Depressive DisorderPhase 4NCT00344682
Memantine Augmentation of Antidepressants
A Phase 4 study testing memantine in people with Depressive Disorder, run by University of Massachusetts, Worcester at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Depressive Disorder
- What is being tested?
- memantine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Dec 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 20 mg qD of fluoxetine (Once Daily)
Show all 16Show fewer
- 50 mg qD of sertraline
- 20 mg qD of paroxetine
- 200 mg qD of fluvoxamine
- 20 mg qD of citalopram
- 10 mg qD of escitalopram
- 150 mg qD of venlafaxine or venlafaxine sustained release
- 300 mg qD of bupropion or bupropion sustained or extended release
- 15 mg qD of mirtazapine
- 60 mg qD of duloxetine
- Participants must agree to keep the dose of their existing antidepressant(s) constant throughout the 8-week trial.
Who cannot join
- Diagnosis of bipolar disorder or schizophrenic or schizoaffective disorder.
- History of alcohol or drug abuse or dependence within 6 months of enrollment.
- Patients who have received ECT (Electroconvulsive Therapy) in the past 3 months.
- History of seizures.
- Moderate dementia (MMSE score of 20 or less).
- Active suicidal ideation: endorsing a 3 (most severe score) on QIDS-SR (Quick Inventory of Depression Symptomatology Self Reports) suicide item OR a score of 2 or higher for the past week on Suicide Scale items 4 or 5 (current suicidal ideation moderate or strong or would avoid taking steps to save life).
- Currently taking a mood stabilizer or antipsychotic (except lithium clearly used as an augmenting agent).
- Patients who, in the opinion of the investigator, might not be suitable for the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Psychopharmacologic Research and Treatment (University of Massachusetts Medical School)
Worcester, Massachusetts, 01605
About this study
Official title: A Randomized Double-Blind Pilot Study of Memantine Augmentation in Antidepressant Nonresponders or Incomplete Responders
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.
Read the detailed description
- 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.
- Conditions
- Depressive Disorder
- Being tested
- memantine, Placebo
- Keywords
- memantine, Namenda, augmentation, add-on, depression, MDD (major depressive disorder), unipolar depression, NMDA, ketamine, uncompetitive NMDA receptor antagonist
- Medical subject headings
- Depressive Disorder, Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
memantineDrug
Also called Namenda
memantine 5mg - 20mg PO daily
PlaceboDrug
5mg - 20mg PO daily over 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| memantine | Experimental | memantine (5-20mg a day) Receives: Drug: memantine |
| Placebo | Placebo comparator | placebo (5-20mg a day) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline & week 8
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: baseline and week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2006 (estimated)
- Study startJun 2006
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor
- Investigators
- Kristina M Deligiannidis, M.D., Principal investigator, University of Massachusetts, Worcester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00344682
- Sponsor's protocol ID
- NAM-MD-34
- Status last verified
- Jun 2018
- First submitted
- 22 Jun 2006
- Last updated
- 11 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 10686270Moryl 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.
PubMed 8361950Oquendo 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.
PubMed 12934985Papp 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.
PubMed 7821340Rogoz 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.
PubMed 15156068Skolnick 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.
PubMed 8852530Dean 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.
PubMed 34510411Smith 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.
PubMed 24229746
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind Pilot Study of Memantine Augmentation in Antidepressant Nonresponders or Incomplete Responders
- ClinicalTrials.gov ID
- NCT00344682
- Acronym / sponsor ID
- NAM-MD-34
- Conditions
- Depressive Disorder
- Keywords
- memantine, Namenda, augmentation, add-on, depression, MDD (major depressive disorder), unipolar depression, NMDA
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Jun 2006
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 27 Jun 2006 (estimated)
- Results
- Posted 25 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| memantine | Experimental | Drug: memantinememantine (5-20mg a day) |
| Placebo | Placebo comparator | Drug: Placeboplacebo (5-20mg a day) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
Key exclusion criteria (8 listed)
- Diagnosis of bipolar disorder or schizophrenic or schizoaffective disorder.
- History of alcohol or drug abuse or dependence within 6 months of enrollment.
- Patients who have received ECT (Electroconvulsive Therapy) in the past 3 months.
- History of seizures.
- Moderate dementia (MMSE score of 20 or less).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| memantineAlso: Namendamemantine 5mg - 20mg PO daily | Drug | memantine |
| Placebo5mg - 20mg PO daily over 8 weeks | Drug | Placebo |
Primary outcome
Montgomery-Asberg Depression Rating Score (MADRS)
Time frame: Baseline & week 8
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.
3 secondary outcomes
Modified Quick Inventory of Depressive Symptoms Self Report Scale (QIDS-SR)
Time frame: baseline & week 8
Hamilton Anxiety Rating Scale (HARS)
Time frame: baseline & week 8
Montgomery-Asberg Depression Rating Score (MADRS)
Time frame: baseline and week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10686270Berman 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.
- Background: PubMed 8361950Moryl 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.
- Background: PubMed 12934985Oquendo 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.
- Background: PubMed 7821340Papp 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.
- Background: PubMed 15156068Rogoz 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.
- Background: PubMed 8852530Skolnick 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.
- Derived from this study: PubMed 34510411Dean 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.
- Derived from this study: PubMed 24229746Smith 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.
- Center for Psychopharmacologic Research and TreatmentLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristina M Deligiannidis, M.D. principal investigator
University of Massachusetts, Worcester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing memantine in people with Depressive Disorder, run by University of Massachusetts, Worcester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Score (MADRS) (time frame: Baseline & week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00344682, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2018.