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

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2008

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.

Intervention(s) in this Clinical Trial

• Drug: Lamotrigine (LAM)
  • 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.
• Drug: Divalproex (DIV)
  • 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.
• Drug: Placebo
  • During the randomized phase participants randomized to placebo comparator group will discontinue DIV and will start taking the placebo in the same fasion.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Participants will take active lamotrigine and active divalproex
• Placebo Comparator: 2
  • Participants will take active lamotrigine and placebo

Primary Measures

• Rates of response to treatment regimen
  • Time Frame: Measured at Week 32
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Charles L. Bowden, MD Principal Investigator 210-567-5405  

Overall Contact: Martha L. Dahl, RN 210-567-5501 dahlml@uthscsa.edu

Information obtained from ClinicalTrials.gov on December 03, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00183469

Study ID Number: P20 MH68662

ClinicalTrials.gov Identifier: NCT00183469

Health Authority: United States: Food and Drug Administration