Clinical trial NCT01168674
Conditions: Depression Bipolar Disorder
Keywords: Major Depressive Disorder MDD Bipolar Disorder BD Depression Major Depressive Disorder with Bipolar features
Sponsor: Tufts Medical Center
Start date: 2010-02-01; Completion date: 2011-12-01
Enrollment: 49 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief 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.

Arms: arm 1: Patients are randomized to a sugar pill (placebo), added to their current medications. arm 2: Patients are randomized to ziprasidone, added to their current medications.
Interventions: intervention 1: ziprasidone intervention 2: Sugar pill
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents: