Memantine Augmentation of Antidepressants

Depressive Disorder Clinical Trial

Official title:

A Randomized Double-Blind Pilot Study of Memantine Augmentation in Antidepressant Nonresponders or Incomplete Responders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00344682
• Other study ID #: NAM-MD-34
• Status: Completed
• Phase: Phase 4
• Start date: June 2006
• Est. completion date: December 2011

Study information

• Verified date: June 2018
• Source: University of Massachusetts, Worcester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Drug:
• memantine
memantine 5mg - 20mg PO daily
• Placebo
5mg - 20mg PO daily over 8 weeks

Locations

Country	Name	City	State
United States	Center for Psychopharmacologic Research and Treatment (University of Massachusetts Medical School)	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
University of Massachusetts, Worcester	Forest Laboratories

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

Moryl E, Danysz W, Quack G. Potential antidepressive properties of amantadine, memantine and bifemelane. Pharmacol Toxicol. 1993 Jun;72(6):394-7. — View Citation

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. — View Citation

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. — View Citation

Rogóz Z, Skuza G, Kusmider M, Wójcikowski 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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline & week 8
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.	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.	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.	baseline and week 8

External Links

•   Center for Psychopharmacologic Research and Treatment