Bipolar Disorder, Depression
Conditions
Keywords
Lamotrigine, Divalproex, Antidepressant
Brief summary
This study will compare two different antidepressant treatment regimens to determine which is more effective in reducing symptoms of bipolar depression.
Detailed description
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.
Interventions
DRUGLamotrigine
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.
DRUGDivalproex (DIV) ER
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.
DRUGPlacebo
During the randomized phase participants randomized to placebo comparator group will discontinue DIV and will start taking the placebo in the same fashion.
Sponsors
National Institute of Mental Health (NIMH)
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mania Rating Scale | up to 8 months | 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. |
Participant flow
Recruitment details
Recruitment from October 2004 to September 2007 took place in Univ of Texas Health Science Center San Antonio and Center for Healthcare services and television advertisements.
Pre-assignment details
1st 8 weeks is Open Label phase. Subjects are either in a depressed episode or have been depressed in last 6 mos. In this phase subjects will take lamotrigine and divalproex ER. Those who remained depressed, or developed an episode, during 2 consecutive visits, were terminated at, or by, week 8.
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine Plus Divalproex ER Enrolled subjects received lamotrigine and divalproex ER | 41 |
| Lamotrigine Plus Placebo Divalproex ER | 45 |
| Total | 86 |
Baseline characteristics
| Characteristic | Lamotrigine Plus Placebo Divalproex ER | Lamotrigine Plus Divalproex ER | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 41 Participants | 86 Participants |
| Age, Continuous | 42.1 years STANDARD_DEVIATION 12.7 | 37.6 years STANDARD_DEVIATION 11 | 39.9 years STANDARD_DEVIATION 11.9 |
| Region of Enrollment United States | 45 participants | 41 participants | 86 participants |
| Sex: Female, Male Female | 26 Participants | 21 Participants | 47 Participants |
| Sex: Female, Male Male | 19 Participants | 20 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 41 | 0 / 45 |
| serious Total, serious adverse events | 0 / 41 | 0 / 45 |
Outcome results
Primary
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.
Time frame: up to 8 months
Population: all randomized subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Lamotrigine and Divalproex ER | Mania Rating Scale | 4.54 units on a scale | Standard Error 0.64 |
| Double-Blind Lamotrigine and Placebo Divalproex ER | Mania Rating Scale | 5.57 units on a scale | Standard Error 0.6 |