Ziprasidone in Bipolar Disorder With Comorbid Lifetime Panic or Generalized Anxiety Disorder(GAD)

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.

Inclusion Criteria:

- Subjects must at least age of 18 years of age and not older than 65.

- 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 generalized anxiety disorder 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 including hepatic, renal, respiratory,
cardiovascular, endocrine, neurological, or hematological disease 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 patient's
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