Memantine Augmentation of Antidepressants

NCT ID: NCT00344682

Last Updated: 2018-07-11

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-06-30

Study Completion Date

2011-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

\- 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

See the medical conditions and disease areas that this research is targeting or investigating.

Depressive Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

memantine

memantine (5-20mg a day)

Group Type EXPERIMENTAL

memantine

Intervention Type DRUG

memantine 5mg - 20mg PO daily

Placebo

placebo (5-20mg a day)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

5mg - 20mg PO daily over 8 weeks

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

memantine

memantine 5mg - 20mg PO daily

Intervention Type DRUG

Placebo

5mg - 20mg PO daily over 8 weeks

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Namenda

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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:

* 20 mg qD of fluoxetine (Once Daily)
* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Forest Laboratories

INDUSTRY

Sponsor Role collaborator

University of Massachusetts, Worcester

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Kristina M Deligiannidis, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Massachusetts, Worcester

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Center for Psychopharmacologic Research and Treatment (University of Massachusetts Medical School)

Worcester, Massachusetts, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 10686270 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8361950 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12934985 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7821340 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15156068 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8852530 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34510411 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24229746 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.umassmed.edu/psychopharm

Center for Psychopharmacologic Research and Treatment

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NAM-MD-34

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Pattern Separation in Major Depressive Disorder
NCT07139834 NOT_YET_RECRUITING PHASE1
Org 24448 to Treat Major Depression
NCT00113022 TERMINATED PHASE2