Depressive Disorder, Major
Conditions
Brief summary
The purpose of this study is to determine whether taking the medication memantine reduces impairment of memory and attention associated with electroconvulsive therapy.
Detailed description
The primary objective of this study is to determine whether the novel NMDA antagonist memantine, FDA approved for use in moderate to severe alzheimers dementia, may reduce the neurocognitive deficits associated with right unilateral ECT treatments in patients receiving ECT for a severe and relatively refractory Major Depressive episode. Our hypothesis is that the use of an NMDA antagonist would reduce intracellular calcium levels, and glutamatergic stimulation during ECT. This reduction in excitatory stimulation during ECT would reduce hippocampal and prefrontal neuronal endangerment and dysfunction, thereby reducing cognitive impairment associated with right unilateral ECT treatments. We also hypothesize that ACTH and cortisol levels will correlate with neurocognitive impairment in placebo treated subjects, but not in the memantine treated individuals.
Interventions
DRUGmemantine
Patients received a memantine containing capsule starting the day before ECT begins and while receiving ECT
DRUGPlacebo Oral Capsule
Patients received a placebo capsule starting the day before ECT begins and while receiving ECT
Sponsors
Forest Laboratories
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
: * Meets DSM-IV criteria for Major Depressive Disorder * 18 to 75 years of age and able to provide legal consent * Referred to Stanford ECT service by treating physician for unilateral electroconvulsive therapy with inpatient hospitalization * Competed process for consenting to the clinical use of ECT according to California State law * Females of childbearing potential will be required to use a double-barrier method of contraception, which includes foam and either condom and diaphragm, IUD, and/or implant during study.
Exclusion criteria
- Treatment with ECT in the 6 months prior to screening * Meets criteria for drug or alcohol abuse or dependence in the 6 months prior to screening * Use of alcohol or illegal drugs within seven days of randomization or during study. Patients may be excluded for use during a period greater than 7 days, per study physician's discretion * Presence of unstable or untreated cardiovascular disease, hypertension, or endocrine disorder as determined by the investigator * use of antipsychotic, antidepressant, or other prescription medications unless dose is stable for at least 7 days prior to randomization. * Use of any investigational treatment within 30 days of randomization * Previous allergic reaction to memantine or drugs of similar chemical structure. * Women who are pregnant or breastfeeding are not advised to participate in the research study * Any neurological disorder or organic brain condition that would confound neurocognitive testing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Memantine Effect on CVLT Long Term Recall After Right Unilateral ECT Treatment. | 30 days | The California Verbal Learning Test Delayed Free Recall is a measure of episodic verbal learning and memory. These results are from the Free Recall subtest. In this test the subject must recall a list of 16 nouns after 20 minutes without cueing. It assesses auditory encoding, recall and recognition. Scores reflect the number of correct recall of the presented words, and scores are are then normalized by age. A higher score reflects better memory function. |
Countries
United States
Participant flow
Recruitment details
Patients over age 18 who are referred for ECT for unipolar or bipolar depression were screened and enrolled. All patients receive right unilateral lead placements, and otherwise the entire procedure would be delivered as per usual clinical care at our institution. Patients who sign an informed consent for this study were screened for eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Memantine Patients receive memantine starting the day before ECT begins and while receiving ECT
memantine: Memantine vs placebo | 6 |
| Placebo Patients receive placebo starting the day before ECT begins and while receiving ECT
memantine: Memantine vs placebo | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Placebo | Total | Memantine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 11 Participants | 6 Participants |
| Age, Continuous | 42.5 years STANDARD_DEVIATION 11.3 | 41.0 years STANDARD_DEVIATION 11.9 | 39.3 years STANDARD_DEVIATION 13.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 6 Participants |
| Region of Enrollment United States | 5 participants | 11 participants | 6 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
Memantine Effect on CVLT Long Term Recall After Right Unilateral ECT Treatment.
The California Verbal Learning Test Delayed Free Recall is a measure of episodic verbal learning and memory. These results are from the Free Recall subtest. In this test the subject must recall a list of 16 nouns after 20 minutes without cueing. It assesses auditory encoding, recall and recognition. Scores reflect the number of correct recall of the presented words, and scores are are then normalized by age. A higher score reflects better memory function.
Time frame: 30 days
Population: The subjects enrolled in the study had signed a consent to receive ECT treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Memantine Effect on CVLT Long Term Recall After Right Unilateral ECT Treatment. | 10.17 units on a scale | Standard Deviation 5.565 |
| Placebo | Memantine Effect on CVLT Long Term Recall After Right Unilateral ECT Treatment. | 6.67 units on a scale | Standard Deviation 4.59 |
p-value: 0.006Regression, Linear