Memantine is a glutamate NMDA receptor antagonist which has shown efficacy in cognitive
dysfunction due to moderate to severe Alzheimer disease (Reisberg et al., 2003).
The investigators propose to treat 75 subjects with bipolar disorder with minimal mood
symptoms and cognitive dysfunction with memantine or placebo. The 75 subjects will be
enrolled at three sites. The same study will be performed at all three sites, with each site
functioning independently of the other.
The investigators study will include objective neuropsychological testing of memory and
executive functions before and after treatment, as well as ratings of mood symptoms and
subjective patient ratings of memory function at every study visit.
The principal aim of this study is to measure the efficacy of memantine on improving memory
function in minimally symptomatic subjects with bipolar disorder. The investigators
hypothesize that in minimally symptomatic subjects with bipolar disorder memantine will be
efficacious in improving cognitive functions, as measured by the difference in
neuropsychological test scores at the beginning and at the end of the trial.
Secondary analyses will test the role of memantine in improving residual mood symptoms
(depression and mania) in subjects with bipolar disorder.
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.
There will be an optional open label 12-week extension to the study. Subjects will be
restarted on memantine similar to the regimen in the first phase of the study. Subjects will
meet with the investigators every four weeks (weeks 16, 20, and 24) for assessment as
mentioned above. Neuropsychological testing will be repeated at week 24. It is the
investigator's belief that this added timeline will better demonstrate any improvements in
cognitive function.
Screen: Week - 2; Baseline Visit: Week 0; Visit 1Week 4; Visit 2Week 8;Visit 3Week 12
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Inclusion Criteria:
Inclusion criteria: the following conditions must be met for patient eligibility:
- 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 orRBANS:
- <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 bicarbonate)