Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder
Condition: Depression; Bipolar Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Bipolar Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary outcome of this study is to determine if predictors of response can select a
      population of patients with MDD that is effectively treatable by augmentation with
      ziprasidone.

      Major depressive disorder (MDD) is a broad category, including many forms of depressive
      illness, including those with only a single major depressive episode, those with episodic
      recurrence with intervening well states, those with chronic depressive/anxious states without
      intervening euthymia, and those with manic symptoms that do not meet threshold definitions of
      full mania/hypomania.

      In this heterogenous, large diagnostic definition, important groups of patients do not appear
      to respond well to antidepressants, and, conversely, based on observational studies, may
      respond well to neuroleptics. These predictors of response have begun to be identified and
      may serve to better design studies of neuroleptics in depressive illnesses.

      Among these predictors of response in MDD are clinical features that are more similar to
      bipolar illness than unipolar depression. These include a family history of bipolar disorder,
      antidepressant-induced mania, highly recurrent depressive episodes (>5), atypical depression,
      early age of onset of depression (< age 20), failure to respond to antidepressants, and
      antidepressant tolerance (initial response followed by later loss of response).

      The investigators propose to use these predictors to pick out patients that are more likely
      to respond to Geodon for MDD. This will be the first RCT of these predictors of depressive
      response applied to neuroleptics.
    

Detailed description: 
      This will be a three-site, block randomized (1:1 ratio) double-blind, placebo-controlled
      prospective cross-over study with 50 subjects. Patients will be randomized to receiving
      ziprasidone-washout-placebo or placebo- washout-ziprasidone for 13-weeks.

      Primary and Secondary and safety outcomes: The primary outcome measure will be change from
      baseline Montgomery-Asberg Depression Rating Scale (MADRS) score to end of treatment. Safety
      outcomes will be determined by spontaneously reported adverse events on the case report form.
    

Intervention name(s): ziprasidone; Sugar pill
Intervention type(s): Drug; Drug
Intervention description(s): Ziprasidone will be administered as a pill. The once-daily total daily dose will be 80-160 mg/d of ziprasidone. Dosing will begin at 20 mg BID with an escalation strategy based on target symptoms and tolerability, with a target dose range of 80-160 mg/d. Dose escalations will occur by increments of 20-40 mg weekly.; The once-daily total daily dose will be 80-160 mg/d of the sugar pill. Dosing will begin at 20 mg BID with an escalation strategy based on target symptoms and tolerability, with a target dose range of 80-160 mg/d. Dose escalations will occur by increments of 20-40 mg weekly.
Other intervention name(s): Geodon; Placebo
Intervention MeSH terms: Ziprasidone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Major Depressive Disorder; MDD; Bipolar Disorder; BD; Depression; Major Depressive Disorder with Bipolar features