Ziprasidone for the Treatment of Generalized Anxiety in Patients With Bipolar Disorder

March 20, 2014 updated by: Naomi M. Simon, Massachusetts General Hospital

Ziprasidone for the Treatment of Generalized Anxiety Comorbidity in Patients With Bipolar Disorder

This study proposes to examine the potential safety and efficacy of ziprasidone for patients with anxiety and bipolar disorder on anxiety outcomes, bipolar symptoms, and on measures of quality of life and resilience.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study would be the first prospective, placebo-controlled study to our knowledge of any pharmacotherapy strategy for the treatment of comorbid generalized anxiety (or any comorbid anxiety) in patients with bipolar disorder. Our hypotheses are:

  1. Ziprasidone flexibly dosed from 40 to 160 mg/day will reduce anxiety symptoms significantly more than placebo in patients with bipolar disorder who have a full or subsyndromal diagnosis of generalized anxiety disorder (GAD).
  2. Ziprasidone will be well tolerated in patients with generalized anxiety based on the incidence of treatment emergent adverse effects during 8 weeks of therapy, and based on a lack of worsening of bipolar depression, mania or hypomania compared to placebo.
  3. Treatment with ziprasidone will have a significantly greater positive impact on measures of quality of life and resilience than placebo.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female outpatients, aged 18 to 75 years.
  • Diagnosis of Bipolar Disorder (Bipolar I or Bipolar II).
  • Current diagnosis of Generalized Anxiety Disorder (GAD).
  • Participants must be on at least one of the following mood stabilizers at steady dose for at least 4 weeks prior to randomization: lithium with blood levels between 0.4-1.4 meq/L, valproic acid/divalproate sodium (with levels between 50-150 ugm/dl) carbamazepine (blood levels between 4-12 mcg/ml), or lamotrigine (dosed 50-400 mg/day).

Exclusion Criteria:

  • Pregnant or lactating women or others not using acceptable means of birth control (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, implanted progesterone rods stabilized for at least 3 months).
  • Patients with current or history of schizophrenia, or patients with current mania, hypomania at study entry. Lifetime psychosis and dementia are exclusionary.
  • Patients with current obsessive-compulsive disorder or posttraumatic stress disorder are excluded.
  • Patients with a history of alcohol or substance abuse or dependence within the last three months.
  • Patients with significant unstable medical illness likely to result in hospitalization or acute medical care. In addition, patients with an established diagnosis of diabetes mellitus are excluded.
  • Current cognitive behavioral therapy directed toward the treatment of generalized anxiety disorder.
  • History of hypersensitivity to or lack of response to ziprasidone.
  • Concomitant treatment with other typical or atypical antipsychotics; patients should be off other typical or atypical antipsychotics for at least one week prior to study baseline.
  • Patients with significant suicidal ideation or who have enacted suicidal behaviors within 3 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
  • Patients who have had a psychiatric hospitalization (including for bipolar disorder) in the past 3 months are excluded.
  • Seizure disorders with the exception of a history of febrile seizures if they occurred during childhood, were isolated, and did not recur in adulthood.
  • History of Neuroleptic Malignant Syndrome.
  • Individuals with current clinically significant orthostatic hypotension are excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ziprasidone
Ziprasidone will be dosed on a twice daily (BID) basis, with flexible dosing based on tolerability, with a total daily dose in the range of 40 to 160 mg/day, for 8 weeks. This time period reflects the rapid onset of effect seen in studies of atypical antipsychotics, but allows time for a potentially longer response for some anxiety symptoms.
Drug: Ziprasidone
Ziprasidone, flexibly dosed from 40 to 160 mg/day, for 8 weeks.
Other Names:
  • Geodon
PLACEBO_COMPARATOR: Placebo Capsules
Identical placebo capsules will be dosed on a BID basis, with flexible dosing based on tolerability, with a total daily dose in the range of 40 to 160 mg/day.
Drug: Placebo
Placebo administered daily for 8 weeks
Other Names:
  • Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hamilton Anxiety Rating Scale (HAM-A)
Time Frame: 8 weeks

The 14-item Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1959) was developed to assess anxiety in a clinical population. It is considered a measure of general anxiety across anxiety disorders, in addition to being a gold standard measure for GAD.

Due to study termination, there are not results for primary and secondary outcome measures.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression of Improvement (CGI-I)
Time Frame: 8 weeks

A secondary categorical outcome of response will be defined as a Clinical Global Impression Improvement Score (CGI-I) of 1 or 2. The CGI-I is a 7 point clinician-rated scale that assesses symptom improvement or worsening relative to a previous assessment. Lower ratings reflect greater improvement.

Due to study termination, there are not results for primary and secondary outcome measures.
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Pfizer

Investigators

  • Principal Investigator: Naomi M. Simon, M.D., Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (ACTUAL)

October 1, 2007

Study Completion (ACTUAL)

November 1, 2008

Study Registration Dates

First Submitted

September 8, 2006

First Submitted That Met QC Criteria

September 8, 2006

First Posted (ESTIMATE)

September 11, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

April 16, 2014

Last Update Submitted That Met QC Criteria

March 20, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006-P-000142

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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