Memantine Augmentation of Lamotrigine Incomplete-Response in Bipolar Depression

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether addition of memantine to bipolar depression patients who have had an incomplete response to lamotrigine (Lamictal) which is frequently used to treat bipolar depression in the clinical setting. At present, memantine is approved for use in the treatment of Alzheimer's disease or dementia, but not for use for the treatment of bipolar depression. Subjects will be asked to participate because they are suffering from bipolar depression associated and have had an inadequate response to lamotrigine. Subjects will have to be on at least 100 mg per day, for at least 4 weeks.

Detailed Description
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Hypothesis/Objectives: H1: Lamotrigine inadequate-response patients augmented with memantine for 8 weeks will have significantly greater improvement on the Hamilton Depression Rating Scale (HDRS) and Clinical Global Improvement (CGI) scale compared to patients augmented with placebo. H2: Lamotrigine inadequate-response patients augmented with memantine for 8 weeks will have significantly greater improvement of scores on the Selective Reminding Test (SRT), the Digit Span Test, the Stroop Test, and Trail Making Test (TMT) than patients augmented with placebo. Study Population: We will study 40 bipolar disorder depressed (BDD) outpatients (20 in each arm) recruited from the outpatient Mood Disorders Clinic and by advertisement.

Official Title
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Memantine Augmentation of Lamotrigine Incomplete Response in Bipolar Depression: A Randomized Placebo Controlled Clinical Trial

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: Memantine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:: 1) age 18 - 65; 2) satisfy DSM-IV-TR criteria for Bipolar Disorder and Major Depressive Episode; 3) Lamotrigine Inadequate-Response: Defined as already treated with at least 100 mg of lamotrigine for at least 4 weeks but 17 item HDRS rating > 15; 4) give informed consent as approved by local IRB; 5) if on other antidepressants or mood stabilizers on stable dose for the past 4 weeks. Exclusion Criteria:1) comorbid psychotic disorder such as schizophrenia or schizoaffective disorder; 2) significant suicidal or homicidal risk; 3) clinically significant medical illness; 4) allergy or intolerance to lamotrigine or memantine; 5) pregnancy, planning to be pregnant or not using adequate contraception; 6) satisfy criteria for substance dependence within 6 months prior to start of the study; and 7) on any medication with significant adverse interaction with either lamotrigine or memantine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo daily | Drug: Placebo<br>* No active medication, only placebo<br>|
| Active Comparator: Memantine<br>Daily dose Memantine | Drug: Memantine<br>* Memantine will be given orally. Subjects will be started at a dose of 5 mg for the first week and then increased by 5 mg every week up to a maximum of 20 mg depending on response and tolerance and will be kept at that level for the rest of the study. This is an 8 week study.<br>* Other names: Memantine or Namenda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 17-item Hamilton Depression Rating Scale From Baseline to 8 Weeks (Baseline - 8 Wks) | Scale for measurement of depression severity. Total of scale is used. Total range is from 0 - 50 with higher score signifying higher severity of depression. Outcome measure is change in score from baseline to 8 wks. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar, Depression, Incomplete Response