Bipolar Depression, Bipolar Disorder, Depression
Conditions
Keywords
Bipolar Disorder, Major Depression, Clinical pharmacology, Clinical Trial
Brief summary
Mixed states in bipolar disorder have long been recognized. Over a century ago, it was argued that mixed states were the most common episodes in manic-depressive illness. A mixed state is defined as a person who is experiencing symptoms of both depression and mania. Currently, a person must have depression plus 3 or more manic symptoms for the episode to be diagnosed mixed. Using this narrow view, less than 10% of episodes in patients with bipolar disorder would meet criteria for a mixed episode. A broader view requires that the person have at least 2 manic symptoms. Using this broader view, data suggest that about 50% of episodes in bipolar disorder would be diagnosable as mixed states. Studies suggest that the majority of persons with a depressive mixed state have bipolar disorder type II. Many people who have a mixed state will also have major depression. Even with such high potential rates of mixed episodes in both bipolar disorder and major depression, there have been few studies addressing the issue. The purpose of this study is to look at how effective Geodon is in treating the depressive mixed state in people with bipolar or major depression. This will be the first clinical trial that is both double-blind and randomized.
Detailed description
We plan on enrolling 25 subjects from each of the four sites. After signing a consent form, subjects will be screened and asked to have a physical and specific safety labs done to make sure they can safely participate in the study. After the screening visit, subjects will be randomly, like a flip of a coin, placed into one of two groups. One group will get the study drug, Geodon. The other group will get placebo, a sugar pill. Neither the doctor nor subject will know in which group the subject has been placed. Subjects will see the doctor once a week for 6 weeks. During each visit, we will check and treat any side effects. We will ask questions about mood and go through a number of rating scales and assessments that will look at mood and symptoms. Subjects will also fill out questionnaires at each visit to assess their moods and see how the study is going. At the final visit, subjects will have the same physical exam and lab tests done as in the initial visit.
Interventions
ziprasidone, geodon. Dosing instructions began at 40 mg/day and were increased by increments of 20-40 mg weekly weekly based on target symptoms and tolerability with a target range of 80-160 mg/d of ziprasidone for 6 weeks.
DRUGplacebo
Placebo, sugar pill arm. Dosing instructions began at 40 mg/day and were increased by increments of 20-40 mg weekly weekly based on target symptoms and tolerability with a target range of 80-160 mg/d of ziprasidone for 6 weeks.
Sponsors
Pfizer
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of bipolar disorder type II, or unipolar major depressive disorder * If female, non-pregnant/non-lactating * If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation) * Currently meets Diagnostic and Statistical Manual, 4th edition (DSM-IV) criteria for a major depressive episode, and presence of 2 or 3 DSM-IV manic criteria, present for the majority of the time during the past week. * All other baseline psychotropic drugs will be allowed to be continued unchanged. However, if antidepressant use has been initiated in the previous 2 months, or was thought to be contributing to the depressive mixed state, then antidepressant medications would be discontinued 4 weeks before starting the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure Was Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores Over Weeks Between Groups. | Baseline to 6 weeks | Change in Montgomery-Asberg Depression Rating Scale score was compared between placebo and ziprasidone arms. The MADRS measures severity of depressive symptoms. The MADRS scale is from 0 (min) to 40 (max) with 0 being not depressed at all and 40 being the most severely depressed. 0 is the best outcome and 40 is the worst outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Arm Participants in this arm received placebo and were instructed to take it daily for 6 weeks. Participants did not know whether they were taking placebo or ziprasidone (Geodon). | 38 |
| Geodon Arm Participants in this arm received Geodon and were instructed to take it daily for 6 weeks. Participants did not know whether they were taking placebo or ziprasidone (Geodon). | 35 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo Arm | Geodon Arm |
|---|---|---|---|
| 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 | 73 Participants | 38 Participants | 35 Participants |
| Age, Continuous | 38.7 years STANDARD_DEVIATION 12.2 | 38.6 years STANDARD_DEVIATION 12.7 | 39.1 years STANDARD_DEVIATION 11.9 |
| Region of Enrollment United States | 73 participants | 38 participants | 35 participants |
| Sex: Female, Male Female | 38 Participants | 20 Participants | 18 Participants |
| Sex: Female, Male Male | 35 Participants | 18 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 38 | 3 / 35 |
| serious Total, serious adverse events | 0 / 38 | 0 / 35 |
Outcome results
Primary
The Primary Outcome Measure Was Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores Over Weeks Between Groups.
Change in Montgomery-Asberg Depression Rating Scale score was compared between placebo and ziprasidone arms. The MADRS measures severity of depressive symptoms. The MADRS scale is from 0 (min) to 40 (max) with 0 being not depressed at all and 40 being the most severely depressed. 0 is the best outcome and 40 is the worst outcome.
Time frame: Baseline to 6 weeks
Population: Power analysis, with beta=0.20 and two-tailed alpha=0.05, was based on pilot studies for the mania registration trials which included mixed episodes and assessed MADRS scores. A projected standard error of the mean difference was assumed to be about twice as much as the mean difference (5-15 points), producing a sample size of about 100.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ziprasidone Arm | The Primary Outcome Measure Was Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores Over Weeks Between Groups. | 11.4 Scores on a scale |
| Placebo Arm | The Primary Outcome Measure Was Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores Over Weeks Between Groups. | 5.9 Scores on a scale |
95% CI: [0.6, 10.2]