Bipolar Disorder, Generalized Anxiety Disorder
Conditions
Keywords
Bipolar Disorder, Generalized Anxiety Disorder, Double-blind, Placebo-controlled, Ziprasidone
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: 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.
Interventions
DRUGZiprasidone
Ziprasidone, flexibly dosed from 40 to 160 mg/day, for 8 weeks.
DRUGPlacebo
Placebo administered daily for 8 weeks
Sponsors
Pfizer
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Rating Scale (HAM-A) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Improvement (CGI-I) | 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. |
Countries
United States
Participant flow
Recruitment details
Numerous attempts were made to increase enrollment since study inception. Researchers made use of Radio, Internet and print ads, as well as weekly Internet postings. Researchers also circulated an IRB-approved GAD checklist in a Bipolar Clinic waiting area in order to increase enrollment and recruit a clinically relevant sample.
Pre-assignment details
A total of thirteen individuals signed consent, but only three were randomized to the study arms. The other ten participants were excluded from the study for meeting various exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone, 40 to 160 mg/Day Patients with Bipolar Disorder and Anxiety Comorbidity who consent and meet entry criteria will be randomized to placebo or Ziprasidone. Ziprasidone 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. | 2 |
| Placebo Patients with Bipolar Disorder and Anxiety Comorbidity who consent and meet entry criteria will be randomized to placebo or Ziprasidone. 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. | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Ziprasidone, 40 to 160 mg/Day | Placebo | Total |
|---|---|---|---|
| Age, Customized >= 18 to 75 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Customized <18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >75 years | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
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.
Time frame: 8 weeks
Population: Zero participants were analyzed because recruitment was very low. Due to this, we felt any analysis done would not be usable for accurate analyses.
Secondary
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.
Time frame: 8 weeks