Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder
|ClinicalTrials.gov Identifier: NCT01168674|
Recruitment Status : Completed
First Posted : July 23, 2010
Results First Posted : February 13, 2017
Last Update Posted : February 24, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Depression Bipolar Disorder||Drug: ziprasidone Drug: Sugar pill||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||49 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|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 Start Date :||February 2010|
|Primary Completion Date :||December 2011|
|Study Completion Date :||December 2011|
Placebo Comparator: Sugar pill
Patients are randomized to a sugar pill (placebo), added to their current medications.
Drug: Sugar pill
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.
Other Name: Placebo
Active Comparator: Ziprasidone
Patients are randomized to ziprasidone, added to their current medications.
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.
Other Name: Geodon
- MADRS Improvement Over 6 Weeks [ Time Frame: 13 weeks (Two 6 week periods plus a one week washout) ]
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.
- Predictors of Bipolarity to Define the Study Population [ Time Frame: 13 weeks ]The specific bipolarity predictors in patients with MDD were assessed.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01168674
|Principal Investigator:||Nassir Ghaemi, MD MPH||Tufts Medical Center|
|Principal Investigator:||Ashwin Patkar, MD||Duke|
|Principal Investigator:||Meera Narasimhan, MD||University of South Carolina|
|Principal Investigator:||Prakash Masand, MD||Duke|