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

Sponsors and Collaborators:	Massachusetts General Hospital Vanderbilt University
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00633399

Purpose

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.

Condition	Intervention	Phase
Major Depressive Disorder	Drug: Ziprasidone Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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.

Resource links provided by NLM:

MedlinePlus related topics: Depression

Drug Information available for: Serotonin Ziprasidone hydrochloride Ziprasidone Ziprasidone mesylate

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

The primary outcome measure will be response rates (50% decrease in HAM-D-17 scores) during phase 2 [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Remission rates (HAM-D 17 scores of less than 8) after treatment phase 2. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Comparing scores on HAM-D 17, QIDS-SR and CGI from Phase 2 baseline visit to Phase 2 final visit at week 8 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	400
Study Start Date:	July 2008
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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.	Drug: Ziprasidone 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.
2: Placebo Comparator 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.	Drug: Placebo 0mg Placebo per day (1-4 tablets per day). "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo.

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00633399

Contacts

Contact: Soo Jeong Youn, BA	617-724-2936	syoun@partners.org
Contact: George I Papakostas, MD	617-726-6697	gpapakostas@partners.org

Locations

United States, Massachusetts
Massachusetts General Hospital- Depression Clinical and Research Program	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Victoria Ameral, BA 617-724-9458 vameral@partners.org
Contact: George I Papakostas, MD 617-726-6697 gpapakostas@partners.org
Principal Investigator: George I Papakostas, MD
United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Richard C Shelton, M.D. richard.shelton@vanderbilt.edu
Principal Investigator: Richard C Shelton, M.D.

Sponsors and Collaborators

Massachusetts General Hospital

Vanderbilt University

Investigators

Principal Investigator:

George I Papakostas, M.D.

Massachusetts General Hospital

More Information

Additional Information:

Depression Clinical and Research Program at MGH This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Massachusetts General Hospital, Boston, MA 02114 ( George I Papakostas, M.D. )
Study ID Numbers:	2007-P-002361
Study First Received:	March 4, 2008
Last Updated:	August 7, 2009
ClinicalTrials.gov Identifier:	NCT00633399 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

Major Depressive Disorder
Major Depression
Depression
Geodon

Ziprasidone
SSRI Augmentation
Treatment Resistant Depression

Study placed in the following topic categories:

Neurotransmitter Agents
Depression
Tranquilizing Agents
Psychotropic Drugs
Central Nervous System Depressants
Depressive Disorder, Major
Depressive Disorder
Antipsychotic Agents

Serotonin Uptake Inhibitors
Serotonin
Behavioral Symptoms
Dopamine
Mental Disorders
Mood Disorders
Dopamine Agents
Ziprasidone

Additional relevant MeSH terms:

Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Depressive Disorder, Major
Serotonin Antagonists
Pathologic Processes
Mental Disorders
Therapeutic Uses
Disease
Depression
Tranquilizing Agents

Central Nervous System Depressants
Dopamine Antagonists
Depressive Disorder
Antipsychotic Agents
Serotonin Uptake Inhibitors
Pharmacologic Actions
Behavioral Symptoms
Serotonin Agents
Mood Disorders
Dopamine Agents
Ziprasidone
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 10, 2009