Safety Study of Ziprasidone (Geodon) for the Depressive Mixed State
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo arm Participants were instructed by a physician to take a study drug daily. 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. Participants were not informed whether they were receiving sugar pills or Geodon. Participants in this study arm received sugar pills. |
Drug: placebo
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.
|
| Active Comparator: Geodon arm Participants were instructed by a physician to take a study drug daily. 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. Participants were not informed whether they were receiving sugar pills or Geodon. Participants in this study arm received Geodon. |
Drug: ziprasidone (Geodon)
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.
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Northwestern University | Chicago | Illinois | United States | 60201 |
| 2 | Tufts University | Boston | Massachusetts | United States | 02111 |
| 3 | Cambridge Health Alliance | Cambridge | Massachusetts | United States | 02139 |
| 4 | Duke University | Durham | North Carolina | United States | 27704 |
Sponsors and Collaborators
- Tufts Medical Center
- Pfizer
Investigators
- Principal Investigator: Nassir Ghaemi, MD, MPH, Tufts University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GA128000
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Double-blind Flexible-dose Placebo Arm | Double-blind Flexible-dose Ziprasidone Arm |
|---|---|---|
| Arm/Group Description | 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). Dosing was flexible. Dosing for all subjects was determined based on clinician judgment in an identical manner to dosing in the ziprasidone arm. | Participants in this arm received a flexible dose of ziprasidone and were instructed to take it daily for 6 weeks. Participants did not know whether they were taking placebo or ziprasidone (Geodon). Dosing for all subjects began at 20 mg twice a day and increased to between 80 and 160 mg/day total. |
| Period Title: Overall Study | ||
| STARTED | 38 | 35 |
| COMPLETED | 31 | 31 |
| NOT COMPLETED | 7 | 4 |
Baseline Characteristics
| Arm/Group Title | Placebo Arm | Geodon Arm | Total |
|---|---|---|---|
| Arm/Group Description | 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). | 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). | Total of all reporting groups |
| Overall Participants | 38 | 35 | 73 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
38
100%
|
35
100%
|
73
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
38.6
(12.7)
|
39.1
(11.9)
|
38.7
(12.2)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
20
52.6%
|
18
51.4%
|
38
52.1%
|
| Male |
18
47.4%
|
17
48.6%
|
35
47.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
38
100%
|
35
100%
|
73
100%
|
Outcome Measures
| Title | The Primary Outcome Measure Was Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores Over Weeks Between Groups. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Ziprasidone Arm | Placebo Arm |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 35 | 38 |
| Mean (95% Confidence Interval) [Scores on a scale] |
11.4
|
5.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ziprasidone Arm, Placebo Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.4 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 10.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Placebo Arm | Geodon Arm | ||
| Arm/Group Description | 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). | 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). | ||
All Cause Mortality |
||||
| Placebo Arm | Geodon Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo Arm | Geodon Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/38 (0%) | 0/35 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo Arm | Geodon Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/38 (7.9%) | 3/35 (8.6%) | ||
| General disorders | ||||
| chest pain | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 |
| sedation | 0/38 (0%) | 0 | 2/35 (5.7%) | 2 |
| migraines | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 |
| Psychiatric disorders | ||||
| akathesia | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | S. Nassir Ghaemi, MD, MPH |
|---|---|
| Organization | Tufts Medical Center |
| Phone | 617-636-5735 |
| nghaemi@tuftsmedicalcenter.org |
- GA128000