Prediction of Clinical Response to SSRI Treatment in Bipolar Disorder Using Serotonin 1A Receptor PET Imaging
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Intervention: Fluoxetine; Citalopram
Intervention description: Bipolar depressed patients will be treated with fluoxetine in combination with a mood stabilizer (valproate).; Bipolar depressed patients will be treated with citalopram in combination with a mood stabilizer (valproate) if fluoxetine is not clinically warranted.
Intervention MeSH terms: Fluoxetine; Citalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      This study is for subjects with a diagnosis of bipolar disorder who have depression at the
      time of recruitment. It involves brain imaging with an MRI (magnetic resonance imaging) and
      PET scan (positron emission tomography) and treatment with an antidepressant. The medication
      involves adding an SSRI (either celexa/citalopram or prozac/fluoxetine) to a mood stabilizer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to provide informed consent

          -  Diagnosis of bipolar I disorder or bipolar II disorder and currently meet criteria for
             a major depressive episode

          -  Patients who were on psychiatric medication at presentation will have failed that
             regimen, as defined as not achieving at least partial remission after an adequate dose
             of medication for at least six weeks.

          -  Depression of sufficient severity to score at least 16 on the first 17 items of the
             Hamilton Depression Rating Scale

          -  Age range 18-60 years

          -  Females of child-bearing potential must be willing to use an acceptable method of
             birth control throughout the study.

          -  Subject agrees to discontinue all psychotropic other than those in the PSF and other
             types of drugs likely to interact with the 5-HT1A receptors.

          -  Subject is likely to tolerate medication cross-taper to monotherapy with a mood
             stabilizer (valproate, lamotrigine or lithium).

        Exclusion Criteria:

          -  Diagnosis of any other major psychiatric disorders such as lifetime schizophrenia,
             schizoaffective disorder, current psychotic depression or current drug or alcohol
             abuse (within two months before the study) or recent drug or alcohol dependence
             (within six months before the study); anorexia nervosa or bulimia nervosa within the
             last year; IV drug use of ecstasy use more than three times. Meet criteria for a manic
             episode at the time of screening.

          -  Previous failed trial of fluoxetine and citalopram by themselves or in combination
             with an anti-manic agent, defined as at least six weeks of treatment at the dose of 20
             mg per day or more. Failure of two trials of any SSRI or SNRI antidepressant
             medications.

          -  If the patients are discontinuing medications as part of the washout period or are
             starting valproate, previous failed trial of mood stabilizer that they will take
             alone.

          -  Experienced intolerable side effects of both citalopram and fluoxetine in the past. If
             the subject is not on medications, intolerable side effects of valproate in the past.

          -  History of clinical deterioration when any of the medications that the patient is
             taking at presentation have been discontinued in the past with the exception of any
             medications that will be continued during the research protocol.

          -  A first-degree family history of schizophrenia if the subject is less than 33 years
             old

          -  Significant active physical illness, including blood dyscrasias, lymphomas,
             hypersplenism, endocrinopathies, renal failure, chronic obstructive lung disease,
             autonomic neuropathies, peripheral vascular disease, malignancy

          -  Actively suicidal, as defined by expressing ideation with a plan for suicide or
             develops suicidal ideation that requires immediate medication or treatment
             intervention.

          -  Pregnancy, abortion or miscarriage in the two months prior to enrollment or plans to
             conceive during the course of study participation

          -  Lactating women

          -  ECT within the past 6 months

          -  Subjects who endorse a history of prior head trauma and score 1.5 standard deviations
             below the mean on Trail-making A & B will be excluded from study participation.

          -  Metal implants, pacemaker, metal prostheses, metal orthodontic appliances or shrapnel
             in the body

          -  Current, past or anticipated exposure to radiation, including:

               -  Having been badged for radiation exposure in the workplace

               -  Participation in nuclear medicine protocols in the last year. Subjects will be
                  eligible, however, if the injected dose and dosimetry of the radiotracer are
                  known and the cumulative annual exposure of the previous study and this study is
                  lower than the annual limit for research subjects defined by the FDA (21 CFR
                  361.1)

          -  History of claustrophobia that would prevent the participation in imaging scans

          -  Current anticoagulant or anti-platelet treatment other than aspirin

          -  Obesity with weight >350 lbs or inability to fit into the MRI scanner