Memantine Augmentation of Antidepressants

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Kristina Deligiannidis, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT00344682
First received: June 22, 2006
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Depressive Disorder
Drug: memantine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind Pilot Study of Memantine Augmentation in Antidepressant Nonresponders or Incomplete Responders

Resource links provided by NLM:


Further study details as provided by University of Massachusetts, Worcester:

Primary Outcome Measures:
  • Montgomery-Asberg Depression Rating Score (MADRS) [ Time Frame: Baseline & week 8 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Modified Quick Inventory of Depressive Symptoms Self Report Scale (QIDS-SR) [ Time Frame: baseline & week 8 ] [ Designated as safety issue: Yes ]
    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.

  • Hamilton Anxiety Rating Scale (HARS) [ Time Frame: baseline & week 8 ] [ Designated as safety issue: No ]
    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.

  • Montgomery-Asberg Depression Rating Score (MADRS) [ Time Frame: baseline and week 8 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 31
Study Start Date: June 2006
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: memantine
memantine (5-20mg a day)
Drug: memantine
memantine 5mg - 20mg PO daily
Other Name: Namenda
Placebo Comparator: Placebo
placebo (5-20mg a day)
Drug: Placebo
5mg - 20mg PO daily over 8 weeks
Other Name: placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00344682

Locations
United States, Massachusetts
Center for Psychopharmacologic Research and Treatment (University of Massachusetts Medical School)
Worcester, Massachusetts, United States, 01605
Sponsors and Collaborators
University of Massachusetts, Worcester
Forest Laboratories
Investigators
Principal Investigator: Kristina M Deligiannidis, M.D. University of Massachusetts, Worcester
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kristina Deligiannidis, Study Principle Investigator, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT00344682     History of Changes
Other Study ID Numbers: NAM-MD-34
Study First Received: June 22, 2006
Results First Received: January 16, 2013
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Massachusetts, Worcester:
memantine
Namenda
augmentation
add-on
depression
MDD (major depressive disorder)
unipolar depression
NMDA
ketamine
uncompetitive NMDA receptor antagonist

Additional relevant MeSH terms:
Depressive Disorder
Depression
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Memantine
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on September 30, 2014