Combination of Dextromethorphan and Memantine in Treating Bipolar Disorder

Study Overview
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Brief Summary
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This is a research clinical trial of double-blind, stratified randomized, parallel group, two-centre study. It will be conducted in a total of 250 300 male and female subjects from the Department of Psychiatry at National Cheng Kung University Hospital. Eligible subjects will be psychiatric out- and in-patients, aged between 18 65 years old, who have psychiatric evaluation with clinically suspected of having bipolar II disorder and fulfill the inclusion and exclusion criteria. The add-on double-blind study treatment with dextromethorphan/place will commence at randomization for while patients continue open-label valproate. Subjects will be enrolled for 12 weeks double-blind add-on treatment and randomly assigned to (1) 30mg dextromethorphan+valproate, (2) 5mg memantine+valproate, (3) dextromethorphan+memantine+valproate or (4) placebo+valproate. Concomitant benzodiazepine medication (preferably up to 8mg lorazepam) may be used for daytime sedation, agitation or insomnia during the study. For the consideration of the less influence to immune-system, resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be chose. We will measure the treatment response and side effect to clarify the curative effect of DM and memantine add-on therapy to valproate in the treatment of bipolar disorders. This study is being performed to investigate the possibly significant beneficial effects on the subtypes of bipolar disorders psychopathology.

Detailed Description
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A total of 250 300 male and female subjects from the Department of Psychiatry at National Cheng Kung University Hospital. Eligible subjects who are aged between 18 65 years old and clinically suspected of having bipolar II disorder are invited. The add-on double-blind study treatment with dextromethorphan/place will commence at randomization for while patients continue open-label valproate. Subjects will be enrolled for 12 weeks double-blind add-on treatment and randomly assigned to (1) 30mg dextromethorphan+valproate, (2) 5mg memantine+valproate, (3) dextromethorphan+memantine+valproate or (4) placebo+valproate. Concomitant benzodiazepine medication (preferably up to 8mg lorazepam) may be used for daytime sedation, agitation or insomnia during the study. For the consideration of the less influence to immune-system, resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be chose. We will measure the treatment response and side effect to clarify the curative effect of DM and memantine add-on therapy to valproate in the treatment of bipolar disorders. This study is being performed to investigate the possibly significant beneficial effects on the subtypes of bipolar disorders psychopathology.

Official Title
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Combination of Dextromethorphan and Memantine in Treating Bipolar Disorder

Conditions
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Bipolar Disorder II

Intervention / Treatment
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* Drug: Dextromethorphan
* Drug: Memantine
* Drug: dextromethorphan+memantine
* Drug: placebo+valproate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A 2-day minimum for hypomania to diagnose bipolar II disorder A total of Hamilton Rating Scale for Depression scored at least 18 or Young Mania Rating Scale scored at least 14 at the screening stage Must allow to ensure acceptable compliance and visit Exclusion Criteria: Pregnant females or nursing Women of childbearing potential not using adequate contraception Received dextromethorphan, memantine, other antiinflammatory medication within 1 week prior Clinically significant medical condition (cardiac, hepatic and renal disease) Received electroconvulsive therapy patients within 4 weeks prior to the first dose of double-blind medication Increase in total SGOT, SGPT, BUN and creatinine by more than 3X upper limit of normal.

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 |
| --- | --- |
| Experimental: 30 mg DM<br>30mg dextromethorphan+valproate | Drug: Dextromethorphan<br> <br> * Other names: 30mg dextromethorphan;|
| Experimental: 5 mg MM<br>5mg memantine+valproate | Drug: Memantine<br> <br> * Other names: 5mg memantine+valproate;|
| Experimental: DM+MM<br>dextromethorphan+memantine+ valproate | Drug: dextromethorphan+memantine<br> <br> |
| Placebo Comparator: placebo<br>Placebo+valproate | Drug: placebo+valproate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment change assessed by plasma levels of cytokines (e.g., IL-6, IL-8) | change assessment | baseline, week 1, week 2, week 4, week 8, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| depression change change | depression change assessed by Hamilton Depression Rating Scale | baseline, week 1, week 2, week 4, week 8, week 12 | 
| manic state change | Manic symptom assessed by Young Mania Rating Scale | baseline, week 1, week 2, week 4, week 8, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dextromethorphan; memantine; treatment response