Maintenance Treatment of Bipolar Depression

Study Overview
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Brief Summary
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This study will compare two different antidepressant treatment regimens to determine which is more effective in reducing symptoms of bipolar depression.

Detailed Description
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Depression is a serious condition that is often difficult to diagnosis and treat. Bipolar disorder-related depression is especially complex because of the presence of mania symptoms. Lamotrigine and divalproex are commonly prescribed medications for depression. However, their effectiveness in treating bipolar depression has not been thoroughly evaluated. Studies have shown that combining lamotrigine with another antidepressant may be more effective in reducing depressive symptoms than lamotrigine alone. This study will provide participants with either lamotrigine alone or in combination with divalproex and will determine which regimen is more effective in reducing symptoms of bipolar depression. Participants will be randomly assigned to a daily regimen of either lamotrigine and divalproex or lamotrigine and placebo for 8 months. Participants will be assessed at study entry, at two unspecified times during the study, and at the end of the study. During each assessment, participants will undergo a brief interview and complete a questionnaire about their depressive symptoms, any physical manifestations of their depression, and their overall level of functioning in daily activities.

Official Title
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Eight-Month Maintenance Treatment of Bipolar Depression With Lamotrigine or Lamotrigine Plus Divalproex Combination

Conditions
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Bipolar Disorder, Depression

Intervention / Treatment
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* Drug: Lamotrigine
* Drug: Divalproex (DIV) ER
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of bipolar disorder I or II Experiencing symptoms of depression at study entry OR have experienced symptoms of depression within 6 months prior to study entry Willing to use acceptable methods of contraception Parent or guardian willing to provide informed consent, if applicable Exclusion Criteria: History of liver disease History of substance abuse Previous treatment with lamotrigine or divalproex Lamotrigine or divalproex intolerance

Ages Eligible for Study
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Minimum Age: 18 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: lamotrigine plus divalproex ER<br>Participants will take active lamotrigine and active divalproex ER | Drug: Lamotrigine<br>* If the participant is naive to LAM, LAM will be started at 25 mg every day for the first 2 weeks, then 50 mg per day for the next 2 weeks. The dose of LAM can be increased to 100 mg at week 5 and increased to maximum of 200 mg at week 6 based on symptoms, tolerability, and ratings of the rating scales. If the participant is already taking LAM, the dose will be increased to up to 200 mg using the same guide lines. Upon randomization the participant in the placebo comparator will have their dosage titrated to doubled since the potentiating effect of the Divalproex will no longer exist. It will remain at this dosage until the end of the study with the possibility of one adjustment for side effects.<br>* Other names: (LAM);Drug: Divalproex (DIV) ER<br>* If the participant is naive to DIV and if LAM was initiated before the start of treatment with DIV, DIV can be started at any point of time in the study provided the participant has been on LAM for at least 2 weeks. DIV will be started at 500 mg and titrated by increments of 500 mg every 3 to 4 days until a therapeutic blood level is attained up to 2500 mg.<br>* Other names: valproic Acid;|
| Placebo Comparator: lamotrigine plus placebo divalproex ER<br>Participants will take active lamotrigine and placebo | Drug: Lamotrigine<br>* If the participant is naive to LAM, LAM will be started at 25 mg every day for the first 2 weeks, then 50 mg per day for the next 2 weeks. The dose of LAM can be increased to 100 mg at week 5 and increased to maximum of 200 mg at week 6 based on symptoms, tolerability, and ratings of the rating scales. If the participant is already taking LAM, the dose will be increased to up to 200 mg using the same guide lines. Upon randomization the participant in the placebo comparator will have their dosage titrated to doubled since the potentiating effect of the Divalproex will no longer exist. It will remain at this dosage until the end of the study with the possibility of one adjustment for side effects.<br>* Other names: (LAM);Drug: Placebo<br>* During the randomized phase participants randomized to placebo comparator group will discontinue DIV and will start taking the placebo in the same fashion.<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mania Rating Scale | Severity of the illness and psychopathological features will be measured by the increase in the SADS Mania Rating Scale, with higher scores representing worse mania. The range of this scale is 0-75. | up to 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Divalproex, Lamotrigine, Antidepressant