A 12-Week, Placebo Controlled Trial of Ziprasidone as Monotherapy for Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Ziprasidone; Ziprasidone; Placebo
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.; 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.; 0mg Placebo per day. "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo
Intervention MeSH terms: Ziprasidone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 120.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Major Depressive Disorder; Major Depression; Depression; Geodon; Ziprasidone

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.
    

Eligibility 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).