Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism

This study compares divalproex sodium and placebo in the treatment of autistic disorder.
Twenty six child or adolescent outpatients, with age ranges from 5-17, will be randomized
into a 12-week double-blind, placebo-controlled parallel treatment study. During the 12
weeks, patients will be monitored by the treating psychiatrist and assessed by an independent
evaluator (IE). The IE will perform study assessments while remaining blind to medication
regimens (including possible tapering) as well as any side effects. Study assessments will be
administered at designated time points

Meets DSM-IV, ADI, and ADOS criteria for autistic disorder

Age 5-17.

Outpatients

Parent/legal guardian signing informed consent, and assent documented for patient with
demonstrated capacity to provide it.

Sexually active females of childbearing potential must use an acceptable method of birth
control (oral contraceptive medications [the administration of which must be supervised by
a parent or guardian], IUD, depot medication or tubal ligation) and have a negative serum
pregnancy test prior to entry into the study.

Subject scores at least "4" (moderately ill) on the Clinical Global Impression-Severity
Scale for Autistic Disorder (CGI-AD).

Subject meets the following criteria at pre-study diagnostic assessment and baseline
assessment: OAS-M 13 or ABC-Irritability Subscale 18 (raw scores).

Subjects with history of seizures, who have been seizure-free for 6 months on a stable dose
of anticonvulsant medication other than divalproex sodium or related formulations (e.g.,
depakene). Non-medicated subjects with a history of seizures who have been seizure-free for
6 months. Subjects with abnormal EEG but no clinical seizures.

State exclusion criteria for enrollment in study:

Subjects who are pregnant or nursing mothers. Sexually active women of childbearing
potential who are not using adequate birth control measures (detailed above in inclusion
criteria).

Subjects with overall adaptive behavior scores below the age of two years on the Vineland
Adaptive Behavior Rating Scale.

Subjects with active or unstable epilepsy.

Subjects with any of the following past or present mental disorders: schizophrenia,
schizoaffective disorder or organic mental disorders.

Subjects who are a serious suicidal risk.

Subjects with clinically significant or unstable medical illness that would contraindicate
participation in the study, including hematopoietic or cardiovascular disease,
pancreatitis, liver toxicity, and polycystic ovary syndrome.

Subjects reporting history of encephalitis, phenylketonuria, tuberous sclerosis, fragile X
syndrome, anoxia during birth, pica, neurofibromatosis, hypomelanosis of Ito,
hypothyroidism, Duchenne muscular dystrophy, and maternal rubella.

Patients with history of the following:

gastrointestinal, liver, or kidney, or other known conditions which will presently
interfere presently with the absorption, distribution, metabolism, or excretion of drugs;
cerebrovascular disease or brain trauma; clinically significant unstable endocrine
disorder, such as hypo- or hyperthyroidism; recent history or presence of any form of
malignancy

Treatment within the previous 30 days with any drug known to a well-defined potential for
toxicity to a major organ

Subjects with clinically significant abnormalities in laboratory tests or physical exam.

Subjects likely to require ECT or any other psychotropic medication during the study,
unless otherwise permitted.

Subjects unable to tolerate taper from psychoactive medication if necessary.

Subjects with a history of hypersensitivity or severe side effects associated with the use
of divalproex sodium, or other an ineffective prior therapeutic trial of divalproex sodium
(serum levels within range of 50-100 ug/ml for 6 weeks).

Subjects who have received any of the following interventions within the prescribed period
before starting treatment:

investigational drugs within the previous 30 days; depot neuroleptic medication;
psychotropic drugs not permitted for concurrent use in the study within the previous seven
days; fluoxetine within the previous five weeks.

Subjects who have begun any new alternative non-medication treatments, such as diet,
vitamins, and psychosocial therapy, within the previous three months.

Subjects with any organic or systemic disease or patients who require a therapeutic
intervention, not otherwise specified, which would confound the evaluation of the safety of
the study medication.

Subjects who reside in a remote geographical area who do not have regular access to
transportation to the clinical facility.