Bipolar Disorder, Depression
Conditions
Keywords
Bipolar Type II Disorder, Hypomania, Antidepressant, Mood Stabilizer, Venlafaxine, Lithium Carbonate, Major Depressive Episode, Hypomanic Episodes, Prevention of Depression Relapse
Brief summary
This study will compare the safety and effectiveness of antidepressant therapy versus mood stabilizing therapy in treating people with bipolar type II major depression.
Detailed description
Bipolar type II (BP II) depression affects 2.5% of the U.S. adult population. People with BP II disorder do not experience the manic episodes that are characteristic of BP I disorder, but rather they experience more modest mood swings with a greater number of major depressive episodes (MDEs). These MDEs are associated with high rates of disease and death. The treatment of BP II depression remains a challenge for clinicians. Mood stabilizer (MS) monotherapy is the current recommended treatment for BD II MDE, but there is reason to believe that antidepressant drug (AD) monotherapy could also be an effective treatment. However, concerns over AD-induced manic switch episodes have limited the use of this treatment option. Preliminary studies using the ADs fluoxetine or venlafaxine have shown success in treating and lowering the manic switch rate of those with BP II MDE. This study will compare the safety and effectiveness of AD monotherapy versus MS monotherapy in treating people with BP II major depression. Participation in this double-blind study will last up to 9 months. After screening, which includes a medical and psychiatric history review, a physical exam, an electrocardiogram (EKG) test, clinical laboratory tests, a urine-based drug test, and a pregnancy test if applicable, participants will be randomly placed into one of two treatment groups. Participants in the AD monotherapy group will be treated with venlafaxine, and participants in the MS monotherapy group will be treated with lithium. During the first 12 weeks, there will be a total of nine study visits lasting between 45 and 60 minutes. In these visits, participants will receive their study drug and will undergo various assessments, including a review of medication history and side effects, vital sign measurements, and questionnaires about depression and daily functioning. Blood samples will be taken at most visits. Participants who respond well during the initial 12 weeks of therapy with either drug will have the option to continue treatment for 6 additional months. During this time, participants will continue their assigned treatment and will attend five monthly study visits that will repeat previous assessments and procedures. For information on a related study, please follow this link: http://clinicaltrials.gov/show/NCT00044616
Interventions
DRUGVenlafaxine
75 to 375 mg
DRUGLithium Carbonate
300 to 2400 mg
Sponsors
National Institute of Mental Health (NIMH)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meets DSM-IV criteria for Axis I bipolar II disorder * Meets DSM-IV criteria for Axis I major depressive episode * Score of 16 on 17-item HAM-D rating scale * Not taking monoamine oxidase inhibitors (MAOI) for more than 2 weeks prior to study entry * Willing to use an effective form of birth control throughout the study
Exclusion criteria
* History of mania * Current primary Axis I diagnosis other than bipolar II disorder * Alcohol or drug dependence within 3 months prior to study entry * Contraindication to treatment with venlafaxine or lithium * Unstable medical condition (e.g., thyroid disease, hypertension, or angina pectoris) * Pregnant or breastfeeding * Experiencing suicidal thoughts * Requires hospitalization * Requires concurrent neuroleptic or MS therapy * Requires concurrent AD therapy * Current psychotic features * Inadequate trial of therapy at the time of initial screening visit * History of intolerance to either venlafaxine or lithium * Unlikely to participate in a 36-week trial * Presence of apparent secondary gain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Relapse | Weeks 16, 20, 24, 30, 36 | These subjects must be responders. Outcome measures were obtained at continuation weeks. Participant would be considered depressive relapse if relapsed by any of these times. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Mood Symptoms | Measured at Weeks 12 and 36 | These subjects must be responders. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Antidepressant Therapy Venlafaxine: 75 to 375 mg | 42 |
| Mood Stabilizer Therapy Lithium Carbonate: 300 to 2400 mg | 17 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12 Week Double Blind Comparison | Adverse Event | 2 | 5 |
| 12 Week Double Blind Comparison | Lack of Efficacy | 13 | 23 |
| 12 Week Double Blind Comparison | Lost to Follow-up | 5 | 6 |
| 12 Week Double Blind Comparison | Withdrawal by Subject | 3 | 13 |
| Follow Up Study Comparison | Adverse Event | 1 | 0 |
| Follow Up Study Comparison | Lost to Follow-up | 8 | 1 |
| Follow Up Study Comparison | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Mood Stabilizer Therapy | Antidepressant Therapy |
|---|---|---|---|
| Age 1st hypomanic episode | 19.4 years STANDARD_DEVIATION 8.5 | 16.2 years STANDARD_DEVIATION 10 | 20.7 years STANDARD_DEVIATION 7.6 |
| Age 1st major depressive episode | 18.5 years STANDARD_DEVIATION 7.1 | 17.4 years STANDARD_DEVIATION 5.4 | 19.0 years STANDARD_DEVIATION 7.7 |
| Age, Continuous | 42.2 years STANDARD_DEVIATION 12.5 | 43.1 years STANDARD_DEVIATION 15.2 | 41.8 years STANDARD_DEVIATION 11.4 |
| Baseline HRSD score | 19.2 units on a scale STANDARD_DEVIATION 3.5 | 18.8 units on a scale STANDARD_DEVIATION 3.3 | 19.4 units on a scale STANDARD_DEVIATION 3.6 |
| Baseline HRSD Score for Follow-Up study | 4.3 units on a scale STANDARD_DEVIATION 2.9 | 4.4 units on a scale STANDARD_DEVIATION 3.4 | 4.3 units on a scale STANDARD_DEVIATION 2.8 |
| Baseline YMRS score | 0.8 units on a scale STANDARD_DEVIATION 1.6 | 0.6 units on a scale STANDARD_DEVIATION 1.4 | 0.8 units on a scale STANDARD_DEVIATION 1.7 |
| Duration major depressive episode | 4 months | 4.0 months | 4.5 months |
| Inter-episode recovery | 16 Participants | 2 Participants | 14 Participants |
| Number of lifetime hypomanic episodes | 41.9 Episodes STANDARD_DEVIATION 61.4 | 32.2 Episodes STANDARD_DEVIATION 47.3 | 45.8 Episodes STANDARD_DEVIATION 66.4 |
| Number of lifetime major depressive episodes | 29.9 Episodes STANDARD_DEVIATION 11 | 33.3 Episodes STANDARD_DEVIATION 49.7 | 28.4 Episodes STANDARD_DEVIATION 50.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 49 Participants | 12 Participants | 37 Participants |
| Sex: Female, Male Female | 32 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Male | 27 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 65 | 0 / 64 |
| serious Total, serious adverse events | 0 / 65 | 0 / 64 |
Outcome results
Primary
Depressive Relapse
These subjects must be responders. Outcome measures were obtained at continuation weeks. Participant would be considered depressive relapse if relapsed by any of these times.
Time frame: Weeks 16, 20, 24, 30, 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Antidepressant Therapy | Depressive Relapse | 3 Participants |
| Mood Stabilizer Therapy | Depressive Relapse | 4 Participants |
Secondary
Treatment-Emergent Mood Symptoms
These subjects must be responders.
Time frame: Measured at Weeks 12 and 36
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Antidepressant Therapy | Treatment-Emergent Mood Symptoms | Any depression | 15 Participants |
| Antidepressant Therapy | Treatment-Emergent Mood Symptoms | Any subsyndromal hypomania | 3 Participants |
| Mood Stabilizer Therapy | Treatment-Emergent Mood Symptoms | Any depression | 11 Participants |
| Mood Stabilizer Therapy | Treatment-Emergent Mood Symptoms | Any subsyndromal hypomania | 3 Participants |