Memantine and Cognitive Dysfunction in Bipolar Disorder

A large proportion of participants 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 participant'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
N-methyl-D-aspartate (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 participants with bipolar disorder promises to provide important clinical
information, which could lead to improvements in well-being and functional status for large
populations of participants with bipolar disorder.

Inclusion Criteria:

- Diagnostic and Statistical Manual-IV (DSM-IV) diagnostic criteria for any bipolar
disorder [type I, type II, and not otherwise specified (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 Young Mania Rating Scale score of < 10 at screen and baseline visits.

- No acute episodes of depression or mania for the previous 12 weeks.

- Massachusetts General Hospital Cognitive and Physical Functioning Scale: Cut-off: >15
or Everyday Cognition Self-Report Form: Average of all items >1.5 or Repeatable
Battery for the Assessment of Neuropsychological Status (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:

- Participants 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, intrauterine device (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 amyotrophic lateral sclerosis (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.