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Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder

This study has been completed.
Sponsor:
Collaborators:
Duke University
University of South Carolina
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT01168674
First received: July 21, 2010
Last updated: December 20, 2016
Last verified: December 2016
  Purpose

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 Intervention Phase
Depression
Bipolar Disorder
Drug: ziprasidone
Drug: Sugar pill
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder : A 13-week, Double-Blind, Placebo-Controlled, Cross-Over Trial

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • Predictors of Bipolarity to Define the Study Population [ Time Frame: 13 weeks ]
    The specific bipolarity predictors in patients with MDD were assessed.


Enrollment: 49
Study Start Date: February 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: ziprasidone
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-70 years.
  2. If female, nonpregnant/nonlactating
  3. If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation)
  4. Currently meets DSM-IV criteria for a major depressive episode, non-psychotic.
  5. 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:

  1. Bipolar depression
  2. Sensitivity to or failure to respond to ziprasidone by history or ziprasidone use in previous 3 months
  3. Active substance abuse or dependence in the previous 3 month
  4. Psychotic disorders
  5. Serious suicidality as evidenced by score of 3 or greater on suicide item of MADRS
  6. Medically unstable as judged by study investigators
  7. Lack of capacity to provide informed, written, consent to investigators
  8. Previous diagnosed cardiac arrhythmias
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01168674

Sponsors and Collaborators
Tufts Medical Center
Duke University
University of South Carolina
Investigators
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
  More Information

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT01168674     History of Changes
Other Study ID Numbers: 9238 
Study First Received: July 21, 2010
Results First Received: May 13, 2015
Last Updated: December 20, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Tufts Medical Center:
Major Depressive Disorder
MDD
Bipolar Disorder
BD
Depression
Major Depressive Disorder with Bipolar features

Additional relevant MeSH terms:
Depression
Disease
Depressive Disorder
Depressive Disorder, Major
Bipolar Disorder
Behavioral Symptoms
Pathologic Processes
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Ziprasidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on February 20, 2017