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

NCT01168674 | Completed Phase 4 Results DMC

• 1 other identifier: 9238
• Study Type: interventional
• Target: 49
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Depression; Bipolar Disorder

Keywords

Major Depressive Disorder; MDD; Bipolar Disorder; BD; Depression; Major Depressive Disorder with Bipolar features

Outcome Measures

Primary Outcomes (1)

• MADRS Improvement Over 6 Weeks

  Montgomery Asberg Depression scale improvement was assessed in two 6 week crossover periods. Minimum score on MADRS is 0, the maximum is 60. Higher scores represent a worse outcome, i.e., greater severity of depressive symptoms. Scores of about 20 and above are generally seen as consistent with being in a full major depressive episode. No subscales were used or combined.

  13 weeks (Two 6 week periods plus a one week washout)

Secondary Outcomes (1)

• Predictors of Bipolarity to Define the Study Population

  13 weeks

Study Arms (2)

Sugar pill

PLACEBO COMPARATOR

Patients are randomized to a sugar pill (placebo), added to their current medications.

Drug: Sugar pill

Ziprasidone

ACTIVE COMPARATOR

Patients are randomized to ziprasidone, added to their current medications.

Drug: ziprasidone

Interventions

ziprasidone DRUG

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.

Also known as: Geodon

Ziprasidone

Sugar pill DRUG

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.

Also known as: Placebo

Sugar pill

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years.
• If female, nonpregnant/nonlactating
• If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation)
• Currently meets DSM-IV criteria for a major depressive episode, non-psychotic.
• 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)

You may not qualify if:

• Bipolar depression
• Sensitivity to or failure to respond to ziprasidone by history or ziprasidone use in previous 3 months
• Active substance abuse or dependence in the previous 3 month
• Psychotic disorders
• Serious suicidality as evidenced by score of 3 or greater on suicide item of MADRS
• Medically unstable as judged by study investigators
• Lack of capacity to provide informed, written, consent to investigators
• Previous diagnosed cardiac arrhythmias

Sponsors & Collaborators

• Tufts Medical Center: lead
• Duke University: collaborator
• University of South Carolina: collaborator

MeSH Terms

Conditions

Depression; Bipolar Disorder; Depressive Disorder, Major

Interventions

ziprasidone; Sugars

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Depressive Disorder

Intervention Hierarchy (Ancestors)

Carbohydrates

Limitations and Caveats

All crossover studies have the limitation of order effects: the order in which treatments were given could impact the results. The definition of bipolarity predictors also may not have effectively identified groups correctly.

Results Point of Contact

• Title: Dr. Nassir Ghaemi
• Organization: Tufts Medical Center

nghaemi@tuftsmedicalcenter.org

6176365735

Study Officials

• Nassir Ghaemi, MD MPH

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

• Ashwin Patkar, MD

  Duke

  PRINCIPAL INVESTIGATOR

• Meera Narasimhan, MD

  University of South Carolina

  PRINCIPAL INVESTIGATOR

• Prakash Masand, MD

  Duke

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2010
• First Posted: July 23, 2010
• Study Start: February 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 24, 2017
• Results First Posted: February 13, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share