1. Marcie Hall, M.D. Department of Child and Adolescent Psychiatry University Hospitals Case Medical Center Autism Summit October 10, 2008 Medication Use in The ASD Population

2. Topics  Clinical features of Autism Spectrum Disorders  Areas of problematic behaviors  Treatment options  Medications  Future Directions

3. Autism Spectrum Disorders  Five conditions:  Autism  Asperger’s Disorder  Pervasive Developmental Disorder Not Otherwise Specified  Rett’s Disorder  Childhood Disintegrative Disorder

4. PDD’s - Core Features  Three main areas of dysfunction:  Socialization  Communication  Restricted, repetitive stereotyped patterns of behavior

5. Epidemiology  Autism  Asperger’s  PDD NOS

6. Treatments  There is no pharmacologic cure for the Autism Spectrum Disorders  Treatment requires a multimodal approach  Behavioral, educational, rehabilitative, support for family

7. Symptomatic Treatments  Inattention, Hyperactivity, Impulsivity  Irritability  Aggression  Self-injurious Behaviors  Stereotypy and Repetitive Behaviors  Sleep Disturbance  Core Social and Communication Impairment

8. Inattention, Hyperactivity and Impulsivity  Attention-Deficit Hyperactivity Disorder  Children with PDD’s have very high rates of ADHD symptoms  Symptoms can impede treatment and decrease quality of life for our patients and their families

9. Treating ADHD-Like Symptoms  Psychostimulants  Methylphenidate: Used extensively in typically-developing children and adolescents with ADHD. By comparison, ASD patients have somewhat less symptom amelioration and more side effects (RUPP study)  Amphetamines: Few studies and results were highly variable

10. Non-Stimulant Treatments  Atomoxetine (Strettera) Again, few studies and highly variable responses. Not as much improvement and some increase in side effects compared to typically- developing children

11. Non-Stimulant Treatments  Antidepressants:  Tricyclics like imipramine, desipramine, amitriptyline, clomipramine, notrriptyline have been used historically, but recent concerns about cardiac toxicity have curbed use.  SSRI’s: mainly used to treat depression  Venlafaxine: two published studies have suggested efficacy, but several reports raise concern that restlessness is a frequent side effect, and can increase hyperactivity.

12. Non-Stimulant Treatments  Alpha-2 Adrenergic Agonists  Clonidine (Catapres): studies have had small sample sizes, but seem to show a decrease in sensory responses and oppositionality. Side effects include sedation, fatigue, decreased activity  Guanficine (Tenex): similar reduction in overactivity, but caused sedation, constipation and occasionally, sleep disruption

13. Non-Stimulant Treatments  Cholinesterase Inhibitors: Alzheimer’s Disease Treatments  Post-mortem studies have shown an abnormality in the cholinergic system in the brains of people with autism  Donepazil  Galantamine  Memantine

14. Irritability, Aggression and Self-Injurious Behaviors  Typical Antipsychotics  Many, but particularly Haloperidol, has been used to successfully reduce maladaptive behaviors (aggression, temper tantrums, withdrawal, stereotypies).  Main concern is side effects: sedation, acute dystonias, dyskinesias

15. Irritability, Aggression and Self-Injurious Behaviors  Atypical Antipsychotics  Risperidone (Risperdal)  Clozapine (Clozaril)  Olanzapine (Zyprexa)  Quetiapine (Seroquel)  Ziprasidone (Geodon  Aripiprazole (Abilify)

16. Irritability, Aggression and Self-Injurious Behaviors  Risperidone has been approved by the FDA for the treatment of irritability and aggression in children and adolescents with autism aged 5-16 years  Largely due to the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network, which demonstrated a decrease in irritability, tantrums, aggressive, self-injurious and stereotypic behaviors.

17. Irritability, Aggression and Self-Injurious Behaviors  Side effects of many of the Atypical Antipsychotics (Olanzapine, Risperidone, Quetiapine) include:  Weight gain  Mild to moderate increase in appetite  Fatigue, drowsiness, sedation  Constipation  Metabolic problems

18. Irritability, Aggression and Self-Injurious Behaviors  Newer atypical antipsychotics, such as Ziprasidone and Aripiprazole are currently being studied for efficacy in the ASD population  They appear to be well tolerated, with less weight gain than the older atypicals, but may not be as effective in reducing maladaptive behaviors

19. Irritability, Aggression and Self-Injurious Behaviors  Antiepileptics: Seizure disorders are common in people with ASD’s.  Further studies are needed to determine the efficacy and safety of these medications in the ASD population  Divalproex Sodium (Depakote)  Lamotrigine (Lamictal)  Topiramate (Topamax)

20. Stereotypic and Repetitive Behaviors  Restricted, repetitive behaviors can often interfere with treatment in the ASD population  These impairments are similar to the obsessions and compulsions found in OCD  Improvement in this domain can significantly improve overall outcomes for individuals with ASD’s

21. Stereotypic and Repetitive Behaviors A mainstay of treatment has become the SSRI’s or Selective Serotonin Reuptake Inhibitors:  Fluoxetine (Prozac ® )  Sertraline (Zoloft ® )  Paroxetine (Paxil ® )  Fluvoxamine (Luvox ® )  Citalopram (Celexa ® )  Escitalopram (Lexapro ® )

22. Stereotypic and Repetitive Behaviors  Fluoxetine has been shown to improve overall functioning in patients with ASD’s, with positive effects on language, cognition, social relatedness and affect.  Also, a decrease in irritability, lethargy, stereotypy and inappropriate speech has been noted.

23. Stereotypic and Repetitive Behaviors  Side effects of SSRI’s:  Mild sedation, lethargy  Nausea  Change in appetite  Insomnia  Behavioral activation  Akathisia

24. FDA Mandated Warning

25. SSRI & Suicidal Ideation  No reports of completed suicides  Studies did not include ASD population  SSRI use associated with decreased suicide rate  Studies found no association between SSRI use and completed suicide

26. Stereotypic and Repetitive Behaviors  Clomipramine: a tricyclic antidepressant, very helpful, but concerns about side effects

27. Sleep Disturbance  Commonly, people with ASD’s suffer with disturbed sleep patterns  Insomnia: most common problem in ASD’s, can be caused by neurobiology, behavior, coexisting medical disorder (GI, epilepsy) or psychiatric disorder (anxiety), medications, obstructive sleep apnea, restless leg syndrome

28. Sleep Disturbance  After thorough assessment to rule out other causes, can use:  Melatonin  Medications used for another disorder (epilepsy) that are also sedating  Risperidone  Clonidine

29. Deficits in Social Behavior  Medications needing more study:  D-Cycloserine  Tetrahydrobiopterin  Oxytocin TADS, 2007

30. Deficits in Social Behavior  Medications NOT effective:  Fenfluramine  Naltrexone

31. Complementary and Alternative Medicine  Mind-body  Supplements  Omega 3 fatty acids  Gluten free, casein free diet  Secretin  GI medications  Auditory integration, music therapy

32. Complementary and Alternative Medicine  Unconventional:  Hyperbaric oxygen  Chelation  Immune therapies  Antibiotics, antifungals

33. Conclusion  Many symptoms can be helped by currently available therapies to improve the lives of people living with ASD’s.  More research is ongoing and ASD’s have captured the imagination of investigators around the world.