) 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, 2012PAL Conference

40 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, 2012PAL Conference

41 Treatment of Psychiatric Disorders  Anxiety and Depression.  Hyperactivity, Impulsivity, & Inattention.  Repetitive behaviors.  Aggression, self-injurious behavior and “irritability.”  Sleep. May 5, 2012PAL Conference

42 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, 2012PAL Conference

43  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, 2012PAL Conference

44 “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.” “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, 2012PAL Conference

45 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, 2012PAL Conference

46 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, 2012PAL Conference

47 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, hyperactivity, restlessness, agitation, elation, irritability, and insomnia, especially in the young and at higher doses. especially in the young and at higher doses. (Scahill, Martin, 2005)  Thus, start very low, go slowly, and monitor response carefully. May 5, 2012PAL Conference

48 Hyperactivity, Impulsivity, and Inattention  May be present in 1/3 or more of children with autism: Screening of 487 non-clinical children Screening of 487 non-clinical 50% had difficulty concentrating, short attention 50% had difficulty concentrating, short attention 40% were 40% were 30-40% were overactive or had too much energy. (Lecavalier, 30-40% were overactive or had too much energy. (Lecavalier, 2006) May 5, 2012PAL Conference

49 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, 2012PAL Conference

50 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 mg/kg, given three times a day. (RUPP, 2005) May 5, 2012PAL Conference

51 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, 2012PAL Conference

52 RUPP vs. MTA (Multisite Multimodal Treatment Study of Children with ADHD)  Children:72289  Response Rate:49%70-80%  Discontinued:18%1.4% (owing to adverse effect) (owing to adverse effect)  Effect Size:  Placebo:15.5%12.5% CONCLUSION: Less effect, more side-effects. (RUPP, 2005) May 5, 2012PAL Conference

53 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. Stereotyped and repetitive motor mannerisms. Inflexibility regarding routines and rituals. Rigid patterns of thought or behavior. Inflexibility regarding routines and rituals. Rigid patterns of thought or behavior. Preoccupation with restricted patterns of interest. Preoccupation with restricted patterns of interest. Preoccupation with parts of objects. Preoccupation with parts of objects. (DSM-IV- TR) May 5, 2012PAL Conference

54 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, 2012PAL Conference

55 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, 2012PAL Conference

56  Risperidone (Risperdal)*: 101 children, double-blind placebo-controlled: 101 children, double-blind placebo-controlled: Demonstrated significant improvement in obsessions, repetitive behaviors, and anxiety.Demonstrated significant improvement in obsessions, 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, etc.) (Soorya et al, 2008) May 5, 2012PAL Conference

57 Aggression, Self-Injurious Behavior, and Tantrums  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 mood swings. 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, 2012PAL Conference

58 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, 2012PAL Conference

59 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, 2012PAL Conference

60 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. 10/16 (62.5%) on placebo had significant worsening. 2/16 (12.5%) remaining on risperidone had significant worsening. 2/16 (12.5%) remaining on risperidone had significant worsening. May need treatment greater than 6 months May need treatment greater than 6 months (Stigler, McDougle, 2008) May 5, 2012PAL Conference

61 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. May 5, 2012PAL Conference

62 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. 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. 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. 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. 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.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 8 th week.)Weight gain of at least 7% (mean 2.0kg by 8 th week.) (Owen, Sikich, et al, 2009) May 5, 2012PAL Conference

63 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. 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. All arms demonstrated improvement, but only 5mg dose separated from placebo (35%) which was higher than prior study. Adverse events: Adverse events: Experienced by 72.5% placebo vs %.Experienced by 72.5% placebo vs %. Most common adverse effects leading to withdrawal were sedation, drooling and tremor.Most common adverse effects leading to withdrawal were sedation, drooling and tremor. Weight gain: 0.4kg for placebo vs kg for treatment arms.Weight gain: 0.4kg for placebo vs kg for treatment arms. (Marcus, Owen 2009) May 5, 2012PAL Conference

64 Other Antipsychotic Trials  Olanzapine (Zyprexa)*: small, open label: generally less response than Risperidone, bigger weight gain. generally less response than Risperidone, bigger weight gain.  Quetiepine (Seroquel)*: small, open label: Less response and less well-tolerated. Less response and less well-tolerated.  Ziprasidone (Geodon)*: small, open label: Unclear response, possibly weight-neutral, potential for QTc prolongation (FDA warning). Unclear response, possibly weight-neutral, potential for QTc prolongation (FDA warning). (Stigler, McDougle, 2008) May 5, 2012PAL Conference

65 Other agents  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. 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.” 23.8% deemed “much improved.” Transient sedation most common adverse effect. Transient sedation most common adverse effect.  Mood stabilizers: not enough information. (Stigler, McDougle, 2008) May 5, 2012PAL Conference

66 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. Rule out seizures. Consider medication side effects. Consider medication side effects.  Pediatric Sleep Questionnaire. Also consider sleep evaluation if appropriate and available. Also consider sleep evaluation if appropriate and available. (Johnson, Malow, 2008) May 5, 2012PAL Conference

67 Treatment of Insomnia  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. May 5, 2012PAL Conference

68 Melatonin* in ASD  Melatonin*: 1 large retrospective study (100 children with Autism) with 85% reported improved sleep and minimal side-effects. 1 large retrospective study (100 children with Autism) with 85% reported 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 except in refractory seizure disorders. (Johnson, Malow, 2008)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. 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 bioavailability Formulations 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) May 5, 2012PAL Conference

69 References  American Psychiatric Association, (2000). Diagnostic and Statistical Manual of Mental Disorders, Text Revision, 4 th 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  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, 3 rd ed., pp  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  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, 3 rd ed., pp  Frith, U. (2003). Autism: Explaining the Enigma, 2 nd 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  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  Grandin, T. (1992). An inside view of autism. In Schopler, E. and Mesibov, G. B. (Eds.) High functioning individuals with autism, pp  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  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  Hussain, J., Woolf, A. D., Sandel, M., Shannon, (2007). Environmental evaluation of a child with developmental disability. Pediatric Clinics of North America, 15(1):  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): May 5, 2012PAL Conference

70  Johnson C., Myers S., the Council on Children with Disabilities. (2007) Identification and evaluation of children with autism spectrum disorders. Pediatrics, 120(5)  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):  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:  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  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  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  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  Myers, S., Johnson, C., the Council on Children with Disabilities. (2007). Management of Children with Autism Spectrum Disorders. Pediatrics, 120(5):  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,  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), May 5, 2012PAL Conference

71  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:  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):  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 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  Schreibman, L., Ingersoll, B., (2005). In Volkmar, F. R., Klin, A., Cohen, D. (Eds.) Handbook of Autism and Pervasive Developmental Disorders. Wiley, Hoboken, 3 rd ed., pp  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  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:  Stigler, K. A., McDougle, C. J., (2008), Pharmacotherapy of irritability in pervasive developmental disorders. Child and Adolescent Psychiatric Clinics of North America, 17:  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  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: May 5, 2012PAL Conference


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