Depression, Bipolar
Conditions
Brief summary
The purpose of this study is to examine the safety and efficacy of Depakote ER in bipolar depression and to evaluate metabolic and GABA changes with Depakote ER administration using PET and MRI/MRS brain imaging techniques.
Detailed description
Mood disorders are important public health problems. Bipolar disorder is a major psychiatric disorder characterized by mood cycles alternating between mania and depression and affects approximately 1% of the population. Most patients are treated beginning in the early twenties and then embark on a course marked by multiple recurrences, hospitalizations, and encounters with legal authorities. These disorders inflict substantial morbidity which yields important deficits in occupational and interpersonal function. The risk of suicide in mood disorders may be as high as 10%. Although the outlook for recovery from acute manic or depressive episodes is generally excellent, the long-term prognosis of the disorder varies tremendously across the patient population. The introduction of lithium, anticonvulsants and atypical antipsychotics significantly changes the outlook for bipolar disorder, with some individuals on chronic treatment attaining complete remission and indefinite prophylaxis against mood episodes. However, such optimum outcomes may be limited to as few as one-third to one-half of all treated patients. The remaining experiences various combinations of breakthrough mood episodes, including chronic mood instability, persistent depression, and rapid cycling. Very little research has been conducted with bipolar disorder, and no medications have an FDA indication to treat bipolar depression. Previous studies suggest that Depakote is promising in the treatment of mixed and depressed episodes of bipolar disorder. This study utilizes the extended release formulation of divalproex sodium, with demonstrated increased tolerability. We propose investigating safety, tolerability and efficacy of Depakote ER monotherapy in Bipolar I, II or NOS depression, and monitoring associated changes in brain GABA levels. In addition, we intend to evaluate and assess the differences between brain metabolic rate and GABA levels in bipolar disorder patients and healthy volunteers.
Interventions
DRUGDepakote ER
Depakote ER
Sponsors
Abbott
National Alliance for Research on Schizophrenia and Depression
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Bipolar I, II or NOS currently suffering from depression * Both: both female and male participants are being studied * Adults 18 years and older of any race
Exclusion criteria
* Schizophrenia or schizoaffective disorder and other disorders excluded at the discretion of the investigator's discretion * Substance dependence within the past 3 months and abuse within the past 2 weeks prior to study. * Positive screen for psychoactive drugs, stimulants or drugs of abuse (excluding marijuana, as long as dependence and abuse are ruled out according to DSM-IV) * Significant risk harm to self or others based on history and mental status exam * Clinically significant or unstable medical condition * Unstable thyroid pathology and treatment initiated or altered within the past 3 months * Clinically significant abnormal laboratory test results, vital signs, as judged by the investigators * Women pregnant or nursing, or WOCBP who do not use adequate contraception or who are judged to be unreliable in their use of contraception * Subjects who failed (because of inefficacy or adverse effects) an adequate trial of Depakote; eligible patient's may not have received Depakote within 30 days of screen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery Asberg Depression Rating Scale (MADRS) | Baseline, 7 weeks | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression the overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response to the Divalproex-ER in Acute Bipolar 2 Depression. | 7 weeks | A reduction greater than or equal to 50% in MADRS total score from baseline to the endpoint. |
Countries
United States
Participant flow
Recruitment details
Eligible patients were recruited from the Bipolar Disorders Clinic at the Stanford University School of Medicine in Stanford, California. Patients met DSM-IV criteria for bipolar II disorder, with a current major depressive episode, as determined by the Systematic Treatment Enhancement for Bipolar Disorder (STEP-BD)
Participants by arm
| Arm | Count |
|---|---|
| Depakote ER Depakote ER up to 1500 mg/day
Depakote ER: Depakote ER | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Not reported as to reason | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Depakote ER |
|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 9.1 |
| Montgomery Asberg Depression Rating Scale (MADRS) Total Score | 30.1 units on a scale STANDARD_DEVIATION 4.5 |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Montgomery Asberg Depression Rating Scale (MADRS)
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression the overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression.
Time frame: Baseline, 7 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Depakote ER | Montgomery Asberg Depression Rating Scale (MADRS) | 14.9 units on a scale | Standard Deviation 9.8 |
p-value: <0.00001Wilcoxon (Mann-Whitney)
Secondary
Response to the Divalproex-ER in Acute Bipolar 2 Depression.
A reduction greater than or equal to 50% in MADRS total score from baseline to the endpoint.
Time frame: 7 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Depakote ER | Response to the Divalproex-ER in Acute Bipolar 2 Depression. | 11 participants |