Pathophysiology and Treatment of Bipolar Disorder as Assessed by in Vivo Imaging
Overview
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Stony Brook University
- Enrollment
- 76
- Locations
- 1
- Primary Endpoint
- Prediction of Treatment Response
Overview
Brief Summary
The primary aims of this study are to:
- Quantify serotonin transporter (5-HTT) binding potential (BP) in vivo in bipolar disorder patients (BPD) during a major depressive episode (MDE).
- Assess the effect of lithium treatment of bipolar disorder on 5-HTT.
- Assess the effect of lithium treatment of bipolar disorder on 5-HT1A BP.
- Assess the effect of lamotrigine treatment of bipolar disorder on 5-HTT and 5-HT1A BP.
- Assess the effect of lithium treatment of unipolar depression on 5-HTT BP.
Detailed Description
PET and MRI imaging will be used to investigate the aims described above in patients who have bipolar disorder or unipolar depression and are currently experiencing a depressive episode. Both healthy controls and depressed participants with bipolar disorder or unipolar depression will be recruited. Patients who are on medication before enrolling in the study will have a three week washout. At baseline, healthy controls and patients will have an MRI consisting of both structural and functional sequences. Psychological measures will also be obtained at baseline. Within one week of the MRI, both patients and healthy controls will have one CUMI and one DASB PET scan.
Following the baseline PET scans, patient participants will begin medication treatment with either lithium or lamotrigine, based on the clinical judgement of the treating psychiatrist. Psychological measures will be obtained every 2 weeks. After 6 weeks of medication treatment at a therapeutic dose, patients will be assessed for remission (defined as a 50% decrease in the HDRS score from baseline). If this criteria is met, patient participants will then have follow-up PET scans (one CUMI and one DASB). If this criteria is not met, the patient will be switched to the other medication under study and will be reevaluated after an additional 4 weeks of medication treatment. Patients who still do not demonstrate a 50% decrease in their HDRS will be considered non-responders and will have repeat CUMI and DASB scans.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Bipolar patients suffering from a major depressive episode currently or recently (in the month prior to scanning). Patients on psychiatric medication will have failed their current regimen for the treatment of their depression: they will meet criteria for depression, be seeking treatment for it, and have been on an adequate dose of antidepressant or mood stabilizer (as defined by the Antidepressant Treatment Form-see Oquendo et al., 2003) for 4 weeks or more.
- •Of sufficient severity to score at least 15 on the first 17 items of the Hamilton Depression Rating Scale or a score of 10 to 14 on the first 17 items of the Hamilton Depression Scale in conjunction with a score of at least 29 on the Beck Depression Inventory.
- •Age range 18-65 years.
- •Off all psychotropic and other types of drugs likely to interact with serotonin transporters and 5-HT1A receptors for at least 21 days. Allowed short-acting benzodiazepines for distressing anxiety or insomnia (up to 24 hours prior to each PET scan). Patients will be off neuroleptics for 3 weeks and off fluoxetine for 6 weeks prior to study. Off serotonin depleting drugs such as reserpine for 3 months. Patient will also be off anti-coagulant/anti-platelet treatment such as coumadin, with the exception of aspirin for 10 days.
- •Willing to travel for PET scanning
Exclusion Criteria
- •Other major psychiatric disorders such as schizophrenia, schizoaffective illness; current drug or alcohol abuse (within past 2 months), or drug or alcohol dependence \<6mos ago; anorexia nervosa or bulimia nervosa in the past year; IV drug use or ecstasy use more than two times.
- •A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations).
- •Significant active physical illness particularly those that may affect the brain or serotonergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, diabetes, low hemoglobin and malignancy, significant anemic disease or blood loss and the lab parameters platelet count \< 80,
- •Lacks capacity to consent.
- •Actively suicidal-begins expressing a plan for suicide during the washout phase or develop suicidal ideation that warrants admission or requires medication or treatment intervention.
- •Electroconvulsive therapy (ECT) within the past 6 months.
- •Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.
- •Metal implants, pacemaker or metal prostheses or orthodontic appliances, the presence of shrapnel
- •Current, past or anticipated exposure to radiation, that may include: being badged for radiation exposure in the workplace, participation in nuclear medicine procedures, including research protocols in the last year.
- •A neurological disease or loss of consciousness for more than a few minutes
Arms & Interventions
Lithium
Patients in this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode
Intervention: Lithium (Drug)
Lamotrigine
Patients who have not respond to adequate prior lithium treatment while depressed, or who refuse lithium, will be given lamotrigine. Lamotrigine will be started at 25 mg bid and increased to 50 mg bid after 2 weeks and again increased to 100 mg bid after an additional 2 weeks.
Intervention: Lamotrigine (Drug)
Outcomes
Primary Outcomes
Prediction of Treatment Response
Time Frame: 8 Weeks
Outcome measures were generated following LASSO linear regression analysis using pretreament HDRS-24 AND.. 1. pre-treatment 5-HTT OR 2. pretreatment 5-HT1A OR 3. the combination of both 5-HTT and 5-HT1A binding potential * to predict post-treatment response defined by a dichotomous remission status variable (remitter vs. non-remitter, where remitter is defined a priori by HDRS-24 \<10 post-treatment and a reduction of greater than or equal to 50% in HDRS-24 pre-to-post treatment). Outcome measure is reported as percent accuracy, sensitivity, or specificity in predicting remitter status outcomes.
Post-Lithium Treatment Hamilton Depression Rating Scale (HDRS)
Time Frame: 8 weeks
Patients will have a Hamilton Depression Rating Scale-24 (HDRS) score obtained at baseline. Minimum score 0, maximum possible score 75; the higher the score on the scale, the more severe the degree of depression. Participants must have an HDRS score of at least 15 to be eligible. After eight weeks of medication treatment, the HDRS score will be reevaluated with the HDRS-24 (and rescanned with PET and MRI). Participants who have a 50% or greater decrease in their HDRS-24 score will be considered responders (to Lithium treatment).
Secondary Outcomes
- Group Differences in 5-HTT Binding Potential(8 Weeks)
- Group Differences in 5-HT1A Binding Potential(8 Weeks)
- Relationship Between Change in 5-HTT or 5-HT1A Binding Potential Pre- to Post Treatment and Lithium Treatment Response(8 weeks)
Investigators
Ramin Parsey
Professor and Chair of the Department of Psychiatry and Director of Positron Emission Tomography (PET) Research
Stony Brook University