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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

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

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Arm Type

Experimental

Arm Description

Arm Title

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

Time Frame

8 Weeks

Secondary Outcome Measure Information:

Title

Remission Rates (HAM-D 17 Scores of Less Than 8) After Treatment Phase 2.

Description

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

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

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Ziprasidone Augmentation of SSRIs for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs

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