Series Studies of Bipolar Disorder-Valproate add-on Memantine

Study Overview
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Brief Summary
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All participants should fulfill the following criteria: aged between 18 and 65 years old, and of domestic Han descendants. Participants will be randomly assigned to either the (1) pharmacotherapy (valproate add-on memantine) group; (2) pharmacotherapy (valproate add-on memantine) plus Cognitive Behavior Group Therapy (CBGT) group; (3) valproate add-on placebo plus CBGT group, or (4) valproate add-on placebo only group. A total of 240-320 individuals (60-80 participants per group) will be recruited for this study. For each CBGT group, 12-weekly sessions are scheduled according to patients' preference. The investigators will attempt to understand the effects of pharmaceutical drugs for mood stabilizers add-on neuro-protective drugs, pharmacotherapy with CBGT, mood stabilizer with CBGT, and the use of only traditional mood stabilizers in the treatment of BP II. Comparisons will be made for each type of treatment and possible mechanisms will be examined regarding the pharmacotherapy and CBGT for bipolar disorder patients.

Official Title
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Series Studies of Bipolar Disorder-Valproate add-on Memantine Treatment

Conditions
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Bipolar Disorders

Intervention / Treatment
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* Drug: Memantine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient aged >=18 and <= 65 years. A diagnosis of bipolar II disorder according to DSM-IV-TR criteria made by a specialist in psychiatry. A total of HDRS score at least 18 or YMRS score at least 14 at screen. Signed informed consent by patient or legal representative. Exclusion Criteria: Women of childbearing potential not using adequate contraception as per investigator judgment or not willing to comply with contraception for duration of study. Females who are pregnant or nursing. Patient has received memantine or other selective cyclo-oxygenase 2 (Cox-2) inhibitors within 1 week prior to first dose of double-blind medication. Axis-I DSM-IV-TR diagnosis other than bipolar II disorder. Current evidence of an uncontrolled and/or clinically significant medical condition (e.g., cardiac, hepatic and renal failure), which in the judgments of the investigator, would compromise patient safety or preclude study participation. History of intolerance to valproate or memantine or other Cox-2 inhibitors. History of sensitivity reaction (e.g., urticaria, angioedema, bronchospasm, severe rhinitis, anaphylactic shock) precipitated by memantine Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to first dose of doubleblind medication. Inclusion in another bipolar disorder study or study for another indication with psychotropic's within the last 30 days prior to start of study. Increase in total SGOT, SGPT, BUN and creatinine by more than 3X ULN (upper limit of normal). Substance-related disorders within 6 months prior to study start, borderline personality disorder, schizophrenia, or other major psychiatric disorders as defined by DSM-IV criteria.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VPA & Placebo<br>VPA & Placebo | Drug: Placebo<br> <br> |
| Experimental: VPA & memantine<br> | Drug: Memantine<br>* 5 mg per day of memantine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Young's Mania Rating Scale (YMRS) | Normally, YMRS is used to evaluate the Bipolar Disorder Patient's mood change. | baseline, 1, 2, 4, 8 and 12 weeks | 
| Hamilton Depression Rating Scale (HDRS) | Normally, YMRS is used to evaluate the Bipolar Disorder Patient's mood change of depression. | baseline, 1, 2, 4, 8 and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cytokines |  | baseline, 1, 2, 4, 8 and 12 weeks | 
| Clinical Global Impression (CGI) | CGI will be used to evaluate how the patient's adverse effect go on during the trial. | baseline, 1, 2, 4, 8 and the week 12 | 
| lipid profiles | HDL, LDL, cholesterol and etc. | baseline, 1, 2, 4, 8 and 12 weeks |