Overview

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

Status:
Completed
Trial end date:
2010-06-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Massachusetts General Hospital
Collaborators:
Cambridge Health Alliance
Cedars-Sinai Medical Center
Psychiatric Medicine Associates, L.L.C.
University of Connecticut
Vanderbilt University
Vanderbilt University Medical Center
Treatments:
Ziprasidone
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).