Double-blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression

Study Overview
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Brief Summary
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Double-Blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression Previously Diagnosed and Treated as Recurrent Major Depression: This study recruits males and females aged 18 - 70 who currently meet diagnostic criteria for bipolar I or bipolar II disorder and are currently experiencing an episode of major depression. Patients are randomized to double-blind treatment with divalproex sodium ER or placebo and remain in the study for up to six weeks. This six-week double-blind treatment period is followed by an open-label treatment period of six months duration. This study is sponsored by Abbott Laboratories.

Official Title
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Double-blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Divalproex Sodium ER
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must give consent to participate in the study and sign and date the IRB approved written informed consent form prior to the initiation of any study procedures Subject must be between the ages of 18 and 70 Subject must have a diagnosis of bipolar I or II. Subject must be currently depressed as confirmed by the Mini-International Neuropsychiatric Interview (MINI) Subject must have a baseline Montgomery-Asberg Depression Scale (MADRS) score of >19 and Young Mania Rating Scale (YMRS) score of <12 Women of childbearing potential must be nonpregnant/nonlactating and using adequate contraception if sexually active Subject must not be using any concomitant psychotropic medications during the acute phase except prn benzodiazepines Exclusion Criteria: Subjects lacks the capacity to provide informed consent Subject has currently or previously used divalproex or Dvpx-ER Subject is a serious suicide risk or has medically unstable conditions as judged by the investigators Subject has any alcohol, cocaine, or cannabis dependence within 3 months of study entry Subject has any cocaine, hallucinogens, opiates, crystal methamphetamine, or MMDA abuse within 3 months of study entry

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Divalproex Sodium ER<br> | Drug: Divalproex Sodium ER<br>* Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.<br>* Other names: Depakote ER;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* . Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | MADRS total scores range from 0-60, where higher scores are indicative of more depression. | Acute phase (week0-week6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Young Mania Rating Scale (YMRS) Total Score | YMRS Scores range from 0 to 60 where higher scores are indicative of more mania. | Acute phase (week0-week6) | 
| Change in General Behavior Inventory (GBI) Depression Scale Score | GBI Depression Scale Scores range from 46-184, where higher scores are indicative of more depression. | Acute phase (week0-week6) | 
| Change in General Behavior Inventory (GBI) Hypomanic/Biphasic Scale Score | GBI Hypomanic/Biphasic Scale scores range from 28-112, where higher scores are indicative of more hypomanic/manic symptoms. | Acute phase (week0-week6) | 
| Change in Short Form Health Survey (SF-36) Physical Component Summary Score | SF-36 Physical Component Summary scores range from 0-100, with a higher score indicating better physical health. | Acute phase (week0-week6) | 
| Change in Short Form Health Survey (SF-36) Mental Component Summary Score | SF-36 Mental Component Summary scores range from 0-100, with a higher score indicating better mental health. | Acute phase (week0-week6) | 
| Change in Hamilton Anxiety Rating Scale (HAMA) Total Score | HAMA Scores range from 0 to 56 where higher scores are indicative of more anxiety. | Acute phase (week0-week6) |