Memantine Augmentation of Antidepressants

NCT00344682 | Completed Phase 4 Results

• 1 other identifier: NAM-MD-34
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Depressive Disorder

Keywords

memantine; Namenda; augmentation; add-on; depression; MDD (major depressive disorder); unipolar depression; NMDA; ketamine; uncompetitive NMDA receptor antagonist

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Modified Quick Inventory of Depressive Symptoms Self Report Scale (QIDS-SR)

  baseline & week 8

• Hamilton Anxiety Rating Scale (HARS)

  baseline & week 8

• Montgomery-Asberg Depression Rating Score (MADRS)

  baseline and week 8

Study Arms (2)

memantine

EXPERIMENTAL

memantine (5-20mg a day)

Drug: memantine

Placebo

PLACEBO COMPARATOR

placebo (5-20mg a day)

Drug: Placebo

Interventions

memantine DRUG

memantine 5mg - 20mg PO daily

Also known as: Namenda

memantine

Placebo DRUG

5mg - 20mg PO daily over 8 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• mg qD of fluoxetine (Once Daily)
• mg qD of sertraline
• mg qD of paroxetine
• mg qD of fluvoxamine
• mg qD of citalopram
• mg qD of escitalopram
• mg qD of venlafaxine or venlafaxine sustained release
• mg qD of bupropion or bupropion sustained or extended release
• mg qD of mirtazapine
• mg qD of duloxetine

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead
• Forest Laboratories: collaborator

Study Sites (1)

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

Worcester, Massachusetts, 01605, United States

Location

Related Publications (8)

• 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.

  PMID: 10686270 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.

  PMID: 8361950 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.

  PMID: 12934985 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.

  PMID: 7821340 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.

  PMID: 15156068 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.

  PMID: 8852530 BACKGROUND

• 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.

  PMID: 34510411 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.

  PMID: 24229746 DERIVED

Related Links

• Center for Psychopharmacologic Research and Treatment

MeSH Terms

Conditions

Depressive Disorder; Depression; Depressive Disorder, Major

Interventions

Memantine

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Early termination due to slow enrollment, leading to small numbers of subjects enrolled.

Results Point of Contact

• Title: Dr. Kristina Deligiannidis
• Organization: UMass Medical School

kristina.deligiannidis@umassmemorial.org

508-856-5928

Study Officials

• Kristina M Deligiannidis, M.D.

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2006
• First Posted: June 27, 2006
• Study Start: June 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: July 11, 2018
• Results First Posted: November 25, 2013

Record last verified: 2018-06

Locations

US (1)