Open-Label Study of Geodon in Non-Rapid Cycling Bipolar II Patients With Major Depression

Study Overview
=================
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.

Official Title
-----------------
An Open-Label, Flexible-Dose Trial of the Safety and Efficacy of Geodon in Non-Rapid-Cycling Bipolar II Patients With Major Depression

Conditions
-----------------
Bipolar II Disorder, Major Depressive Episode

Intervention / Treatment
-----------------
* Drug: Ziprasidone


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ziprasidone<br>Ziprasidone monotherapy, 20-60 mg BID. | Drug: Ziprasidone<br>* Ziprasidone 20-60 mg BID, taken orally.<br>* Other names: Geodon;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 8 | 
| 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. | Week 8 | 
| 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. | Week 8 | 
| 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. | Week 8 | 
| 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. | Week 8 | 
| 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. | Week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bipolar II Disorder, Major Depressive Episode