Back to resultsPredictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder
Primary Purpose
Depression, Bipolar Disorder
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
ziprasidone
Sugar pill
Sponsored by
About this trial
This is an interventional treatment trial for Depression focused on measuring Major Depressive Disorder, MDD, Bipolar Disorder, BD, Depression, Major Depressive Disorder with Bipolar features
Eligibility Criteria
Inclusion Criteria:
- Age 18-70 years.
- If female, nonpregnant/nonlactating
- 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 DSM-IV criteria for a major depressive episode, non-psychotic.
- Having at least 3 of the following criteria listed for predictors of depressive response to neuroleptics: a family history of bipolar disorder, antidepressant-induced mania, highly recurrent depressive episodes (>5), atypical depression, early age of onset of depression (< age 20), failure to respond to antidepressants, and antidepressant tolerance (initial response followed by later loss of response). Inadequate response to antidepressants is identified as follows: having a score of ≥14 on the 17-item HAMD or a CGI-S score of ≥ 3 after a retrospective confirmation of an adequate trial of a single antidepressant (defined as a ≥ 6-week trial of acceptable therapeutic dose [≥ 40 mg of fluoxetine, paroxetine or citalopram, 20 mg of escitalopram, 60 mg of duloxetine, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100 mg of fluvoxamine, 225 mg of venlafaxine XR, 30 mg of mirtazapine, 300 mg of bupropion, 75 mg of nortriptyline, 20 mg of protriptyline, 100 mg of amitriptyline or imipramine)
Exclusion Criteria:
- Bipolar depression
- Sensitivity to or failure to respond to ziprasidone by history or ziprasidone use in previous 3 months
- Active substance abuse or dependence in the previous 3 month
- Psychotic disorders
- Serious suicidality as evidenced by score of 3 or greater on suicide item of MADRS
- Medically unstable as judged by study investigators
- Lack of capacity to provide informed, written, consent to investigators
- Previous diagnosed cardiac arrhythmias
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Sugar pill
Ziprasidone
Arm Description
Patients are randomized to a sugar pill (placebo), added to their current medications.
Patients are randomized to ziprasidone, added to their current medications.
Outcomes
Primary Outcome Measures
MADRS Improvement Over 6 Weeks
Montgomery Asberg Depression scale improvement was assessed in two 6 week crossover periods.
Minimum score on MADRS is 0, the maximum is 60. Higher scores represent a worse outcome, i.e., greater severity of depressive symptoms.
Scores of about 20 and above are generally seen as consistent with being in a full major depressive episode.
No subscales were used or combined.
Secondary Outcome Measures
Predictors of Bipolarity to Define the Study Population
The specific bipolarity predictors in patients with MDD were assessed.
Full Information
NCT ID
NCT01168674
First Posted
July 21, 2010
Last Updated
February 21, 2017
Sponsor
Tufts Medical Center
Collaborators
Duke University, University of South Carolina
1. Study Identification
Unique Protocol Identification Number
NCT01168674
Brief Title
Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder
Official Title
Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder : A 13-week, Double-Blind, Placebo-Controlled, Cross-Over Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center
Collaborators
Duke University, University of South Carolina
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary outcome of this study is to determine if predictors of response can select a population of patients with MDD that is effectively treatable by augmentation with ziprasidone.
Major depressive disorder (MDD) is a broad category, including many forms of depressive illness, including those with only a single major depressive episode, those with episodic recurrence with intervening well states, those with chronic depressive/anxious states without intervening euthymia, and those with manic symptoms that do not meet threshold definitions of full mania/hypomania.
In this heterogenous, large diagnostic definition, important groups of patients do not appear to respond well to antidepressants, and, conversely, based on observational studies, may respond well to neuroleptics. These predictors of response have begun to be identified and may serve to better design studies of neuroleptics in depressive illnesses.
Among these predictors of response in MDD are clinical features that are more similar to bipolar illness than unipolar depression. These include a family history of bipolar disorder, antidepressant-induced mania, highly recurrent depressive episodes (>5), atypical depression, early age of onset of depression (< age 20), failure to respond to antidepressants, and antidepressant tolerance (initial response followed by later loss of response).
The investigators propose to use these predictors to pick out patients that are more likely to respond to Geodon for MDD. This will be the first RCT of these predictors of depressive response applied to neuroleptics.
Detailed Description
This will be a three-site, block randomized (1:1 ratio) double-blind, placebo-controlled prospective cross-over study with 50 subjects. Patients will be randomized to receiving ziprasidone-washout-placebo or placebo- washout-ziprasidone for 13-weeks.
Primary and Secondary and safety outcomes: The primary outcome measure will be change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) score to end of treatment. Safety outcomes will be determined by spontaneously reported adverse events on the case report form.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Bipolar Disorder
Keywords
Major Depressive Disorder, MDD, Bipolar Disorder, BD, Depression, Major Depressive Disorder with Bipolar features
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sugar pill
Arm Type
Placebo Comparator
Arm Description
Patients are randomized to a sugar pill (placebo), added to their current medications.
Arm Title
Ziprasidone
Arm Type
Active Comparator
Arm Description
Patients are randomized to ziprasidone, added to their current medications.
Intervention Type
Drug
Intervention Name(s)
ziprasidone
Other Intervention Name(s)
Geodon
Intervention Description
Ziprasidone will be administered as a pill. The once-daily total daily dose will be 80-160 mg/d of ziprasidone. Dosing will begin at 20 mg BID with an escalation strategy based on target symptoms and tolerability, with a target dose range of 80-160 mg/d. Dose escalations will occur by increments of 20-40 mg weekly.
Intervention Type
Drug
Intervention Name(s)
Sugar pill
Other Intervention Name(s)
Placebo
Intervention Description
The once-daily total daily dose will be 80-160 mg/d of the sugar pill. Dosing will begin at 20 mg BID with an escalation strategy based on target symptoms and tolerability, with a target dose range of 80-160 mg/d. Dose escalations will occur by increments of 20-40 mg weekly.
Primary Outcome Measure Information:
Title
MADRS Improvement Over 6 Weeks
Description
Montgomery Asberg Depression scale improvement was assessed in two 6 week crossover periods.
Minimum score on MADRS is 0, the maximum is 60. Higher scores represent a worse outcome, i.e., greater severity of depressive symptoms.
Scores of about 20 and above are generally seen as consistent with being in a full major depressive episode.
No subscales were used or combined.
Time Frame
13 weeks (Two 6 week periods plus a one week washout)
Secondary Outcome Measure Information:
Title
Predictors of Bipolarity to Define the Study Population
Description
The specific bipolarity predictors in patients with MDD were assessed.
Time Frame
13 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-70 years.
If female, nonpregnant/nonlactating
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 DSM-IV criteria for a major depressive episode, non-psychotic.
Having at least 3 of the following criteria listed for predictors of depressive response to neuroleptics: a family history of bipolar disorder, antidepressant-induced mania, highly recurrent depressive episodes (>5), atypical depression, early age of onset of depression (< age 20), failure to respond to antidepressants, and antidepressant tolerance (initial response followed by later loss of response). Inadequate response to antidepressants is identified as follows: having a score of ≥14 on the 17-item HAMD or a CGI-S score of ≥ 3 after a retrospective confirmation of an adequate trial of a single antidepressant (defined as a ≥ 6-week trial of acceptable therapeutic dose [≥ 40 mg of fluoxetine, paroxetine or citalopram, 20 mg of escitalopram, 60 mg of duloxetine, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100 mg of fluvoxamine, 225 mg of venlafaxine XR, 30 mg of mirtazapine, 300 mg of bupropion, 75 mg of nortriptyline, 20 mg of protriptyline, 100 mg of amitriptyline or imipramine)
Exclusion Criteria:
Bipolar depression
Sensitivity to or failure to respond to ziprasidone by history or ziprasidone use in previous 3 months
Active substance abuse or dependence in the previous 3 month
Psychotic disorders
Serious suicidality as evidenced by score of 3 or greater on suicide item of MADRS
Medically unstable as judged by study investigators
Lack of capacity to provide informed, written, consent to investigators
Previous diagnosed cardiac arrhythmias
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nassir Ghaemi, MD MPH
Organizational Affiliation
Tufts Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ashwin Patkar, MD
Organizational Affiliation
Duke
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Meera Narasimhan, MD
Organizational Affiliation
University of South Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Prakash Masand, MD
Organizational Affiliation
Duke
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder
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