Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Controlled Study of Olanzapine in Children With Autism
Brief Summary: This is a 12-week study which investigates the use of olanzapine to decrease disruptive behaviors sometimes associated with Autism in children, aged 3 to 12 years old. The first six weeks of the study are double-blind and placebo controlled, meaning that patients receive either placebo or olanzapine, and that neither the researchers nor the patients know whether or not they are receiving placebo or olanzapine. In the second six weeks all of the patients receive olanzapine. The purpose in using placebo is that it is otherwise impossible to know how effective the drug is or whether or not the drug causes side effects. Patients treated with placebo can have improvement and can have side effects. In the study patients receive a psychiatric evaluation, physical examination, laboratory tests, and study medication (olanzapine or placebo), free of charge.


Options:
A: Inclusion Criteria:

* Male and Female
* 18 to 55 years old
* Meet Diagnostic and Statistical Manual-IV (DSM-IV), Autism Diagnostic Observation Schedule(ADOS), and Autism Diagnostic Interview-Revised (ADI-R) standards for Autism Spectrum Disorder or Aspergers Syndrome
* Have a high, normal or near normal Intelligent Quotient
* Speak and Understand English fluently

Exclusion Criteria:

* Born prior to 35 weeks gestational age
* Any primary psychiatric diagnosis other than autism at the time of screening
* Medical history of neurological disease
* Medical history of known MRI/structural lesion of the brain
* Patients who are pregnant
* With a medical condition that might interfere with the conduct of the study, confound interpretation of study results or endanger their own well being
* With evidence or history of malignancy or any significant hematological, endocrine, cardiovascular, respiratory, renal, hepatic or gastrointestinal disease
* Taking psychoactive medications
* Who plan to initiate or change nonpharmacologic interventions during the study course
* Who are unable to tolerate venipuncture procedures for blood sampling
B: Inclusion Criteria:

Autism/ADHD Group:

* DSM-IV diagnosis of autistic disorder, as per the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS)
* Child manifests current symptoms of ADHD

Autism/non-ADHD Group:

* Meets the diagnostic criteria for autism, as above, but does not meet the diagnostic criteria for ADHD

Exclusion Criteria:

In both groups, exclusion criteria will include:

* Sensory or motor deficits sufficient to interfere with testing (e.g., blindness, severe cerebral palsy)
* Serious neurological disorders (e.g., epilepsy, stroke)
* Down syndrome, fragile X syndrome, Tourette syndrome, or fetal alcohol syndrome
* Bipolar disorder or a family history of bipolar disorder in a first-degree relative
* Other serious psychopathology that resulted in psychiatric hospitalization (e.g., for psychotic episode). The investigators will screen for this using the Diagnostic Interview for Children and Adolescents (DICA)-IV, and getting a complete developmental/medical history
* Serious physical handicaps that would interfere with performance on laboratory tasks
* IQ less than 50 and greater than 130
* Verbal mental age (VMA) less than 36 months (to exclude participants unable to understand simple task instructions)

In the autism/ADHD group, further exclusion criteria apply to the MPH trial:

* History of intolerance to MPH
* Weight less than 20 kg or greater than 59 kg (less than 44 pounds or greater than 130 pounds)
* Concomitant use of dextroamphetamine preparations (Dexedrine, Dextrostat), mixed amphetamine salts (Adderall XR), other MPH preparations (e.g., Concerta, Metadate); venlafaxine, bupropion, atomoxetine, guanfacine, modafinil.
* Concomitant use of any herbal preparations
* Medical condition for which stimulants are contraindicated (e.g., high blood pressure)
* Past treatment failure on a methylphenidate trial
C: Inclusion Criteria:

1. Males and females, Aged between 3 and 12 years.
2. Autistic disorder - DSM-IV criteria.
3. A score of at least moderately impaired on the CGI-Severity item.
4. Clinical judgment that medication treatment for autism is indicated.

Exclusion Criteria:

1. Rett's disorder, childhood disintegrative disorder, Asperger's disorder, and PDD, NOS.
2. Psychotic disorder (DSM-IV) (including schizophreniform disorder and schizophrenia).
3. Major depressive disorder (DSM-IV).
4. Bipolar disorder (DSM-IV).
5. History of psychoactive drug in the previous 2 weeks prior to phase 1.
6. A history of treatment with olanzapine for a cumulative period of greater than 2 weeks prior to entering phase 1.
7. Systemic diseases such as cardiac, renal, thyroid diseases, uncontrolled seizure disorder (seizure disorder that is not controlled by anti-epileptic medication - a child who is seizure free for a period of 6 months on a stable dose of antiepileptic drug would be considered controlled), or diabetes mellitus.
8. Children with a known medical cause for autistic disorder.
9. Abnormal fasting blood glucose or history of diabetes.
10. Baseline body mass index (BMI) greater than the 90th percentile for age and gender (CDC growth charts, Kuczmarski et al, 2000) (because of risk of weight gain).
11. Baseline QTc \>450 msec. Note: Historically, patients we evaluate do not have QTc values \>450.
12. Dyskinesias at baseline (per the criteria of Schooler and Kane, 1982).
D: INCLUSION CRITERIA

All Participants:

1. Male and female participants, ages 8-17 years (inclusive)

   Participants with Autism Spectrum Disorder:
2. Meets Diagnostic and Statistical Manual-5 autism spectrum disorder diagnostic criteria, as established by clinical diagnostic interview
3. At least moderate severity of social impairment, as measured by a total raw score of ≥85 on the parent/guardian-completed Social Responsiveness Scale, Second Edition (SRS-2) and a score of ≥4 on the clinician-administered Autism Spectrum Disorder Clinical Global Impression-Severity scale (ASD CGI-S)

Healthy Control Participants:

2. Age-, sex-, and IQ-matched with participants with autism spectrum disorder 3. No Axis I diagnoses, as established by the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version (K-SADS-E) and confirmed by clinical diagnostic interview 4. No significant traits of autism spectrum disorder, as measured by a total raw score of \<60 on the parent/guardian-completed Social Responsiveness Scale, Second Edition

EXCLUSION CRITERIA

All Participants:

1. IQ ≤70 based, on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) Vocabulary and Matrix Reasoning subtests
2. Impaired communicative speech
3. Current treatment with the following medications, which are known to impact glutamate levels:

   1. Lamotrigine
   2. Amantadine
   3. N-acetylcysteine
   4. D-cycloserine
4. Current treatment with a psychotropic medication, not listed above, on a dose that has not been stable for at least 4 weeks prior to study baseline
5. Co-administration of drugs that compete with memantine for renal elimination using the same renal cationic system, including hydrochlorothiazide, triamterene, metformin, cimetidine, ranitidine, quinidine, and nicotine
6. Initiation of a new psychosocial intervention within 30 days prior to randomization
7. Participants who are pregnant and/or nursing
8. Participants with a history of non-febrile seizures without a clear and resolved etiology
9. Participants with a history of or a current liver or kidney disease
10. Clinically unstable psychiatric conditions or judged to be at serious suicidal risk
11. Participants who meet for alcohol or drug dependence or abuse on the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version. If the participant has a recent history of substance abuse, as an added precaution, there will be a 2-week washout period before initiating the trial. There are no known safety issues relating to memantine and recent history of substance abuse.
12. Serious, stable or unstable, systemic illness, including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
13. Participants with severe hepatic impairment (Liver Function Tests \[LFTs\] \>3 times the Upper Limit of Normal \[ULN\])
14. Participants with genitourinary conditions that raise urine Power of Hydrogen (pH) (e.g., renal tubular acidosis, severe infection of the urinary tract)
15. Known hypersensitivity to memantine
16. Severe allergies or multiple adverse drug reactions
17. A non-responder or history of intolerance to memantine after treatment at adequate doses, as determined by the clinician
18. Investigator and his/her immediate family, defined as the Investigator's spouse, parent, child, grandparent, or grandchild.

Answer: C