Evaluating the Effectiveness of Aripiprazole and D-Cycloserine to Treat Symptoms Associated With Autism

Autism is a developmental disorder that affects every child differently. A wide range of
symptoms accompany autism, including self-injurious behavior, aggression, and severe
tantrums. Despite an improved ability to reduce these symptoms, existing drug treatments
continue to be associated with adverse side effects. Also, there is no existing drug
treatment that reliably improves social behavior, a core deficit in autism. Studies on drug
treatment combinations that are designed to reduce self-injurious behavior, aggression, and
severe tantrums and improve social behavior in children with autism have yet to be conducted.
This study will address the above-mentioned limitations by evaluating aripiprazole in
reducing self-injurious behavior, aggression, and severe tantrums and by evaluating the
addition of D-Cycloserine in improving social behavior among children with autism.

This study will include three phases and an add-on component for some children. Participants
will be randomly assigned to receive either aripiprazole or a placebo treatment for 8 weeks.
Assessments measuring irritability, behavior, and social skills will be conducted at the end
of this first phase. Those patients who respond well to aripiprazole will continue to receive
aripiprazole treatment for another 16 weeks. This second phase will determine whether
aripiprazole is associated with long-term maintenance of symptomatic improvement in patients
who respond well to short-term treatment. Assessments will again be conducted at the end of
this 16-week period. Those patients whose symptoms have stabilized and continue to improve
while on aripiprazole will be asked to participate in the final phase of this study. During
the this pilot phase, D-Cycloserine will be added to ongoing treatment with aripiprazole.
Patients will take both aripiprazole and D-Cycloserine for an additional 8 weeks to determine
if this combination of drug treatments results in improved social behavior once patients'
aggression and self-injurious behavior have been stabilized with aripiprazole. At the end of
this 8-week period, participants will be assessed for any changes in behavior, irritability,
or social skills. Results from this study may aid in developing safer and more effective drug
treatments for children and adolescents with autism.

Inclusion Criteria:

- Weight of at least 15 kg (33.75 lbs)

- Meets DSM-IV criteria for autistic disorder

- Outpatient

- Medication-free for at least 2 weeks prior to baseline for all psychotropic
medications. More information about this criterion, including exceptions, can be found
in the protocol.

- Clinical Global Impression Scale Severity score (CGI-S) of at least 4

- Irritability subscale of the Aberrant Behavior Checklist (ABC) score of at least 18

- An IQ of at least 35 or a mental age of at least 18 months

- In good physical health

Exclusion Criteria:

- Meets DSM-IV criteria for Asperger's disorder, Rett's disorder, childhood
disintegrative disorder, any other pervasive developmental disorder (PDD),
schizophrenia, psychotic disorder, or bipolar disorder

- Current or past history of alcohol or other substance abuse within 6 months of study
entry

- Comorbid neurodevelopmental disorder with possible association to autism (e.g.,
fragile-X syndrome, tuberous sclerosis)

- A significant medical condition such as heart, liver, kidney, or lung disease, or a
seizure disorder

- Pregnant

- Prior adequate use of aripiprazole. More information about this criterion can be found
in the protocol.

- Evidence of hypersensitivity to aripiprazole

- History of neuroleptic malignant syndrome