A Randomized, Double-Blind, Placebo-Controlled Study of Ziprasidone in Bipolar Disorder With Comorbid Lifetime Panic or Generalized Anxiety Disorder
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 49
- Locations
- 3
- Primary Endpoint
- Clinician Global Improvement Scale (CGI-21)
Study Overview
Brief Summary
The specific aim of this study is to evaluate the efficacy, tolerability, and safety of ziprasidone monotherapy in comparison to placebo in the treatment of ambulatory bipolar disorder with co-morbid lifetime panic disorder or generalized anxiety disorder and current at least moderately severe anxiety.
Detailed Description
This is a randomized, double-blind, placebo controlled, parallel-group, 8-week trial of ziprasidone compared to placebo in outpatient subjects with a lifetime bipolar I, II, or NOS disorder, a lifetime panic or generalized anxiety disorder, and current diagnosis at least moderately severe anxiety symptoms. Approximately 50 subjects will be randomized. Subjects will be randomized to ziprasidone or placebo in a 1:1 ratio. No concomitant psychotropic medication will be allowed throughout the study except for prn lorazepam during the first two weeks for the management of affective and anxiety symptoms, prn zolpidem and zaleplon for the management of insomnia and benztropine for the management of EPS. Throughout the study, psychiatric scales will be used to assess psychiatric symptoms and the presence of treatment-emergent adverse events will be monitored and recorded.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subjects must be at least 18 and not older than
- •Subjects must have lifetime bipolar I, II, or NOS disorder as defined by DSM-IV TR criteria (26).
- •Subjects must have lifetime panic disorder or generalized anxiety disorder (GAD) as defined by DSM-IV criteria (except clause "does not occur exclusively during a mood disorder" of Criterion F for GAD).
- •Subjects' bipolar symptoms must be no more than moderate in severity, defined as a CGI-BP< 4 (27).
- •Subjects' anxiety symptoms must be at least moderate in severity, defined as a CGI-S > 4 (28).
- •Subjects must not be receiving regular mood stabilizing, antidepressant, antipsychotic, or anxiolytic medication for at least one week prior to baseline. Patients receiving fluoxetine or depot antipsychotics should be off these medications for at least four weeks prior to baseline.
- •Subjects or their legally authorized representative must sign the Informed Consent Document after the nature of the trial has been fully explained.
- •If female, subjects must be: postmenopausal, surgically incapable of childbearing, or practicing medically acceptable effective method(s) of contraception (e.g., hormonal methods, barrier methods, intrauterine device) for at least one month prior to study entry and throughout the study.
Exclusion Criteria
- •Subjects who do not have lifetime bipolar disorder by DSM-IV-TR criteria (26).
- •Subjects who do not have lifetime panic disorder or GAD by DSM-IV-TR criteria (26).
- •Subjects who are receiving treatment with an anti-manic or mood stabilizing medication (lithium, valproate, carbamazepine, or an antipsychotic), and in the investigators' judgment, require ongoing treatment with that medication.
- •Subjects whose bipolar symptoms are presently more than moderately severe (CGI-BP > 5) (27).
- •Subjects whose anxiety symptoms are presently less than moderately severe (CGI-S < 3) (28).
- •Subjects with clinically significant suicidal or homicidal ideation.
- •Subjects with a current DSM-IV TR Axis I diagnosis of delirium, dementia, amnesia, or other cognitive disorders; a DSM-IV TR diagnosis of a substance dependence disorder within the past six months; a lifetime DSM-IV TR psychotic disorder (e.g., schizophrenia or schizoaffective disorder).
- •Subjects with serious general medical illnesses as determined by the clinical judgment of the clinical investigator. Subjects with hypo- or hyperthyroidism unless stabilized on thyroid replacement > 3 months.
- •Subjects with a clinically significant abnormality in their pre-study physical exam, vital signs, EKG, or laboratory tests.
- •Subjects who are allergic to or who have demonstrated hypersensitivity or intolerance to ziprasidone.
- •Women who are pregnant or nursing.
- •Subjects who have received an experimental drug or used an experimental device within 30 days.
- •Subjects who have a history of neuroleptic malignant syndrome.
- •A patient with diabetes mellitus (DM) fulfilling one of the following criteria:
- •Unstable DM defined as enrollment glycosylated hemoglobin (HbAlc) >8.5%
- •Admitted to hospital for treatment of DM or DM related illness within the past 12 weeks
- •Not under physician care for DM
- •Physician responsible for patient's DM care has not indicated that the DM is controlled
- •Physician responsible for patient's DM care has not approved the patient's participation in the study
- •Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the 4 weeks before randomization. For thiazolidinediones(glitazones)this period should not be less than 8 weeks before randomization.
- •Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks
- •Note: If a patient with DM meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study
Arms & Interventions
Placebo
Administered in capsules identical to the ziprasidone capsules.
Intervention: Placebo (Drug)
ziprasidone
Ziprasidone in the form of 40 and/or 80 mg capsules. Dose range: 40 to 160 mg/day.
Intervention: Ziprasidone (Drug)
Outcomes
Primary Outcomes
Clinician Global Improvement Scale (CGI-21)
Time Frame: 8 weeks
CGI-21 Anxiety Scale ranges from -10 (Very Bad. Could not be worse) to +10 (Major Improvement. Back to normal self).
Secondary Outcomes
- Hamilton Anxiety Rating Scale (HAM-A)(8 weeks)
- Young Mania Rating Scale(8 weeks)
- Montgomery-Asberg Depression Rating Scale (MADRS)(8 weeks)
- CGI-BP(8 weeks)
- Sheehan Disability Scale (SDS)(8 weeks)
- Sheehan Irritability Scale (SIS)(8 Weeks)
Investigators
patricia suppes
Director, Bipolar and Depression Research Program
VA Palo Alto Health Care System