This study will attempt to study the effect of memantine, on memory, and motor praxis/expressive language skills in children with autism.

The investigators will recruit children ages 6-12 years who are verbal and meet criteria for Autism Spectrum Disorder. The children will be assessed for memory function, expressive language output and motor skills/praxis. They will then be randomized to memantine or placebo for 6 months. The effects of this medication and its safety in this population will be studied over the 6 month period.

Abnormalities in the modulation of the glutamate system have been reported by multiple investigators studying animal models, post-mortem brains, and single gene disorders that have overlapping phenotypes with autism. Abnormalities in glutamatergic function have been reported in disorders affecting a variety of behavioral and neurological domains, from mood stability, to cognitive flexibility, memory, and motor function. Numerous studies have reported a variety of memory and motor deficits in children with autism. Whereas the neurobiology of such deficits is an area of active research, there is a paucity of intervention research for such deficits in autism. This study will attempt to study the effect of an N-methyl-D-aspartate receptor (NMDA) inhibitor, memantine, on memory, and motor praxis/expressive language skills in children with autism.

Methods: Children ages 6-12 years who are verbal and meet criteria for Autism Spectrum Disorder will be recruited across 2 sites. After consent, the children will be assessed for memory function, expressive language output and motor skills/praxis. They will then be randomized 1:1 to memantine versus placebo for 6 months. The effects of this medication on the above mentioned symptoms domains as well as its safety in this population will be studied over the 6 month period.

Inclusion Criteria

1. Male or female outpatients 6 to 12 years of age
2. Verbal; Module 2 or 3 on Autism Diagnostic Observation Schedule (ADOS)
3. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) for Autism Spectrum Disorder. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised (ADI-R) and ADOS Module 2 or 3.
4. Parents report difficulties with motor skills
5. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening and Baseline
6. If already receiving stable nonpharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study
7. Participants can be on up to 2 concomitant psychotropic medications before entering the study, provided that they have been on a stable dose for 30 days and have no plans to adjust the dose for the duration of study
8. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators
9. Prior to the conduct of any study-specific procedures, the patient must provide assent to participate in the study (if developmentally appropriate), and the parent or legal guardian must provide written informed consent
10. The patient and the patient's parent or legal guardian must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments
11. The parent or legal guardian must be capable of providing reliable information about the patient's condition, agree to oversee the administration of study drug, and accompany the patient to all clinic visits

Exclusion Criteria:

1. Patients born prior to 35 weeks gestational age
2. Patients with any primary psychiatric diagnosis other than autism at Screening: a history of Attention Deficit Hyperactivity Disorder (ADHD), bipolar disorder, psychosis, post-traumatic stress disorder, schizophrenia, or major depressive disorder
3. Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal MRI/structural lesion of the brain
4. Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
5. Patients who plan to initiate or change pharmacological or nonpharmacologic interventions during the course of the study
6. Patients on d-cycloserine or riluzole as they both target the glutamate system
7. Patients on agents that alkalinize the urine (acetazolamide, potassium citrate, and sodium bicarbonate), as they decrease the elimination of memantine
8. Patients who have received treatment with memantine in the past with no response
9. Patients with a history of hypersensitivity reaction to dextromethorphan, amantadine, or any other NMDA receptor antagonists
10. Patients unable to tolerate venipuncture procedures for blood sampling
11. Patients who, in the Investigator's opinion, might not be suitable for the study
12. Children weighing under 20 kg (to meet FDA approvals)
13. Patients with a positive pregnancy test