Autism Spectrum Disorder: An Update Kathleen A. Koth, D.O.

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1 Autism Spectrum Disorder: An Update Kathleen A. Koth, D.O. Assistant Professor, Child and Adolescent Psychiatry Program Director, Child and Adolescent Psychiatry Fellowship President, Wisconsin Council of Child and Adolescent Psychiatry Member, Committee on Autism Spectrum Disorders and Intellectual Disabilities, American Academy of Child and Adolescent Psychiatry Disclosures Travel expenses from WIAPP/CPCP for this conference Objectives Discuss diagnostic changes in DSM V. Review current screening recommendations for ASD. Review current treatment recommendations for ASD. Review medication uses and limitations in ASD. Screening AAP recommends that all children be screened for ASD at 18 and 24 months along with regular developmental surveillance as part of the Bright Futures guidelines. For toddlers: CHAT KK1 M CHAT For children older than 2 years: Social Communication Questionnaire (SCQ) 4years + Social Responsiveness Scale (SRS) 4 18 years * all parent questionnaires Next Step? Formal diagnostic evaluation to include: Medical work up: Screening hearing and vision Unusual features dysmorphology, regression, staring spells, etc. Organic etiologies infectious, metabolic, endocrinologic, traumatic, toxic Genetic next page Behavioral assessment: One of the many assessment tools Assessment tools are never a substitute for informed clinical judgment. Genetic Work Up Why? Identify pathologic variant that can have immediate treatment or prognostic implications Identify context for complex behavioral symptoms Provide clinical roadmap Provide better understanding of heritability Provide answers for parents, leading to support 1

2 Slide 4 KK1 no cost to pediatricians and general practiciners Koth, Kathleen, 1/27/2017

3 Genetic Tests Genetic Tests Chromosomal Microarray All individuals with delays Fragile X Gene Testing All boys and girls with ID or a family history of ID PTEN Gene Testing If head circumference is greater than 2.5 SD above age mean MeCP2 Gene Testing For Rett s syndrome in girls with ID, developmental regression, seizure, and hand movements Specific Genetic Testing Tuberous sclerosis, Prader Willi, Angelman If no variants are found in the above and there is evidence of unresolved clinical findings: Could refer to genetics Look for rare imprinting or mitochondrial syndromes Whole exome sequencing (WES) Sequencing of all genes in the genome Does not identify variations outside gene regions KK2 Karyotype analysis Examination of chromosomes for abnormalities But clinical information gathered by the physician is key in knowing if an identified variant is pathological or benign. They are labeled variants of unknown significance if they have not previously been associated with developmental disabilities. Diagnostic Criteria DSM 5 Pervasive Developmental Disorders (PDD) are now Autism Spectrum Disorders (ASD). Rett s Syndrome and Childhood Disintegrative Disorder have been removed. For autism, all the previous diagnoses have been merged into one, behaviorally defined disorder. Three diagnostic domains are now two. For others, an etiologic subtype is described with the qualifiers. A B C marked impairment in the use of multiple nonverbal behaviors such as eye to eye gaze, facial expression, body postures, and gestures to regulate social interaction failure to develop peer relationships appropriate to developmental level a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest lack of social or emotional reciprocity delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime) in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others stereotyped and repetitive use of language or idiosyncratic language Lack of varied, spontaneous make believe play or social imitative play appropriate to developmental level encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus apparently inflexible adherence to specific, nonfunctional routines or rituals stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole body movements persistent preoccupation with parts of objects Deficits in social emotional reciprocity Deficits in nonverbal communicative behaviors used for social interaction Deficits in developing, maintaining, and understanding relationships Stereotyped or repetitive motor movements, use of objects, or speech Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior Highly restricted, fixated interests that are abnormal in intensity or focus Hyper or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment. A B Autism Spectrum Disorder A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history: 1. Deficits in social emotional reciprocity 2. Deficits in nonverbal communicative behaviors used for social interaction 3. Deficits in developing, maintaining, and understanding relationships B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history: 1. Stereotyped or repetitive motor movements, use of objects, or speech 2. Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior 3. Highly restricted, fixated interests that are abnormal in intensity or focus 4. Hyper or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment. C. Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies later in life). D. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning. E. These disturbances are not better explained by intellectual disability or global developmental delay. Intellectual disability and autism spectrum disorder frequently co occur; to make comorbid diagnoses of autism spectrum disorder and intellectual disability, social communication should be below that expected for general developmental level. Intervention Assist the family in obtaining evidence based behavioral and educational intervention. Structured behavioral and educational interventions have been shown to improve patient outcomes. Sparse literature in this area with good randomized group comparisons Lack subject characterization Attention to generalization of treatment effects Fidelity of treatment implementation AACAP Practice Parameter: Autism,

4 Slide 8 KK2 Whole Genome seuqencing dose but is not yet comercially available Koth, Kathleen, 1/27/2017

5 KK3 Behavioral Therapy Theory: Operant Conditioning Behaviors are taught: One on one treatment Intensive parent training Reward based Close support of other therapists and supervisors Vary in: Location: school vs. home vs. center Time: few hours a week vs. every day Intensity Curriculum used Applied Behavioral Analysis (ABA) Steps: Analyze the behavior for meaning and purpose. Structure an intervention. Reward success. Repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat, repeat! Goals: Increased frequency of desired behaviors Sustained desired behaviors after a shift in treatment Generalization to other settings very difficult Applied Behavioral Analysis (ABA) Various methods or curriculum have been developed: Lovaas TEACH LEAP Educational A structured approach with explicit teaching Focuses on child s weaknesses and strengths Focuses on improved communication Focuses on improved socialization Incorporates physical needs with PT and OT Models with good evidence base: Early Start Denver Model Treatment and Education of Autism and Related Communication Handicap Children Program Medication Management Why? increase the ability of a person with autism to benefit from educational and other therapeutic modalities allow the person to remain in less restrictive environments by controlling challenging behavior Medication Management Targets of Medication: Co Morbid Conditions: ADHD Anxiety Depression Difficult Behaviors: Aggression Self injurious behavior Hyperactive/impulsive behaviors Rigidity, issues with routines, compulsions Repetitive or stereotypic behaviors Sleep disturbances Medications do not TREAT autism or CURE autism 3

6 Slide 14 KK3 Has been used in : HIV prevention, conservation of natural resources, education, health and exercise, language acquisition, parenting, sports, littering, substance abuse, and zoo animals. A group out of university of Washington in the 1960 s began to work with this theory to teach social behavior. Lovass was a member of this group and in 1965 wrote two papers on using this in autism. Synonyms for ABA include: Organizational behavior management, positive behavior support, clinical behavior analysis including contingency management, acceptance, and commitment therapy (ACT), and habit reversal training. Only later did the term ABA come to apply only to autism. Koth, Kathleen, 1/27/2017

7 Risperidone Aripiprazole FDA approved for 5 years and older for autism and associated irritability Benefits: irritability, hyperactivity, stereotypy, social withdrawal, inappropriate speech, rigidity Risks: weight gain, metabolic syndrome, sedation or fatigue, dizziness, drooling, increased appetite, gynecomastia, long term use osteoporosis Dosing: start super low and go slow; it is a potent med Second Generation Antipsychotic Monitoring Abrupt discontinuation is not recommended due to risk of withdrawal dyskinesia. FDA approved for ages 6 to 17 years for autism and associated irritability Benefits: irritability, hyperactive, stereotypy Risks: weight gain, metabolic changes, somnolence, drooling, tremor, vomiting Dosing: Start low and go slow. Very slow long half life so will see effects of your change weeks later Second Generation Antipsychotic Monitoring Abrupt discontinuation is not recommended due to risk of withdrawal dyskinesia. Second Generation Antipsychotic Monitoring Baseline: BP, BMI, waist circumference, AIMS, fasting lipids, fasting glucose, counseling about diet, life style, and side effects EKG if high risk 4 weeks BMI 6 weeks BMI 12 weeks BMI, fasting lipids, fasting glucose Every 6 months: BP, BMI, waist circumference, fasting lipids, fasting glucose, dietary counseling Annually: AIMS Nothing Else is FDA approved for Autism Because we are not treating to cure autism; we are treating the symptoms and the co morbidities. Therefore, use the guidelines for the co morbidities with caution. These kids are more sensitive to medications. They get more side effects. Small adjustments can make huge differences. All the rest of the talk is off label. Alpha 2 Agonists Guanfacine and clonidine Little research: Benefits: hyperactivity, irritability, inappropriate speech, stereotypy Risks: increased irritability, hyperactivity, drowsiness, hypotension Can be beneficial: Avoid the side effects of antipsychotics Dosing: Low and slow Increased irritability and worsening agitation can come quickly Stimulants Some research Target: hyperactivity, inattention Side effects: increased irritability, agitation, appetite suppression, insomnia, increased emotionality Can be beneficial if works for hyperactivity: But can make behaviors much worse Easier trial because quick to leave the system 4

8 SSRIs For Parents Some research Targets: repetitive behaviors, stereotypy, irritability Side effects: hyperactivity, impulsivity, inattention, insomnia, twitching, tremor, lethargy, tachycardia, diaphoresis, nausea Can be beneficial in some kids: Rigidity and need for routine obsessions that prevent functioning Worries, nervousness that prevent basic functioning Very low dose watch carefully for agitation even 6 8 weeks later AACAP has a new medication guide for parents: s/autism/autism_spectrum_disorder_parents_medication_guide.p df For Parents Autism Speaks Medication Guide: For Parents ces programs/autism treatmentnetwork/tools you can use/sleep tool kit n/medication_safe_and_careful_use.pdf References AAP Statement on U.S. Preventive Services Task Force Final Recommendations on Autism Screening (February 2016) Diagnostic and Statistical Manual of Mental Disorders (5 th ed.). Washington, DC: American Psychiatric Association. Fung, L. K., R. Mahajan, A. Nozzolillo, P. Bernal, A. Krasner, B. Jo, D. Coury, A. Whitaker, J. Veenstra Vanderweele and A. Y. Hardan (2016). "Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta analysis." Pediatrics 137 Suppl 2: S Ji, NY. Findling, R.L. An update on pharmacotherapy for autism spectrum disorder in children and adolescents. Current Opinion in Psychiatry, 2015, 28: Johnson, C.P., Meyers, S.E., COCWD, Identification and Evaluation of Children With Autism Spectrum Disorders, Pediatrics, November 2007, Reaffirmed 2010;2014 (clinical report) Practice Parameter for the Assessment and Treatment of Children and Adolescents With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry. 2014;53(2): Machado JD, Caye A, Frick PJ, Rohde LA. DSM 5. Major changes for child and adolescent disorders. In Rey JM (ed), IACAPAP e Textbook of Child and Adolescent Mental Health. Geneva: International Association for Child and Adolescent Psychiatry and Allied Professions McGuire, K., L. K. Fung, L. Hagopian, R. A. Vasa, R. Mahajan, P. Bernal, A. E. Silberman, A. Wolfe, D. L. Coury, A. Y. Hardan, J. Veenstra VanderWeele and A. H. Whitaker (2016). "Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care." Pediatrics 137 Suppl 2: S Muhul, R, et all. Clinical Diagnostic Genetic Testing For Individuals with Autism Spectrum Disorder, Intellectual Disability or Global Developmental Delay, Submitted for publication. 5

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