A 12-Week, Placebo Controlled Trial of Ziprasidone as Monotherapy for Major Depressive Disorder (Geodon)

• ClinicalTrials.gov Identifier: NCT00555997
• Recruitment Status: Completed
• First Posted: November 9, 2007
• Results First Posted: July 3, 2014
• Last Update Posted: July 3, 2014
• Sponsor: Massachusetts General Hospital
• Collaborators: Cambridge Health Alliance; University of Connecticut; Vanderbilt University; Psychiatric Medicine Associates, L.L.C.; Cedars-Sinai Medical Center
• Information provided by (Responsible Party): George I. Papakostas, Massachusetts General Hospital

Study Description

Brief Summary:

This is a study on the effectiveness, tolerability and safety of oral ziprasidone as monotherapy in patients with major depressive disorder (MDD). Outpatients suffering from MDD will be treated with either ziprasidone or placebo for 12 weeks.

Hypothesis: There will be a statistically significant difference in the magnitude of response, as measured by a decrease in baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores, between the two treatment groups; the reduction in HAM-D-17 scores will be greater in the ziprasidone monotherapy group than in the placebo group.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Ziprasidone; Drug: Placebo	Phase 2

Detailed Description:

Exploratory hypothesis 1: There will be a statistically significant difference in the percentage of responders in the two treatment groups; response rates will be significantly higher for the ziprasidone monotherapy compared to the placebo group.

Exploratory hypothesis 2: The change in 6-VAS-D scores during the trial will be highly correlated to the change in HAM-D-17 and QIDS-SR during the trial.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Sequential Trial of Ziprasidone as Monotherapy for Major Depressive Disorder
• Study Start Date: March 2008
• Actual Primary Completion Date: June 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; Patients in group 1 will receive Ziprasidone for the full 12 weeks of the study.	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.; Other Name: Geodon
Active Comparator: 2; Patients in Group 2 will receive placebo for the first 6 weeks of the study, then will receive Ziprasidone for the last 6 weeks.	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.; Other Name: Geodon
Placebo Comparator: 3; Patients in Group 3 will receive placebo for the full 12 weeks of the study.	Drug: Placebo; 0mg Placebo per day. "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo

Outcome Measures

Primary Outcome Measures :

1. Hamilton Depression Rating Scale (HAM-D-17) Scores [ Time Frame: 6 weeks ]
   Higher numbers represent more symptoms of a major depressive episode. Minimum is 0. Maximum is 52.

Secondary Outcome Measures :

1. Responder/Non-responder [ Time Frame: 6 weeks ]
   A responder during phase 1 or phase 2 is someone who demonstrated a 50% or greater decrease in HAMD-17 scores during phase 1 or phase 2 (corresponding).
2. Change in 6-VAS-D Scores During Each Phase. [ Time Frame: 6 weeks ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Age 18-65.
2. Written informed consent.
3. MDD, current according to the fourth version of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) as diagnosed by the Mini International Neuropsychiatric Interview (MINI; Sheehan et al, 1998).
4. Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR- Trivedi et al, 2004) score of at least 10 at both screen and baseline visits.

Exclusion Criteria:

1. Pregnant women.
2. Women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or a partner with vasectomy).
3. Treatment with antidepressants for 2 weeks prior to the screen visit. If interested in discontinuing their current medication, potential participants must discuss this possibility with the prescribing physician. Study doctors will not implement any form of treatment washout.
4. Patients who no longer meet DSM-IV criteria for MDD during the baseline visit, or patients who demonstrate a 25% or greater reduction in QIDS-SR scores, screening to baseline.
5. Serious suicide or homicide risk, as assessed by the evaluating clinician or a score of 4 on the third item of the HAM-D.
6. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
7. Patients who meet criteria for alcohol or substance dependence, active within the last month.
8. Any bipolar disorder (current or past).
9. Any psychotic disorder (current or past).
10. Psychotic features in the current episode or a history of psychotic features.
11. History of a seizure disorder.
12. Clinical or laboratory evidence of untreated hypothyroidism.
13. Patients requiring excluded medications (see table 1 for details).
14. Prior course of ziprasidone, or intolerance to ziprasidone at any dose.
15. Any investigational psychotropic drug within the last 3 months.
16. Patients with significant cardiac conduction problems on screening electrocardiogram such as atrial fibrillation, atrial flutter, atrio-ventricular block, prolonged or abnormal QTc interval (i.e. QTc>450msec), or prolonged QRS interval.
17. Patients who have suffered a myocardial infarction within the past 12 months, with uncompensated heart failure, or a history of QTc prolongation.
18. Patients with abnormal serum potassium or magnesium levels upon screening.
19. Patients currently taking other drugs that prolong the QTc including dofetilide, sotalol, quinidine, class Ia antiarrhythmics, class III antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron methylate, probucol or tacrolimus.
20. Patients who have failed to experience significant clinical improvement following 3 or more antidepressant trials of adequate duration (at least 6 weeks) and dose (minimal effective doses defined as: fluoxetine, paroxetine, citalopram 20mg; sertraline, fluvoxamine 50mg, escitalopram 10mg, paroxetine CR 25mg, venlafaxine 75mg, duloxetine 60mg, bupropion 150mg, 15mg of mirtazapine, trazodone or nefazodone 300mg).

Contacts and Locations

Locations

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

United States, Connecticut

University of Connecticut Health Center

Farmington, Connecticut, United States, 06030-6415

Comprehensive Psychiatric Care

Norwich, Connecticut, United States, 06360

United States, Illinois

Psychiatric Medicine Associates, L.L.C.

Chicago, Illinois, United States, 60612

United States, Massachusetts

Massachusetts General Hosptial

Boston, Massachusetts, United States, 02114

Cambridge Health Alliance

Cambridge, Massachusetts, United States, 02139

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37212

Sponsors and Collaborators

Massachusetts General Hospital

Cambridge Health Alliance

University of Connecticut

Vanderbilt University

Psychiatric Medicine Associates, L.L.C.

Cedars-Sinai Medical Center

Investigators

• Principal Investigator: George I Papakostas, M.D.; Massachusetts General Hospital
• Principal Investigator: John M Zajecka, M.D.; Psychiatric Medicine Associates, L.L.C.
• Principal Investigator: Richard C Shelton, M.D.; Vanderbilt University Medical Center
• Principal Investigator: Andrew Winokur, M.D.; UConn Health
• Principal Investigator: Gustavo Kinrys, M.D.; Cambridge Health Alliance
• Principal Investigator: Waguih IsHak, M.D.; Cedar's Sinai
• Principal Investigator: Mahmoud S Okasha, MD; Comprehensive Psychiatric Care, Norwich CT

More Information

Publications of Results:

Papakostas GI, Vitolo OV, Ishak WW, Rapaport MH, Zajecka JM, Kinrys G, Mischoulon D, Lipkin SH, Hails KA, Abrams J, Ward SG, Meisner A, Schoenfeld DA, Shelton RC, Winokur A, Okasha MS, Bari MA, Fava M. A 12-week, randomized, double-blind, placebo-controlled, sequential parallel comparison trial of ziprasidone as monotherapy for major depressive disorder. J Clin Psychiatry. 2012 Dec;73(12):1541-7. doi: 10.4088/JCP.12m07670.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Heo JY, Jeon HJ, Fava M, Mischoulon D, Baer L, Clain A, Doorley J, Pisoni A, Papakostas GI. Efficacy of ziprasidone monotherapy in patients with anxious depression: a 12-week, randomized, double-blind, placebo-controlled, sequential-parallel comparison trial. J Psychiatr Res. 2015 Mar;62:56-61. doi: 10.1016/j.jpsychires.2015.01.007. Epub 2015 Jan 26.

• Responsible Party: George I. Papakostas, Director of Treatment-Resistant Studies, Depression Clinical and Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00555997
• Obsolete Identifiers: NCT00657592
• Other Study ID Numbers: 2007-P-000623
• First Posted: November 9, 2007
• Results First Posted: July 3, 2014
• Last Update Posted: July 3, 2014
• Last Verified: June 2014

Keywords provided by George I. Papakostas, Massachusetts General Hospital:

Major Depressive Disorder; Major Depression; Depression; Geodon; Ziprasidone

Additional relevant MeSH terms:

Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Pathologic Processes; Mood Disorders; Mental Disorders; Behavioral Symptoms; 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