Bipolar II Disorder, Major Depressive Episode
Conditions
Keywords
Bipolar II Disorder, Major Depressive Episode
Brief summary
The purpose of this study is to evaluate the antidepressant effectiveness of Geodon for the treatment of patients diagnosed with Bipolar II disorder who are currently experiencing a major depressive episode.
Detailed description
Bipolar II disorder is largely unstudied, with much less known about its treatment in comparison to Bipolar I disorder. While established mood stabilizers treat and prevent subsequent episodes of hypomania, chronic or recurrent depressions are harder to treat or prevent. In general the treatment of depression in Bipolar II patients is often complicated and there is no clinical unanimity on what approaches to follow. Administration of proven antidepressants would seem most appropriate and are most often used, but their use often involves a number of difficulties. Among these are: * antidepressant efficacy is established for unipolar patients and extrapolation to Bipolar II patients is done without empirical support * Bipolar II patients can have switches into hypomanic behavior in response to antidepressant treatment given as monotherapy * even when mood stabilizers are concomitantly given, switches to hypomanic states still occur when antidepressants are added * antidepressants can cause cycle acceleration or induce rapid cycling when given to Bipolar II patients * non-response and loss of response are common reactions to antidepressants in Bipolar II patients This study will also assess the tolerability of Geodon in the treatment of patients diagnosed with Bipolar II disorder who currently meet criteria for a Major Depressive Episode by examining the incidence of adverse events and the withdrawal rate due to adverse events. This will be an open-label study. Subjects will be treated for 8 weeks with Geodon, starting at a dose of 20 mg twice per day. The maximum dose will be 60 mg twice per day. Subjects will have a physical exam, electrocardiogram (ECG), standard laboratory tests and a urine drug screen at the screen visit. Efficacy evaluations will include 17-item Hamilton Depression Scale, Hamilton Anxiety Scale (HAM-D), Montgomery-Asberg Depression Rating Scale, and the Young Mania Rating Scale. Social outcome will be measured with a quality-of-life scale (the Q-LES-Q). Overall efficacy will be rated using the Clinical Global Severity and Improvement Scales.
Interventions
DRUGZiprasidone
Ziprasidone 20-60 mg BID, taken orally.
Sponsors
Liebowitz, Michael R., M.D.
Pfizer
The Medical Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients will meet DSM-IV criteria for Bipolar II Disorder, with at least one hypomanic episode as documented in the medical history or provided by an informant, or have evidence of a clear diagnosis of hypomania * patients will currently be experiencing a major depressive episode of 2 or more weeks, but less than 12 months duration * minimum score of 18 on the 17-item HAM-D at screen and baseline
Exclusion criteria
* patients will not meet criteria for Bipolar I or Schizoaffective Disorder or Schizophrenia * patients may have co-morbid anxiety or other Axis I disorders as long as depression dominates the clinical picture * Suicidal ideation or history that makes participation in a clinical trial unduly risky * unstable medical conditions or any abnormality in thyroid function * patients with a QTc of 450msec or greater on the initial ECG * patients requiring concomitant psychotropic drugs will not be eligible, although patients on such drugs who can undergo washout will be eligible. such patients must have discontinued psychoactive drugs at least 2 weeks before beginning study, with 4 weeks for fluoxetine and depot neuroleptics * the use of Zolpidem 5-10 mg as needed will be permitted for patients suffering from insomnia, but cannot be taken the night before a scheduled assessment * patients with dementia or substance abuse in the last 6 months * pregnant or lactating women will be excluded, as will those not using adequate forms of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Efficacy Endpoint is the Comparison of Baseline and Week 8 Endpoint in the 17-item HAM-D Total Scores | Week 8 | Hamilton Depression Rating Scale, measuring depression symptoms; possible total scores ranging from 0-54, with higher scores indicating greater severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Hamilton Anxiety Scale (HAM-A) | Week 8 | Hamilton Anxiety Rating Scale, measuring anxiety symptoms; possible total scores ranging from 0-30, with higher scores indicating greater severity of anxiety. |
| Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale | Week 8 | Montgomery-Åsberg Depression Rating Scale, measuring depression symptoms; possible total scores ranging from 0-60, with higher scores indicating greater severity of depression. |
| Percentage of Subjects With Clinical Global Inventory (CGI) Global Improvement Score of 1 or 2 | Week 8 | Clinical Global Impression of Improvement scale: one item, measuring overall improvement of illness; possible scores range from 1-7, with lower scores representing greater improvement. 18 subjects (60%) were responders (defined as having a CGI-I scores of 1 or 2 at Week 8/study endpoint) by the end of the trial. |
| Mean Change From Baseline in the CGI-Severity of Illness (CGI-S) Score at Study Endpoint | Week 8 | Clinical Global Impression of Severity scale: one item, measuring overall severity of illness; possible scores range from 1-7, with higher scores representing greater severity of illness. |
| Mean Change From Baseline in the Total Score of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Week 8 | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scale consists of 14 items; possible scores range from 14-70 with higher scores indicating greater quality of life and satisfaction. |
| Mean Change From Baseline in the Total Score of the Beck Depression Inventory (BDI) | Week 8 | Beck Depression Inventory, self-rated scale measuring depression symptoms; possible total scores ranging from 0-63, with higher scores indicating greater severity of depression. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at three research centers, located in: New York, NY; Plano, TX; and Seattle, WA. Subjects were recruited over a 37 month period.
Pre-assignment details
The planned and actual study population was 30 patients, 18 years of age or older, who met DSM-IV criteria for bipolar II disorder with a history of at least one hypomanic episode.
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Ziprasidone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age Continuous | 38.61 years STANDARD_DEVIATION 13.34 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 30 |
| serious Total, serious adverse events | 1 / 30 |
Outcome results
Primary
The Primary Efficacy Endpoint is the Comparison of Baseline and Week 8 Endpoint in the 17-item HAM-D Total Scores
Hamilton Depression Rating Scale, measuring depression symptoms; possible total scores ranging from 0-54, with higher scores indicating greater severity of symptoms.
Time frame: Week 8
Population: Per protocol, the number of participants for analysis was 30 randomized subjects; data analyzed at Week 8 or Last Observation Carried Forward for the 6 subjects who dropped out before completion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | The Primary Efficacy Endpoint is the Comparison of Baseline and Week 8 Endpoint in the 17-item HAM-D Total Scores | Baseline HAM-D | 23.1 Scores on a scale | Standard Deviation 3.49 |
| Ziprasidone | The Primary Efficacy Endpoint is the Comparison of Baseline and Week 8 Endpoint in the 17-item HAM-D Total Scores | Week 8 HAM-D | 10.57 Scores on a scale | Standard Deviation 7.61 |
p-value: <0.0001t-test, 2 sided
Secondary
Mean Change From Baseline in the CGI-Severity of Illness (CGI-S) Score at Study Endpoint
Clinical Global Impression of Severity scale: one item, measuring overall severity of illness; possible scores range from 1-7, with higher scores representing greater severity of illness.
Time frame: Week 8
Population: Per protocol, the number of participants for analysis was 30 randomized subjects; data analyzed at Week 8 or Last Observation Carried Forward for the 6 subjects who dropped out before completion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Mean Change From Baseline in the CGI-Severity of Illness (CGI-S) Score at Study Endpoint | Baseline CGI-S | 4.27 Score on a scale | Standard Deviation 0.42 |
| Ziprasidone | Mean Change From Baseline in the CGI-Severity of Illness (CGI-S) Score at Study Endpoint | Week 8 CGI-S | 2.33 Score on a scale | Standard Deviation 1.13 |
Secondary
Mean Change From Baseline in the Hamilton Anxiety Scale (HAM-A)
Hamilton Anxiety Rating Scale, measuring anxiety symptoms; possible total scores ranging from 0-30, with higher scores indicating greater severity of anxiety.
Time frame: Week 8
Population: Per protocol, the number of participants for analysis was 30 randomized subjects; data analyzed at Week 8 or Last Observation Carried Forward for the 6 subjects who dropped out before completion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Mean Change From Baseline in the Hamilton Anxiety Scale (HAM-A) | Baseline HAM-A | 19.47 Scores on a scale | Standard Deviation 4.1 |
| Ziprasidone | Mean Change From Baseline in the Hamilton Anxiety Scale (HAM-A) | Week 8 HAM-A | 10.69 Scores on a scale | Standard Deviation 7.09 |
Secondary
Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale
Montgomery-Åsberg Depression Rating Scale, measuring depression symptoms; possible total scores ranging from 0-60, with higher scores indicating greater severity of depression.
Time frame: Week 8
Population: Per protocol, the number of participants for analysis was 30 randomized subjects; data analyzed at Week 8 or Last Observation Carried Forward for the 6 subjects who dropped out before completion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale | Baseline MADRS | 28.47 Scores on a scale | Standard Deviation 4.96 |
| Ziprasidone | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale | Week 8 MADRS | 13.21 Scores on a scale | Standard Deviation 8.99 |
Secondary
Mean Change From Baseline in the Total Score of the Beck Depression Inventory (BDI)
Beck Depression Inventory, self-rated scale measuring depression symptoms; possible total scores ranging from 0-63, with higher scores indicating greater severity of depression.
Time frame: Week 8
Population: Per protocol, the number of participants for analysis was 30 randomized subjects; data analyzed at Week 8 or Last Observation Carried Forward for the 6 subjects who dropped out before completion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Mean Change From Baseline in the Total Score of the Beck Depression Inventory (BDI) | Baseline BDI | 27.9 Scores on a scale | Standard Deviation 9.78 |
| Ziprasidone | Mean Change From Baseline in the Total Score of the Beck Depression Inventory (BDI) | Week 8 BDI | 15.0 Scores on a scale | Standard Deviation 11.82 |
Secondary
Mean Change From Baseline in the Total Score of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scale consists of 14 items; possible scores range from 14-70 with higher scores indicating greater quality of life and satisfaction.
Time frame: Week 8
Population: Per protocol, the number of participants for analysis was 30 randomized subjects; data analyzed at Week 8 or Last Observation Carried Forward for the 6 subjects who dropped out before completion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Mean Change From Baseline in the Total Score of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Baseline Q-LES-Q | 35.07 Scores on a scale | Standard Deviation 7.34 |
| Ziprasidone | Mean Change From Baseline in the Total Score of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Week 8 Q-LES-Q | 48.25 Scores on a scale | Standard Deviation 12.97 |
Secondary
Percentage of Subjects With Clinical Global Inventory (CGI) Global Improvement Score of 1 or 2
Clinical Global Impression of Improvement scale: one item, measuring overall improvement of illness; possible scores range from 1-7, with lower scores representing greater improvement. 18 subjects (60%) were responders (defined as having a CGI-I scores of 1 or 2 at Week 8/study endpoint) by the end of the trial.
Time frame: Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ziprasidone | Percentage of Subjects With Clinical Global Inventory (CGI) Global Improvement Score of 1 or 2 | 60 percentage of subjects with CGI-I </=2 |