Ziprasidone Augmentation of SSRIs for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs
Primary Purpose
Major Depressive Disorder
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ziprasidone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, Major Depression, Depression, Geodon, Ziprasidone, SSRI Augmentation, Treatment Resistant Depression
Eligibility Criteria
Inclusion Criteria:
- Written informed consent.
- Men or women, 18-65 years of age.
- MDD, current, according to DSM-IV criteria and as diagnosed by the SCID- I/P during the screen and baseline visit of phase 1.
- A HAM-D-17 score > 14 during the screen and baseline visit of phase 1.
Exclusion Criteria:
- Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine
- Device, tubal ligation, or partner with vasectomy).
- Serious suicide or homicide risk, as assessed by evaluating clinician.
- Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder.
- History of multiple adverse drug reactions or allergy to the study drug.
- The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past).
- Patients requiring excluded medications (see appendix 1 for details).
- Psychotic features in the current episode or a history of psychotic features.
- Prior course of ziprasidone, or intolerance to ziprasidone at any dose.
- Any investigational psychotropic drug within the last 3 months.
- Have failed more than 3 adequate antidepressant trials during the current MDE. Some examples of adequate dosage of an antidepressant trial include either > 150 mg of imipramine (or its tricyclic equivalent), > 60 mg of phenelzine (or its monoamine oxidase inhibitor equivalent), > 20 mg of fluoxetine (or its SSRI-equivalent), > 150mg of bupropion, > 300mg of trazodone (or nefazodone), >75 mg of venlafaxine, >60mg of duloxetine, or > 15mg of mirtazapine. A trial of adequate duration was defined as one during which the patient was on any given antidepressant at an adequate dose for a minimum of 6 weeks.
Sites / Locations
- University of Alabama at Birmingham
- Massachusetts General Hospital- Depression Clinical and Research Program
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
Patients in group 1 will receive Ziprasidone for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Ziprasidone for 12 months.
Patients in group 2 will receive Placebo for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Placebo for 12 months.
Outcomes
Primary Outcome Measures
The Primary Outcome Measure Will be Response Rates (50% Decrease in HAM-D-17 Scores) During Phase 2
The primary outcome measure will be response rates (50% decrease in HAM-D-17 scores) during phase 2. A responder will be a patient who experiences a 50% or greater decrease in symptoms according to the HAM-D-17 during phase 2.
Secondary Outcome Measures
Remission Rates (HAM-D 17 Scores of Less Than 8) After Treatment Phase 2.
A secondary outcome measure will be remission rates (HAM-D 17 scores of less than 8) after treatment phase 2.. A remitted will be a patient with a final score of 7 or less on the HAMD-17 during phase 2.
Comparing Scores on HAM-D 17 Baseline Visit to Phase 2 Final Visit at Week 8
This will involve looking at the change in HAM-D 17 scores during phase 2. For HAMD-17 the minimum is 0, the maximum is 52, and greater scores represent more symptoms.
Full Information
NCT ID
NCT00633399
First Posted
March 4, 2008
Last Updated
June 24, 2014
Sponsor
Massachusetts General Hospital
Collaborators
University of Alabama at Birmingham
1. Study Identification
Unique Protocol Identification Number
NCT00633399
Brief Title
Ziprasidone Augmentation of SSRIs for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs
Official Title
A Three-phase Study Designed to Test the Efficacy, Tolerability and Safety of the Combination of Ziprasidone With Selective Serotonin Reuptake Inhibitors (SSRI) for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
University of Alabama at Birmingham
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to see if adding the study drug, ziprasidone, to an antidepressant medication helps improve symptoms of Major Depressive Disorder (MDD). We are studying the drug's effectiveness in treating depression, as well as its safety when it is added to another drug.
Hypothesis A: There will be a difference in the percentage of responders in the two treatment conditions during phase 2; response rates will be higher for the ziprasidone group.
Detailed Description
The proposed study involves three phases. The first phase is an 8-week, open-label trial of an SSRI for MDD. Patients who do not experience sufficient symptom improvement following this open-label trial will be enrolled in a 6-week, double-blind, placebo controlled trial of ziprasidone augmentation (second phase). Ziprasidone and placebo-remitters will then enter a 12-month, double-blind extension phase (third phase). We estimate that approximately 400 patients will enter phase 1 of the study so that a minimum of 180 subjects will enter double-blind treatment (phase 2) over 5 years. Each treatment arm during phase 2 will have 90 subjects.
Hypothesis B1: During phase 2, there will be a difference between the two groups in the percentage of responders (50% or greater reduction in symptom severity) with regards to anxious symptoms of MDD as measured by the 14-item Hamilton Anxiety Rating Scale (HAM-A); response rates will be higher for the ziprasidone group.
Hypothesis B2: During phase 2, there will be a difference between the two groups in the percentage of responders (50% or greater reduction in symptom severity) with regards to painful symptoms of MDD, as measured by the overall visual analogue pain (VAS-pain) scale scores; response rates will be higher for the ziprasidone group.
Hypothesis C: The time to relapse during phase 3 will be shorter among adjunctive placebo- than ziprasidone-remitters.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Major Depressive Disorder, Major Depression, Depression, Geodon, Ziprasidone, SSRI Augmentation, Treatment Resistant Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
458 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Patients in group 1 will receive Ziprasidone for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Ziprasidone for 12 months.
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Patients in group 2 will receive Placebo for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Placebo for 12 months.
Intervention Type
Drug
Intervention Name(s)
Ziprasidone
Other Intervention Name(s)
Geodon
Intervention Description
20mg-80mg a day. Dose increases of 20mg per day may occur at three study visits as directed by clinician. Maximum; 80mg per day per patient.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0mg Placebo per day (1-4 tablets per day). "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo.
Primary Outcome Measure Information:
Title
The Primary Outcome Measure Will be Response Rates (50% Decrease in HAM-D-17 Scores) During Phase 2
Description
The primary outcome measure will be response rates (50% decrease in HAM-D-17 scores) during phase 2. A responder will be a patient who experiences a 50% or greater decrease in symptoms according to the HAM-D-17 during phase 2.
Time Frame
8 Weeks
Secondary Outcome Measure Information:
Title
Remission Rates (HAM-D 17 Scores of Less Than 8) After Treatment Phase 2.
Description
A secondary outcome measure will be remission rates (HAM-D 17 scores of less than 8) after treatment phase 2.. A remitted will be a patient with a final score of 7 or less on the HAMD-17 during phase 2.
Time Frame
8 weeks
Title
Comparing Scores on HAM-D 17 Baseline Visit to Phase 2 Final Visit at Week 8
Description
This will involve looking at the change in HAM-D 17 scores during phase 2. For HAMD-17 the minimum is 0, the maximum is 52, and greater scores represent more symptoms.
Time Frame
8 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:
Written informed consent.
Men or women, 18-65 years of age.
MDD, current, according to DSM-IV criteria and as diagnosed by the SCID- I/P during the screen and baseline visit of phase 1.
A HAM-D-17 score > 14 during the screen and baseline visit of phase 1.
Exclusion Criteria:
Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine
Device, tubal ligation, or partner with vasectomy).
Serious suicide or homicide risk, as assessed by evaluating clinician.
Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder.
History of multiple adverse drug reactions or allergy to the study drug.
The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past).
Patients requiring excluded medications (see appendix 1 for details).
Psychotic features in the current episode or a history of psychotic features.
Prior course of ziprasidone, or intolerance to ziprasidone at any dose.
Any investigational psychotropic drug within the last 3 months.
Have failed more than 3 adequate antidepressant trials during the current MDE. Some examples of adequate dosage of an antidepressant trial include either > 150 mg of imipramine (or its tricyclic equivalent), > 60 mg of phenelzine (or its monoamine oxidase inhibitor equivalent), > 20 mg of fluoxetine (or its SSRI-equivalent), > 150mg of bupropion, > 300mg of trazodone (or nefazodone), >75 mg of venlafaxine, >60mg of duloxetine, or > 15mg of mirtazapine. A trial of adequate duration was defined as one during which the patient was on any given antidepressant at an adequate dose for a minimum of 6 weeks.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George I Papakostas, M.D.
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Massachusetts General Hospital- Depression Clinical and Research Program
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27835715
Citation
Mischoulon D, Shelton RC, Baer L, Bobo WV, Curren L, Fava M, Papakostas GI. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Cardiac, Endocrine, Metabolic, and Motoric Effects in a Randomized, Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. 2017 Apr;78(4):449-455. doi: 10.4088/JCP.15m10426.
Results Reference
derived
PubMed Identifier
27306192
Citation
Ionescu DF, Shelton RC, Baer L, Meade KH, Swee MB, Fava M, Papakostas GI. Ziprasidone augmentation for anxious depression. Int Clin Psychopharmacol. 2016 Nov;31(6):341-6. doi: 10.1097/YIC.0000000000000133.
Results Reference
derived
PubMed Identifier
26085041
Citation
Papakostas GI, Fava M, Baer L, Swee MB, Jaeger A, Bobo WV, Shelton RC. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study. Am J Psychiatry. 2015 Dec;172(12):1251-8. doi: 10.1176/appi.ajp.2015.14101251. Epub 2015 Jun 18.
Results Reference
derived
Learn more about this trial
Ziprasidone Augmentation of SSRIs for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs
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