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

Study Overview
=================
Brief Summary
-----------------
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.

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: 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). 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. Treatment with ziprasidone will have a significantly greater positive impact on measures of quality of life and resilience than placebo.

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

Conditions
-----------------
Generalized Anxiety Disorder, Bipolar Disorder

Intervention / Treatment
-----------------
* Drug: Ziprasidone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ziprasidone<br>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<br>* Ziprasidone, flexibly dosed from 40 to 160 mg/day, for 8 weeks.<br>* Other names: Geodon;|
| Placebo Comparator: Placebo Capsules<br>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<br>* Placebo administered daily for 8 weeks<br>* Other names: Control;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Anxiety Rating Scale (HAM-A) | 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) | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bipolar Disorder, Generalized Anxiety Disorder, Double-blind, Placebo-controlled, Ziprasidone