Marcie Hall, M.D.Department of Child and Adolescent Psychiatry

University Hospitals Case Medical Center

Autism SummitOctober 10, 2008

Medication Use in The ASD Population

Topics Clinical features of Autism Spectrum

Disorders Areas of problematic behaviors Treatment options Medications Future Directions

Autism Spectrum Disorders Five conditions: Autism Asperger’s Disorder Pervasive Developmental Disorder

Not Otherwise Specified Rett’s Disorder Childhood Disintegrative Disorder

PDD’s - Core Features

Three main areas of dysfunction: Socialization Communication Restricted, repetitive stereotyped

patterns of behavior

Epidemiology

Autism Asperger’s PDD NOS

Treatments

There is no pharmacologic cure for the Autism Spectrum Disorders

Treatment requires a multimodal approach

Behavioral, educational, rehabilitative, support for family

Symptomatic Treatments

Inattention, Hyperactivity, Impulsivity Irritability Aggression Self-injurious Behaviors Stereotypy and Repetitive Behaviors Sleep Disturbance Core Social and Communication

Impairment

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

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

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

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.

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

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

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

Irritability, Aggression and Self-Injurious Behaviors

Atypical Antipsychotics Risperidone (Risperdal) Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel) Ziprasidone (Geodon Aripiprazole (Abilify)

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.

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

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

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)

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

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®)

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.

Stereotypic and Repetitive Behaviors

Side effects of SSRI’s: Mild sedation, lethargy Nausea Change in appetite Insomnia Behavioral activation Akathisia

FDA Mandated Warning

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

Stereotypic and Repetitive Behaviors

Clomipramine: a tricyclic

antidepressant, very helpful, but

concerns about side effects

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

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

Deficits in Social Behavior

Medications needing more study:

D-Cycloserine

Tetrahydrobiopterin

Oxytocin

TADS, 2007

Deficits in Social Behavior

Medications NOT effective: Fenfluramine Naltrexone

Complementary and Alternative Medicine

Mind-body Supplements Omega 3 fatty acids Gluten free, casein free diet Secretin GI medications Auditory integration, music therapy

Complementary and Alternative Medicine

Unconventional: Hyperbaric oxygen Chelation Immune therapies Antibiotics, antifungals

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.