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| Name | Class |
|---|---|
| Forest Laboratories | INDUSTRY |
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This study is evaluating the efficacy and safety of the drug memantine (trade name NAMENDA) as an augmentation agent for the treatment of depression in people who are not fully responding to antidepressant medications.
- Objective
The objective of this study is to evaluate the efficacy and safety of 20 mg of memantine administered once daily as an augmentation agent for subjects who have been taking antidepressants for at least 1 month but who have experienced an incomplete or absent therapeutic response.
- Background
Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that is approved for the treatment of moderate-to-severe dementia of the Alzheimer's type. It has been commercially available in 23 countries worldwide since 1982.
There are reports in the published literature that suggest NMDA receptors may be involved in the etiology of depressive disorders. The NMDA antagonist ketamine has been shown to have antidepressant effects in a placebo-controlled clinical trial (Berman et al., 2000). Uncompetitive NMDA receptor antagonists, including memantine, have been shown to exhibit antidepressant-like activity in animal models of depression (Moryl et al., 1993, Papp and Moryl 1994). Animal studies also support the possibility that uncompetitive NMDA receptor antagonists may work synergistically in combination with antidepressants in animal models of depression (Rogoz et al., 2001). Some authors have hypothesized a role for NMDA receptors in the therapeutic effects of numerous antidepressants (Skolnick et al., 1996).
- Study Design and Duration
This is a randomized, single site, double-blind, placebo-controlled, parallel-group study in outpatients. The study consists of an 8-week double-blind treatment period. Approximately 25 patients will be randomized to each treatment group (memantine or placebo) for a total of approximately 50 patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| memantine | Experimental | memantine (5-20mg a day) |
|
| Placebo | Placebo Comparator | placebo (5-20mg a day) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| memantine | Drug | memantine 5mg - 20mg PO daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Montgomery-Asberg Depression Rating Score (MADRS) | Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Scores 0 to 6 indicate symptoms absent; 7 to 19 indicates mild depression; 30 to 34 defines moderate; 35 to 60 indicates severe depression. Changes in MADRS score was a primary measure. | Baseline & week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Modified Quick Inventory of Depressive Symptoms Self Report Scale (QIDS-SR) | The 16 item Quick Inventory of Depressive Symptomatology (QIDS-SR16) (Rush et al. 2003) is designed to assess the severity of depressive symptoms, with higher scores representing more severe forms of depression. When complete, the QIDS are scored by summing responses to obtain a total score ranging from 0 to 27. Either appetite increase or decrease, but not both, are used to calculate the total score. Weight increase or decrease, but not both, are used to calculate the total score. Scores 0-5 indicate no severity of depression; 6-10 is mild; 11-15 is moderate; 16-20 is severe; 21-27 is very severe levels of depression. Participants were evaluated at baseline and at weeks 1, 2, 3, 4, 6 & 8. |
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Inclusion Criteria:
Male or female patients between 18 and 85 years of age at screening.
Patients must provide written informed consent prior to study entry.
Patients must meet DSM-IV-TR (Diagnostic and Statistical Manual IV Text Revision) criteria for Major Depressive Episode of a severity mild, moderate or severe or in partial remission, as confirmed by the MINI.
Patients must have a HAM-D (17-item) score of 16 or higher.
Patients must have been on 1 of the following medications for 4 or more weeks at or above the listed dose with no psychiatric medication dose changes for the past 25 days:
Participants must agree to keep the dose of their existing antidepressant(s) constant throughout the 8-week trial.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kristina M Deligiannidis, M.D. | University of Massachusetts, Worcester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Psychopharmacologic Research and Treatment (University of Massachusetts Medical School) | Worcester | Massachusetts | 01605 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10686270 | Background | Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9. | |
| 8361950 | Background | Moryl E, Danysz W, Quack G. Potential antidepressive properties of amantadine, memantine and bifemelane. Pharmacol Toxicol. 1993 Jun;72(6):394-7. doi: 10.1111/j.1600-0773.1993.tb01351.x. |
| Label | URL |
|---|---|
| Center for Psychopharmacologic Research and Treatment | View source |
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Participants continued on their previously prescribed antidepressant at the same dose throughout the study.
Study participants were recruited through clinician referral and posted and radio advertising with the majority of patients recruited through clinician referral within our single-site, tertiary-care medical center.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo comparator : 5mg - 20mg PO daily over 8 weeks |
| FG001 | Memantine | memantine : memantine 5mg - 20mg PO daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo comparator : 5mg - 20mg PO daily over 8 weeks |
| BG001 | Memantine | memantine : memantine 5mg - 20mg PO daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Montgomery-Asberg Depression Rating Score (MADRS) | Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Scores 0 to 6 indicate symptoms absent; 7 to 19 indicates mild depression; 30 to 34 defines moderate; 35 to 60 indicates severe depression. Changes in MADRS score was a primary measure. | The primary outcome examines a mean change in MADRS scores at baseline & week 8 through last observation carried forward (LOCF); no values were imputed for missing assessments. The primary data analysis used intent-to-treat measures and computes final study score minus baseline averaged among participants to evaluate treatment group differences. | Posted | Mean | Standard Deviation | units on a scale | Baseline & week 8 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo comparator : 5mg - 20mg PO daily over 8 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| anxiety | Psychiatric disorders | Systematic Assessment |
Early termination due to slow enrollment, leading to small numbers of subjects enrolled.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kristina Deligiannidis | UMass Medical School | 508-856-5928 | kristina.deligiannidis@umassmemorial.org |
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| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D008559 | Memantine |
| ID | Term |
|---|---|
| D000547 | Amantadine |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo | Drug | 5mg - 20mg PO daily over 8 weeks |
|
| baseline & week 8 |
| Hamilton Anxiety Rating Scale (HARS) | Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Scores > 30 indicate severe anxiety. | baseline & week 8 |
| Montgomery-Asberg Depression Rating Score (MADRS) | Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6 on 10 items. The overall score ranges from 0 to 60. Scores 0 to 6 indicate symptoms absent; 7 to 19 indicates mild depression; 30 to 34 defines moderate; 35 to 60 indicates severe depression. Changes in response rate and remission rate were assessed for secondary measures. | baseline and week 8 |
| 12934985 | Background | Oquendo MA, Baca-Garcia E, Kartachov A, Khait V, Campbell CE, Richards M, Sackeim HA, Prudic J, Mann JJ. A computer algorithm for calculating the adequacy of antidepressant treatment in unipolar and bipolar depression. J Clin Psychiatry. 2003 Jul;64(7):825-33. doi: 10.4088/jcp.v64n0714. |
| 7821340 | Background | Papp M, Moryl E. Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression. Eur J Pharmacol. 1994 Sep 22;263(1-2):1-7. doi: 10.1016/0014-2999(94)90516-9. |
| 15156068 | Background | Rogoz Z, Skuza G, Kusmider M, Wojcikowski J, Kot M, Daniel WA. Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies. Pol J Pharmacol. 2004 Mar-Apr;56(2):179-85. |
| 8852530 | Background | Skolnick P, Layer RT, Popik P, Nowak G, Paul IA, Trullas R. Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry. 1996 Jan;29(1):23-6. doi: 10.1055/s-2007-979537. |
| 34510411 | Derived | Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3. |
| 24229746 | Derived | Smith EG, Deligiannidis KM, Ulbricht CM, Landolin CS, Patel JK, Rothschild AJ. Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2013 Oct;74(10):966-73. doi: 10.4088/JCP.12m08252. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Memantine | memantine : memantine 5mg - 20mg PO daily |
|
|
| Secondary | Modified Quick Inventory of Depressive Symptoms Self Report Scale (QIDS-SR) | The 16 item Quick Inventory of Depressive Symptomatology (QIDS-SR16) (Rush et al. 2003) is designed to assess the severity of depressive symptoms, with higher scores representing more severe forms of depression. When complete, the QIDS are scored by summing responses to obtain a total score ranging from 0 to 27. Either appetite increase or decrease, but not both, are used to calculate the total score. Weight increase or decrease, but not both, are used to calculate the total score. Scores 0-5 indicate no severity of depression; 6-10 is mild; 11-15 is moderate; 16-20 is severe; 21-27 is very severe levels of depression. Participants were evaluated at baseline and at weeks 1, 2, 3, 4, 6 & 8. | The secondary outcome examines a change over in mean QID-SR scores at baseline & week 8 through last observed data carried forward (LOCF); no values were imputed for missing assessments. Data analysis used intent-to-treat measures and computes final study score minus baseline averaged among participants to evaluate treatment group differences. | Posted | Mean | Standard Deviation | units on a scale | baseline & week 8 |
|
|
|
| Secondary | Hamilton Anxiety Rating Scale (HARS) | Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Scores > 30 indicate severe anxiety. | Secondary outcome examines a change in mean HARS scores observed at baseline & week 8 through last observed data carried forward (LOCF);no values were imputed for missing assessments.Efficacy data analysis used intent-to-treat measures & computes final study score minus baseline averaged among participants to evaluate treatment group differences | Posted | Mean | Standard Deviation | units on a scale | baseline & week 8 |
|
|
|
| Secondary | Montgomery-Asberg Depression Rating Score (MADRS) | Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6 on 10 items. The overall score ranges from 0 to 60. Scores 0 to 6 indicate symptoms absent; 7 to 19 indicates mild depression; 30 to 34 defines moderate; 35 to 60 indicates severe depression. Changes in response rate and remission rate were assessed for secondary measures. | Secondary outcome examines a change in response rates,when 50% change from baseline, & remission rates, when MADRS scores of 12 or less were observed.Fischer exact tests assessed efficiency in each treatment group. Intent-to-treat rates at baseline minus week 8 through last observed data carried forward (LOCF) were used;no data values were imputed | Posted | Mean | Standard Deviation | units on a scale | baseline and week 8 |
|
|
|
| 1 |
| 16 |
| 3 |
| 16 |
| EG001 | Memantine | memantine : memantine 5mg - 20mg PO daily | 1 | 15 | 3 | 15 |
| irritability | Psychiatric disorders | Systematic Assessment |
|
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| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |