CE on SUNDAY Melville, NY September 20, 2009

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1 CE on SUNDAY Melville, NY September 20, 2009 Date: Sunday, September 20, 2009 Time: 9:15 AM 10:30 AM Location: Melville Marriott Long Island Title: Speaker(s): Inside the Unknown World of Autism ACPE # L01-P CEU ACPE # L01-T CEU Scott Stolte, Pharm.D., Shenandoah University Learning Objectives: Upon completion of this activity, participants will be able to: 1. Describe the etiology, pathogenesis and common clinical findings of autism. 2. Compare and contrast the conditions that comprise the autism spectrum disorders. 3. Evaluate common myths associated with autism and patients with autism. 4. Describe the non-pharmacological treatment of autism. 5. List the medication options for patients with autism. 6. Given adequate patient information, design a complete (nonpharmacological and pharmacological) treatment plan for a patient with autism. Disclosures: Scott Stolte, Pharm.D., Shenandoah University declares no conflicts of interest or financial interests in any product or service mentioned in this program, including grants, employment, gifts, stock holdings, or honoraria. Speaker(s) Biography: Dr. Scott Stolte joined the faculty of the Bernard J. Dunn School of Pharmacy at Shenandoah University in Scott served as a faculty member and as Chair of the Department of Pharmacy Practice prior to assuming his position as Associate Dean for Academic Affairs. Dr. Stolte earned his Doctor of Pharmacy degree from Purdue University in West Lafayette, IN in After graduation, Dr. Stolte was the initial community pharmacy resident at Family PharmaCare, Inc. and Purdue University. Scott completed the American Association of Colleges of Pharmacy (AACP) Academic Leadership Fellowship program in While maintaining his interest in progressive community pharmacy practice and primary care disease state management, he has expanded his areas of teaching, service, and scholarship to include distance education, educational assessment, experiential education, and the application of leadership skills and traits to pharmacy and academic medicine.

2 Inside the Unknown World of Autism Scott Stolte, Pharm.D. Associate Dean, Academic Affairs Bernard J. Dunn School of Pharmacy Shenandoah University April 24, 2009 This program has been brought to you by PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

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4 What is it? Neurobiologic/Neurodevelopmental disorder Lasts a person s s lifetime No direct decrease of life expectancy All racial, ethnic, social groups Four times more likely in boys Symptoms range from very mild to very severe

5 Proposed Etiology Genetic Multiple genes implicated ID twins 60-90% concordance Sibling with autism 4-10% risk Next step Environmental stressor or toxicant Documented prenatal or early postnatal viral infections, valproic acid, thalidomide

6 Other Consistent Findings Infant Head Size Start with same size or slightly smaller brain Brain size increases more from months of age Mirror Neuron Dysfunction fmri observed abnormalities of brain activity when observing or imitating emotions Dysregulation of serotonin Seizure disorder (30%) Mental retardation (60-70% with full syndrome autism)

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9 Three Major Deficits: Impairment in Communication Skills Impairment in Social Abilities Social Reciprocity Breadth of Interest - Rigid Routines, Restricted Interests, and/or Repetitive Behaviors

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11 Associated Behavioral Problems Hyperactivity Impulsivity Anxiety Irritability Aggression These are targets of drug treatment.

12 Autism Spectrum Disorders Autism Asperger Syndrome Rett Syndrome Childhood Disintegrative Disorder PDD-NOS

13 Diagnosis Reliable at age 2, most commonly made at 3 As young as 6 months Failure to reach appropriate developmental milestones Early intervention is critical If at least two years during the preschool years significant improvement Interventions focused on communication, social skills, cognitive skills

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16 Facts about Autism 1 in in 94 boys is on the autism spectrum 67 children are diagnosed d per day A new case is diagnosed almost every 20 minutes More children will be diagnosed with autism this year than with AIDS, diabetes & cancer combined

17 More Facts About Autism Autism is the fastest-growing g serious developmental disability in the U.S. Autism costs the nation over $90 billion per year, a figure expected to double in the next decade Autism receives less than 5% of the research funding of many less prevalent childhood d diseases Boys are four times more likely than girls to have autism There is no medical detection or cure for autism

18 Incidence vs. Funding Leukemia: Affects 1 in 25,000 / Funding: $310 million Muscular Dystrophy: Affects 1 in 20,000 / Funding: $175 million Pediatric AIDS: Affects 1 in 8,000 / Funding: $394 million Type 1 Diabetes: Affects 1 in 500 / Funding: $130 million Autism: Affects 1 in 150 / Funding: $15 million

19 NIH Funding Total 2005 NIH budget: $29 billion Of this, only $100 million goes towards autism research. This represents 0.3% of total NIH funding.

20 Red Flags of Autism No big smiles or other warm, joyful expressions by six months or thereafter No back-and and-forth sharing of sounds, smiles, or other facial expressions by nine months or thereafter No babbling by 12 months No back-and and-forth gestures, such as pointing, showing, reaching, or waving by 12 months No words by 16 months No two-word word meaningful phrases (without imitating or repeating) by 24 months Any loss of speech or babbling or social skills at any age

21 The diagnosis is devastating. Stages of grief will be experienced by family and friends Shock initial paralysis at hearing the news Denial Anger Bargaining seeking a way out Depression realization of the inevitable it Testing Seeking realistic solutions Acceptance finding the way forward

22 Vaccines and Autism Very emotional issue don t beanexpert expert unless you are one This talk is not designed to make you an expert. As of right now no definitive iti link Lancet study MMR vaccine implicated Study authors now acknowledge shortcomings Large European RCCTs no link

23 Treatments for Autism Occupational Therapy Speech Therapy Verbal Behavior Intervention ti TEACCH (Training and Education of Autistic and Related Communication Handicapped Children) Relationship Development Intervention (RDI) Floortime

24 Applied Behavioral Analysis (ABA) Positive reinforcement for a behavior by arranging for it to be followed by something of value to the person Useful for communication, play, social interaction, academic work, self care, community living ing skills, reduction in problem behavior Skills broken down into small steps Customized for every individual

25 Sensory Integration Therapy Sensory Integration - the process through which the brain organizes and interprets external stimuli such as movement, touch, smell, sight and sound. Autistic children often exhibit symptoms of Sensory Integration Dysfunction (SID) making it difficult for them to process information brought in through the senses. Hypersensitive Hyposensitive No pain phenomenon

26 Sensory Integration Therapy The goal of Sensory Integration Therapy is to facilitate the development of the nervous system's ability to process sensory input in a more typical way. Sensory stimulation is given to the child, often in conjunction with purposeful muscle activities, to improve how the brain processes and organizes sensory information. The therapy often requires activities that consist of full body movements utilizing different types of equipment.

27 Examples of SIT Swinging i in a hammock (movement through h space) Dancing to music (sound) Playing in boxes filled with beans (touch) Crawling through tunnels (touch and movement through space) Hitting swinging balls (eye-hand coordination) Balancing on a beam (balance)

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31 Autism and School Individuals with Disabilities Education Improvement Act 2004 state must provide all eligible children with a free and appropriate public education that meets their unique individual needs. Autism specifically listed as a disability Parent is entitled to be treated as an equal partner in deciding on an educational plan that contains the elements that your child needs.

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33 Medication Options for Autism No medications alter CNS abnormalities For now, medication aimed at behavioral symptoms Medications include: Stimulants α 2 -Agonists Antidepressants Anticonvulsants Antipsychotics Others/Alternative treatments

34 Stimulants Methylphenidate Commonly prescribed for autism and PDDs Small number of controlled studies Improvement in hyperactivity, impulsivity, and attention Increased stereotypy and irritability Other adverse effects Dysphoria, social withdrawal, crying, insomnia, anorexia, aggression, tics, agitation

35 α 2 -Agonists Main role is in treating hyperactivity Clonidine Oral and transdermal Improvement in hyperactivity and agitation Sedation common, some hypotension Guanfacine Less data 24% response rate

36 Antidepressants Tricyclic antidepressants Limited data Not often used because not well tolerated Clomipramine Serotonin reuptake blocker Varying success and adverse effects Reduces repetitive behaviors and thoughts Reduces aggression and anger Improved eye contact and verbal responsiveness May increase seizure risk Less effective in younger children than adults and adolescents

37 Various agents used SSRIs Fluoxetine most studied d in children and adults Benefits reduced rituals, stereotypies, repetitive behaviors, and overadherence to routines Adverse effects agitation, hyperactivity, hypomania, disinhibition Similar benefits and adverse effects with fluvoxamine Others: sertraline, paroxetine, citalopram, escitalopram

38 Venlafaxine 10 patient case series Mean dose 24 mg/day 60% response rate Improvement in repetitive behaviors, restricted interest, social deficits, communication and language, inattention, and hyperactivity Adverse effects agitation, hyperactivity y

39 Anticonvulsants Divalproex sodium Used to treat mood instability In PDD, improved affective instability, impulsivity, and aggression 71% response rate All pts. with seizures and abnormal EEG responded Lamotrigine and levetiracetam also used, questionable efficacy

40 Antipsychotics Typical antipsychotics have been used Haloperidol has demonstrated efficacy Others used Concern over EPS and tardive dyskinesia Atypical agents used more commonly

41 Clozapine Primarily used for treatment resistant patients Improves aggression and hyperactivity Limited use: Required hematologic monitoring Lowered seizure threshold

42 Risperidone Most researched medication, FDA indication Efficacy compared to placebo confirmed by 3 double-blind, blind, placebo-controlled controlled trials 60-70% response rate Average doses used mg/day Primary efficacy is to reduce aggression and irritability Also effective for repetitive behavior, depression, anxiety, and nervousness Adverse effects transient sedation, weight gain, increased appetite

43 Other Atypical Antipsychotics Olanzapine No strong, controlled trials Low EPS risk Quetiapine Two open label trials Minimal efficacy Ziprasidone Retrospective case series, some benefit Aripiprazole No placebo-controlled controlled trials, possible benefit

44 Other agents Buspirone Several small, prospective trials Benefits - anxiety, irritability, tantrums, hyperactivity Dosed mg/day Propranolol Case series Benefits aggression, anxiety, hyperarousal

45 D-Cycloserine Other agents Placebo-controlled controlled case series Improved social responsiveness Cholinesterase inhibitors (donepezil, galantamine, rivastigmine) No placebo-controlled controlled trials Benefit dysfunctional behaviors, hyperactivity, i expressive speech Naltrexone Extensively studied, minimal benefit, little use

46 Amantadine/Memantine Increasing interest on interactions between glutamatergic and dopaminergic systems and expressions of impulsivity, hyperactivity and stereotypy Amantadine Indirect dopamine agonist, NMDA receptor antagonist mixed results in trials Memantine NMDA receptor antagonism Open label studies report benefit, larger studies underway

47 Other/Alternative treatments GF-CF diet studies not convincing Omega-3 fatty acids for hyperactivity mixed results Secretin multiple trials have not demonstrated t d efficacy Vitamins/Nutritional supplements Vitamin B6 and dimethylglycine (DMG) not superior to placebo Chelation therapy two trials underway

48 Autism Thoughts and Quotes AUTISM IS A SEPARATE WORLD: LOVE CAN BUILD A BRIDGE AUTISM: WORDS A PART, WORLDS APART A MIND IS A TERRIBLE THING DISPLACED AUTISTIC FORECAST FOR TODAY: SCATTERED BRAINSTORMS RAIN MAN FOR PRESIDENT: HEY, THE PRESS CONFERENCES WILL BE INTERESTING

49 Thanks for your time and attention!

50 References Quintana H, Birmaher B, Stedge D, et al. Use of methylphenidate in the treatment of children with autistic disorder. J Autism Dev Disord 1995;25: Jaselskis CA, Cook EH Jr., Fletcher KE, et al. Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 1992;12: Gordon CT, State RC, Nelson JE. A double-blind blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry 1993;50: DeLong GR, Ritch CR, Burch S. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. Dev Med Child Neurol 2002;44: Hollander E, Kaplan A, Cartwright C, et al. Venlafaxine in children, adolescents, and young adults with autism spectrum disorders: an open, retrospective clinical report. J Child Neurol 2000;15: Hollander E, Dolgoff-Kaspar R, Cartwright C, et al. An open trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry 2001; 62: Mikkelsen EJ. Efficacy of neuroleptic medication in pervasive developmental disorders of childhood. Schizophr Bull 1982;8: Zuddas A, Ledda MG, Fratta A, et al. Clinical effects of clozapine on autistic disorder [letter]. Am J Psychiatry 1996;153:738. Mukkades NM, Abali O, Gurkan K. Short-term term efficacy and safety of risperidone in young children with autistic disorder. World J Biol Psychiatry 2004;4: McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl JMed 2002;347: Shea S, Turgay A, Carroll A, et al. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics 2004;114:e634-e641. e641. Stavrakaki C, Antochi R, Emery PC. Olanzapine in the treatment of pervasive developmental disorders: a case series analysis. J Psychiatry Neurosci 2004;29: Realmuto GM, August GJ, Garfinkel BD. Clinical effect of buspirone in autistic children. J Clin Psychopharmacol 1989;9: Ratey JJ, Mikkelsen E, Sorgi P, et al. Autism: the treatment of aggressive behaviors. J Clin Psychopharmacol 1987;7: Kolmen BK, Feldman HM, Handen BN, et al. Naltrexone in young autistic children: replication study and learning measures. J Am Acad Child Adolesc Psychiatry 1997;36: Aman MG, Van Bourgondien ME, Wolford PL, et al. Psychotropic and anticonvulsant drugs in subjects with autism: prevalance and patterns of use. J Am Acad Child Adolesc Psychiatry 1995;34: Erickson CA, Posey DJ, Stigler KA, et al. Pharmacologic treatment of autism and related disorders. Pediatr Ann 2007;36; Leskovec TJ, Rowles BM, Findling RL. Pharmacologic treatment options for autism spectrum disorders in children and adolescents. Harv Rev Psychiatry 2008;16: