• California Verbal Learning Test [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  

• Rapid Visual Information Processing Task [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  

A large proportion of subjects with bipolar disorder experience significant cognitive dysfunction, even when euthymic, after adequate treatment. The cognitive deficits in asymptomatic patients with bipolar disorder are very important for the subject's psychosocial function. In this population, cognitive deficits have been associated with poor psychosocial functioning, such as inability to hold a job. Memantine is a glutamate NMDA receptor antagonist which has shown efficacy in cognitive dysfunction due to moderate to severe Alzheimer disease.

Demonstrating the role of Memantine in reducing cognitive dysfunction in minimally symptomatic subjects with bipolar disorder promises to provide important clinical information, which could lead to improvements in well-being and functional status for large populations of subjects with bipolar disorder.

Inclusion Criteria:

• DSM-IV diagnostic criteria for any bipolar disorder (type I, type II, and NOS) (diagnosed with the use of the Structured Clinical Interview for DSM-IV-TR Mood Module (SCID Mood Module)
• Written informed consent
• Men or women aged 18-65
• A baseline Hamilton-D 17 score of < 10 at screen and baseline visits.
• A baseline YMRS score of < 10 at screen and baseline visits.
• No acute episodes of depression or mania for the previous 12 weeks.
• MGH Cognitive and Physical Functioning Scale: Cut-off : >15 or Everyday Cognition Self-Report Form: Average of all items >1.5 or RBANS: <12 years education, RBANS total scale score of <85 =12 years education, RBANS total scale score of <93 >12 years education, RBANS total scale score of <100
• Able to read and understand English.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from the study:

• Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment.
• Pregnant women, nursing mothers, or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy).
• Serious or unstable medical illness, including liver impairment, kidney impairment, cardiovascular, hepatic, respiratory, endocrine, neurologic or hematologic disease.
• History of seizure disorder, brain injury, any history of known neurological disease (multiple sclerosis, degenerative disease such as ALS, Parkinson disease and any movement disorders, etc).
• History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months.
• History of multiple adverse drug reactions.
• Patients with mood congruent or mood incongruent psychotic features within the last 12 months.
• Clinical or laboratory evidence of hypothyroidism.
• Patients who have had an episode of acute depression or mania during the 12 weeks prior to enrollment.
• Patients who have had electroconvulsive therapy (ECT) within the 6 months preceding enrollment.
• Patients taking drugs which alkalinize the urine (e.g., carbonic anhydrase inhibitors, sodium