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
Intervention: ziprasidone; Sugar pill
Intervention description: 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.
Intervention MeSH terms: Ziprasidone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Major Depressive Disorder; MDD; Bipolar Disorder; BD; Depression; Major Depressive Disorder with Bipolar features

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-70 years.

          2. If female, nonpregnant/nonlactating

          3. If a sexually active female of reproductive potential, must be using adequate
             contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation)

          4. Currently meets DSM-IV criteria for a major depressive episode, non-psychotic.

          5. Having at least 3 of the following criteria listed for predictors of depressive
             response to neuroleptics: 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).
             Inadequate response to antidepressants is identified as follows: having a score of ≥14
             on the 17-item HAMD or a CGI-S score of ≥ 3 after a retrospective confirmation of an
             adequate trial of a single antidepressant (defined as a ≥ 6-week trial of acceptable
             therapeutic dose [≥ 40 mg of fluoxetine, paroxetine or citalopram, 20 mg of
             escitalopram, 60 mg of duloxetine, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100
             mg of fluvoxamine, 225 mg of venlafaxine XR, 30 mg of mirtazapine, 300 mg of
             bupropion, 75 mg of nortriptyline, 20 mg of protriptyline, 100 mg of amitriptyline or
             imipramine)

        Exclusion Criteria:

          1. Bipolar depression

          2. Sensitivity to or failure to respond to ziprasidone by history or ziprasidone use in
             previous 3 months

          3. Active substance abuse or dependence in the previous 3 month

          4. Psychotic disorders

          5. Serious suicidality as evidenced by score of 3 or greater on suicide item of MADRS

          6. Medically unstable as judged by study investigators

          7. Lack of capacity to provide informed, written, consent to investigators

          8. Previous diagnosed cardiac arrhythmias