Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00040261
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2002-06-22
Brief Title:
Clinical Trial of Memantine for Major Depression
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Investigation of the Antidepressant Efficacy of Memantine an NMDA Antagonist With Neurotrophic Properties in Major Depression
Status:
COMPLETED
Status Verified Date:
2005-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine the safety and effectiveness of the drug memantine for treating major depression
Major depression is a serious public health concern that contributes to significant morbidity and mortality Despite the availability of a wide range of antidepressant drugs a proportion of patients with major depression fail to respond to first-line antidepressant treatment despite adequate dosage duration and compliance Recent studies suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression Memantine and other agents which reduce glutamatergic neurotransmission may represent a novel class of antidepressants
The study consists of three phases In Phase 1 participants will be tapered off all psychiatric medications over a 2-week washout period In Phase 2 participants will be randomly assigned to receive either memantine or placebo an inactive pill three times a day for 8 weeks Participants who do not respond to the treatment after 8 weeks will be taken off the study and offered standard treatment Weekly psychiatric evaluations will evaluate treatment response During Phase 2 participants who respond well to treatment will enter Phase 3 a 16-week continuation phase of either memantine or placebo Interviews will be conducted every other week in the first month then monthly thereafter
Participants will have a physical examination neuropsychological tests and eye blink tests at baseline and at the end of the study Pulse blood pressure and blood samples will be taken throughout the study Participants will undergo an electrocardiogram as well as positron emission tomography PET and magnetic resonance imaging MRI scans of the brain
Major depression is a serious public health concern that contributes to significant morbidity and mortality Despite the availability of a wide range of antidepressant drugs a proportion of patients with major depression fail to respond to first-line antidepressant treatment despite adequate dosage duration and compliance Recent studies suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression Memantine and other agents which reduce glutamatergic neurotransmission may represent a novel class of antidepressants
The study consists of three phases In Phase 1 participants will be tapered off all psychiatric medications over a 2-week washout period In Phase 2 participants will be randomly assigned to receive either memantine or placebo an inactive pill three times a day for 8 weeks Participants who do not respond to the treatment after 8 weeks will be taken off the study and offered standard treatment Weekly psychiatric evaluations will evaluate treatment response During Phase 2 participants who respond well to treatment will enter Phase 3 a 16-week continuation phase of either memantine or placebo Interviews will be conducted every other week in the first month then monthly thereafter
Participants will have a physical examination neuropsychological tests and eye blink tests at baseline and at the end of the study Pulse blood pressure and blood samples will be taken throughout the study Participants will undergo an electrocardiogram as well as positron emission tomography PET and magnetic resonance imaging MRI scans of the brain
Detailed Description:
Major affective disorders are common severe chronic and often a life-threatening illness Major depression contributes to significant morbidity and mortality Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses Suicide is the cause of death in 10-20 of individuals with recurrent depressive disorders
Despite the availability of a wide range of antidepressant drugs clinical trials indicate that 30 to 40 of patients with major depression fail to respond to first-line antidepressant treatment despite adequate dosage duration and compliance Thus there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system Furthermore a growing body of data suggests that mood disorders are associated with regional volumetric reductions and cell loss and atrophy It is thus noteworthy that lamotrigine which among other effects reduces glutamate release has antidepressant effects and a pilot study has suggested that NMDA antagonists may have antidepressant effects Together this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression and that agents which more directly reduce glutamatergic neurotransmission may represent a novel class of antidepressants
Memantine Akatinol memantine an agent that is approved in Germany for dementia syndrome Parkinsons disease has significant antiglutamatergic and neuroprotective properties may prove to have antidepressant properties in depressed patients In this study we propose to investigate the potential efficacy of memantine an agent which reduces glutamatergic output via open-channel block of the NMDA receptor-associated ion channel Most importantly memantine only blocks the channel during periods of abnormal excessive activity and leaves relatively spared normal neurotransmission This finding is the basis for the minimal side effect profile displayed by memantine
Patients ages 18 to 80 with a diagnosis of major depression without psychotic features will be randomized to double-blind treatment outpatient study to receive either memantine 5-20mgday or placebo for a period of 8 weeks Following this acute period patients who fully respond could enter a 16-week continuation phase Acute efficacy will be determined by demonstrating a greater response rate using specified criteria Approximately 112 patients with acute major depression will be enrolled in the study
Despite the availability of a wide range of antidepressant drugs clinical trials indicate that 30 to 40 of patients with major depression fail to respond to first-line antidepressant treatment despite adequate dosage duration and compliance Thus there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system Furthermore a growing body of data suggests that mood disorders are associated with regional volumetric reductions and cell loss and atrophy It is thus noteworthy that lamotrigine which among other effects reduces glutamate release has antidepressant effects and a pilot study has suggested that NMDA antagonists may have antidepressant effects Together this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression and that agents which more directly reduce glutamatergic neurotransmission may represent a novel class of antidepressants
Memantine Akatinol memantine an agent that is approved in Germany for dementia syndrome Parkinsons disease has significant antiglutamatergic and neuroprotective properties may prove to have antidepressant properties in depressed patients In this study we propose to investigate the potential efficacy of memantine an agent which reduces glutamatergic output via open-channel block of the NMDA receptor-associated ion channel Most importantly memantine only blocks the channel during periods of abnormal excessive activity and leaves relatively spared normal neurotransmission This finding is the basis for the minimal side effect profile displayed by memantine
Patients ages 18 to 80 with a diagnosis of major depression without psychotic features will be randomized to double-blind treatment outpatient study to receive either memantine 5-20mgday or placebo for a period of 8 weeks Following this acute period patients who fully respond could enter a 16-week continuation phase Acute efficacy will be determined by demonstrating a greater response rate using specified criteria Approximately 112 patients with acute major depression will be enrolled in the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-M-0231 | None | None | None |