The primary objective of the study is to assess the efficacy and tolerability of a 12-week trial of memantine hydrochloride administered twice daily in 20 adults (ages 18-55) with ADHD and ADHD NOS. Improvement will be defined as: 1) changes from baseline on the investigator-rated DSM-IV based ADHD Rating Scale; 2) changes from baseline in a questionnaire aimed at assessing executive functions (BRIEF); and 3) changes from screening in a computerized neuropsychological battery (CANTAB). We hypothesize that memantine hydrochloride will be associated with improving ADHD symptoms and associated deficits in executive functions. We also expect that memantine will be well-tolerated with predictable adverse events.

Memantine (Namenda) is a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist believed to work by blocking prolonged low-level activation of the NMDA receptor and resultant neuronal damage caused by abnormal glutamatergic activity, yet also allowing normal physiological activity of the NMDA channel. Memantine (Namenda) was approved by the U.S. Food and Drug Administration in 2003 for the treatment of moderate to severe Alzheimer's disease. Memantine improves or delays the decline in cognition (attention, language, visuo-spatial ability), as well as functional and behavioral symptoms in adults with moderate Alzheimer's disease.

Although the efficacy and safety of memantine has not been tested in people with ADHD, the spectrum of disorders possibly amenable to NMDA receptor antagonist treatment may include ADHD and associated executive function deficits (EFDs). To this end, we are proposing an open-label pilot study of memantine in adult subjects with ADHD and ADHD Not Otherwise Specified (NOS).

This will be a 12-week, open-label pilot study to assess the efficacy and tolerability of memantine hydrochloride (Namenda) administered to 20 adults 18-55 years of age with ADHD and ADHD NOS. All subjects that enter the study will undergo standard screening and diagnostic procedures. After obtaining written informed consent from the subject, the diagnosis of ADHD will be established through clinical evaluation by an expert clinician. Only consenting subjects satisfying inclusion and exclusion criteria will be included in the study.

Inclusion Criteria:

1. Male and female outpatients 18-55 years of age
2. Subjects with the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), by DSM-IV or ADHD NOS (late onset; >7 years), as manifested in clinical evaluation and confirmed by structured interview.
3. Subjects must score at least 14 on inattentive symptom questions on the DSM-IV based ADHD Rating Scale.
4. Subjects who have an ADHD specific CGI Severity score of 4 or more (> moderately impaired).

Exclusion Criteria:

1. Subjects with a medical condition or treatment that will either jeopardize subject safety or affect the scientific merit of the study, including:
2. History of Renal or Hepatic Impairment.
3. Organic brain disorders.
4. History of Seizure disorder.
5. Any clinically unstable psychiatric conditions including the following: psychosis, suicidality, bipolar disorder, current substance use disorders (alcohol or drugs) or current tic disorder.
6. Mental retardation (IQ <75).
7. Pregnant or nursing females.
8. Known hypersensitivity to memantine.
9. Any current psychotropic treatment, with the exception of stable regimen of SSRIs.