Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder

Status:	Completed
Conditions:	Depression, Major Depression Disorder (MDD), Psychiatric
Therapuetic Areas:	Psychiatry / Psychology, Pulmonary / Respiratory Diseases
Healthy:	No
Age Range:	Any
Updated:	11/18/2012
Start Date:	February 2010
End Date:	December 2011

Predictors of Response to Augmentation With Ziprasidone (Geodon®) in Major Depressive Disorder : A 13-week, Double-Blind, Placebo-Controlled, Cross-Over Trial

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.

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; the
secondary efficacy measure will be changes in other efficacy ratings (HAM-A, and CGI) along
with changes in scales to measure functional improvement and quality of life (GAF). Safety
outcomes will be determined by the BAS and SAS ratings and spontaneously reported adverse
events on the case report form.

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

We found this trial at

sites

Duke University School of Medicine

Durham, North Carolina 27710

from

Durham, NC