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Master Slide

Master Slide. Current Trends in the Pharmacological Treatment of Autism . Alexander Kolevzon, MD Peter Della Bella, MD David Grodberg, MD Charles Cartwright, MD. Symptom Domains and Associated Features of ASD. Social Phobia. Social Impairment. EEG Abnormalities. ADHD Symptoms.

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  1. Master Slide Current Trends in the Pharmacological Treatment of Autism Alexander Kolevzon, MD Peter Della Bella, MD David Grodberg, MD Charles Cartwright, MD

  2. Symptom Domains and Associated Features of ASD Social Phobia Social Impairment EEG Abnormalities ADHD Symptoms Asperger’s syndrome AUTISM Impulsivity/ Aggression Speech/ Communication Deficits Repetitive Behaviors Obsessive Compulsive Disorder Expressive/Receptive Language Disorders

  3. Treating Agitation and Aggressionin People with ASDs Peter Della Bella, MDDirector of Clinical ProgramsPremier HealthCare

  4. ADHD Symptoms and Autism Spectrum Disorders: Co-Occurrence, Phenomenology, and Treatment David Grodberg, M.D. Seaver Autism Center

  5. The Treatment of Anxiety and Repetitive Behaviors in Autism Spectrum Disorders Alex Kolevzon, M.D. Clinical Director, Seaver Autism Center

  6. Future DirectionsTargetingNovel Neurotransmitter and Hormonal SystemsIn Autism Charles Cartwright, MD Director, YAI Autism Center

  7. Master Slide Agitation and Aggression Peter Della Bella, MD

  8. What is Agitation? An inability to cope causing distress… and losing control Precursors: Irritability, anxiety, fatigue… The worry: add a trigger and…

  9. What is Aggression? (Latin) Attack Premeditated vs. loss of impulse control

  10. Understanding the Roots of Agitation and Aggression

  11. Roots of Irritability & Agitation- the Fight or Flight Response Sources: Babble.com; Brain-trainer.com; quantumlearningblog

  12. Roots of Agitation and Aggression ATTACK loss of control agitated coping irritated c a l m

  13. Roots of Agitation and Aggression • Survival instinct (“Boxed into a corner”) • Pain/physical discomfort (sensory integration) • Psychic discomfort (stress, change, frustration)

  14. Roots of Agitation and Aggression ATTACK agitated irritated c a l m

  15. Roots of Agitation and Aggression stress, discomfort, pain ATTACK agitated c a l m / irritated

  16. Roots of Agitation and Aggression stress, discomfort, pain ATTACK agitated c a l m / irritated cultural, behavioral, “medical” factors

  17. What do you do? • Survival instinct…….. take care of the threat • Treat sources of physical discomfort, side effects… proper medical evaluation sensory integration principles • Treat sources of psychic discomfort….. soften the blow of change address stress (sleep, food, downtime, fun)

  18. Roots of Agitation and Aggression ATTACK agitated Irritated c a l m

  19. When do you use meds? • When there are underlying biological factors. Let the symptoms guide you! • Anxiety Disorder • Depression • ADHD • Psychosis • Seizure • Otherwise, MEDICATION IS A LAST RESORT

  20. FDA approved for autism… risperidone aripiprazole

  21. So what do we use?

  22. What are the pros and cons of using medications?

  23. Master Slide Attention Deficit and Hyperactivity David Grodberg, MD

  24. ADHD SYMPTOMS IN ASD • DSM-IV TR prohibits diagnosis of ADHD and ASD in the same individual • Clinic based surveys indicate that Sx c/w ADHD present in 41-78% of children with ASD

  25. ADHD SYMPTOMS IN ASD • Asperger’s Disorder, PDD-NOS who meet full criteria for ADHD • Autistic Disorder with ADHD-like symptoms, which are part of core features of autism • Autistic Disorder with increased motor activity, impulsivity, inattention

  26. ADHD SYMPTOMS IN ASD • Inattention to social stimuli but good sustained focus on interests or objects. NOT ADHD. • Hyperactivity as a manifestation of motor stereotypy, social anxiety, agitation, or medication side effects. NOT ADHD

  27. TREATMENT OF ADHD SYMPTOMS IN ASD • Strongest evidence: methylphenidate • 2 placebo-controlled trials • retrospective and prospective effectiveness study

  28. Methylphenidate Increases NE and DA by blocking reuptake

  29. Methylphenidate ASD+ADHD tolerated stimulants generally well ASD+ADHD had dysphoria and obsessionality - initiate methylphenidate in ASD at lower dose and increase dose slowly with frequent monitoring for side effects

  30. TREATMENT OF ADHD SYMPTOMS IN ASD • Moderate Level Evidence: guanfacine • chart review study • small open-label trial • Moderate Level Evidence: atomoxetine • small open label study • small placebo controlled study

  31. Guanfacine Alpha 2A agonist. Enhances prefrontal cortical function

  32. Atomoxetine Increases NE and DA in prefrontal cortex.

  33. TREATMENT OF ADHD SYMPTOMS IN ASD • Weak Support: clonidine, donepezil • very small studies

  34. Clonidine Nonselective alpha2 agonist. More sedating/hypotensive.

  35. Donepezil Acetyl Cholinesterase inhibitor

  36. SUMMARY • Children with ADHD symptoms and ASD are difficult to treat • stimulants (methylphenidate), atomoxetine, alpha-agonists are effective • SSRIs and atypical neuroleptics are used to address other types of symptoms

  37. CLINICAL PEARLS • If a child with ADHD is referred with poor response to meds and/or significant side effects (anxiety, stereotypy, aggression) - look for evidence of previously unrecognized ASD • If a stimulant is helpful but side effects of anxiety emerge, can switch to atomoxetine or add SSRI. • Monitor closely for behavioral disinhibition • hyperactivity, impulsivity, new odd/disorganized behavior, SI.

  38. Master Slide Anxiety and Repetitive Behaviors Alexander Kolevzon, MD

  39. Repetitive Behaviors A preoccupation with stereotyped and restricted patterns of interest Inflexibility in adhering to routines and rituals Stereotyped and repetitive motor mannerisms Persistent preoccupation with parts of objects Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)

  40. Higher Order (compulsive) Insistence on sameness Ritualistic behavior Circumscribed interests & preoccupation Repetitive Behaviors Lower Order (motor/sensory) Repetitive self-injury Motor stereotypies Sniffing/mouthing objects Touching Tapping Rubbing

  41. Higher Order (compulsive) Obsessions Repetitive Behaviors Lower Order (motor/sensory) Hoarding Anagnostou et al, 2005

  42. Serotonin System • Critical to neurodevelopment • Directs neuronal growth, proliferation, differentiation • Widely expressed in emotional centers of brain

  43. Emotional Center of Brain

  44. Serotonin Pathways

  45. Serotonin System in Autism

  46. Serotonin Reuptake Inhibitors

  47. Serotonergic Medications

  48. Serotonergic Medications

  49. Study of Fluoxetine in Autism (SOFIA) N=158

  50. Atypical Antipsychotics - Risperidone McDougle et al, 2005

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