Treatment for Bipolar Depression: Acute & Prophylactic Efficacy With Citalopram
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Purpose
Bipolar depression is one of the least studied depressive illnesses. The standard practice for many doctors is to use antidepressant medicines, but there are few studies on the long-term results of these medicines. The goal of this study is to look at how effective and safe these medicines are in treating bipolar depression when taken with a mood stabilizer medicine.
The drug being studied is citalopram, also known as Celexa. Celexa is FDA approved for the treatment of major depression, but is not FDA approved for the treatment of bipolar depression. It is, however, standard practice for many doctors is to use antidepressants, like Celexa, to treat their patients with bipolar disorder depression.
The drug will be studied in three ways. We will see if it helps treat depressive symptoms. We will see how the drug affects the brain using PET and fMRI scans. Finally, we will look at the possibility that there may be a gene that could predict if a person would get better taking the drug using genetics.
| Condition | Intervention | Phase |
|---|---|---|
|
Bipolar Disorder Bipolar Depression |
Drug: citalopram + mood stabilizer Procedure: FDG PET scans Procedure: MRI structural scans Procedure: Genotyping Procedure: Blood Draw Drug: placebo + mood stabilizer |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Treatment for Bipolar Depression: Acute & Prophylactic Efficacy With Citalopram |
- In acute treatment, citalopram will be more effective than placebo for depressive symptoms in bipolar disorder [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- In acute treatment, citalopram will be associated with a greater risk of acute hypomania, mixed-states, or mania than placebo. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- In maintenance treatment, the total number of affective episodes and their rate (episodes/study time), as well as time to intervention with other medications and time to first episode, will be lower in the placebo than in the citalopram group. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Antidepressant response or remission in depressed bipolar patients will be associated with changes in cortical and paralimbic regions, consistent with SRI antidepressant response in unipolar depressed patients. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
- Polymorphic variation at the 5HTTLPR gene will alter the risk of acute mania or increased mood-cycling with citalopram vs. placebo treatments [ Time Frame: 1 year ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 150 |
| Study Start Date: | November 2007 |
| Estimated Study Completion Date: | May 2013 |
| Estimated Primary Completion Date: | May 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
Mood stabilizer plus citalopram
|
Drug: citalopram + mood stabilizer
Citalopram dose will be flexibly designed, beginning at 10 mg/d for at least one week, and the increased by 10 mg per week to a maximum of 50 mg/d. No target dose will be provided but rather clinicians will dose to clinical efficacy. Thus the study will provide clinicians data on the effective dose if it is positive. The dose will not be predetermined at static amounts.
Other Name: Celexa
Procedure: FDG PET scans
Two scans will be acquired in two separate PET imaging sessions, 6 weeks apart (baseline vs. end-of-acute treatment phase). The exploratory imaging component of this study will be limited to 60 individuals (30 in each arm) taking lithium as a sole mood stabilizer.
Procedure: MRI structural scans
MRI acquisitions will be acquired using a Siemens 3T whole body scanner (Trio) with a 60 cm diameter bore. Anatomical imaging will be conducted for anatomic reference for precise spatial normalization of co-registered PET images for the planned functional analyses. The exploratory imaging component of this study will be limited to 60 individuals (30 in each arm) taking lithium as a sole mood stabilizer. Subjects will be asked to provide a blood sample at the start of the study and after 6 weeks for the genotyping portion of the study.
Procedure: Blood Draw
Subjects will have their blood drawn at Tufts Medical Center at the same time as their safety labs are performed.
|
|
Placebo Comparator: 2
Mood stabilizer alone
|
Procedure: FDG PET scans
Two scans will be acquired in two separate PET imaging sessions, 6 weeks apart (baseline vs. end-of-acute treatment phase). The exploratory imaging component of this study will be limited to 60 individuals (30 in each arm) taking lithium as a sole mood stabilizer.
Procedure: MRI structural scans
MRI acquisitions will be acquired using a Siemens 3T whole body scanner (Trio) with a 60 cm diameter bore. Anatomical imaging will be conducted for anatomic reference for precise spatial normalization of co-registered PET images for the planned functional analyses. The exploratory imaging component of this study will be limited to 60 individuals (30 in each arm) taking lithium as a sole mood stabilizer. Subjects will be asked to provide a blood sample at the start of the study and after 6 weeks for the genotyping portion of the study.
Procedure: Blood Draw
Subjects will have their blood drawn at Tufts Medical Center at the same time as their safety labs are performed.
Drug: placebo + mood stabilizer
This arm will only receive mood stabilizing medication. All subjects will be required to receive treatment with lithium, lamotrigine, valproate, or carbamazepine for at least one month at therapeutic blood levels or doses before randomization, or they must initiate one of these agents at study entry.
Other Name: lithium, lamotrigine, valproate, or carbamazepine
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years to 64 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Current age ≥18 years
- DSM-IV diagnosis of BPD, type-I, or type-II
- Current major depressive episode using DSM-IV criteria, lasting 8 weeks or longer.
- Use of lithium, divalproex, carbamazepine, or lamotrigine at therapeutic serum levels or doses for ≥4 weeks prior to study entry, or willingness to accept one of these agents.
- Prior to initial evaluations, each subject must provide competent, written, informed consent.
Exclusion Criteria:
- Past non-response to a therapeutic trial of R,S-citalopram (≥100 mg/day for ≥8 weeks).
- Previous intolerance of R,S-citalopram;
- Diagnosis of unipolar depression
- Diagnosis of schizoaffective disorder
- Serious medical illness with acute instability (cardiac, respiratory, hepatic, renal), based on hospitalization in the past month
- Abnormal thyroid function tests
- Previous allergic reaction to or inability to tolerate lithium, divalproex, or carbamazepine at therapeutic serum levels.
- Current or past renal dysfunction if taking lithium
- Current or past hepatitis or other liver disease if taking divalproex
- Current or past hematologic disease if on carbamazepine
- Severe suicidal ideation, plan or intent, as documented by a score of ≥4 on the Montgomery Åsberg Depression Rating Scale suicidality item (Item 10).
- Presence of psychosis
- Cognitive impairment sufficient to impair ability to give informed consent.
- Current pregnancy, or inability to utilize contraception
- The presence of any metallic implants
- History of claustrophobia
Contacts and Locations| Contact: Nassir Ghaemi, MD, MPH | 617-636-5735 | nghaemi@tuftsmedicalcenter.org |
| United States, Georgia | |
| Emory University School of Medicine: Wesley Woods Health Center | Suspended |
| Atlanta, Georgia, United States, 30322 | |
| United States, Massachusetts | |
| Tufts Medical Center | Recruiting |
| Boston, Massachusetts, United States, 02111 | |
| Contact: Nassir Ghaemi, MD, MPH 617-636-5735 nghaemi@tuftsmedicalcenter.org | |
| Principal Investigator: Nassir Ghaemi, MD, MPH | |
| United States, North Carolina | |
| Duke University School of Medicine | Not yet recruiting |
| Durham, North Carolina, United States, 27705 | |
| Contact: Josephine White- Harper 919-681-0613 | |
| Principal Investigator: Ashwin Patkar, MD | |
| Principal Investigator: | Nassir Ghaemi, MD, MPH | Tufts University Medical |
More Information
No publications provided
| Responsible Party: | Nassir Ghaemi, Director of Mood Disorders Program, Tufts Medical Center |
| ClinicalTrials.gov Identifier: | NCT00562861 History of Changes |
| Other Study ID Numbers: | MH78060-01A1, MH-0708060-01 |
| Study First Received: | November 20, 2007 |
| Last Updated: | December 10, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Tufts Medical Center:
|
Bipolar Disorder Bipolar Depression Clinical Trials, Phase II Clinical Pharmacology |
Additional relevant MeSH terms:
|
Bipolar Disorder Depression Depressive Disorder Affective Disorders, Psychotic Mood Disorders Mental Disorders Behavioral Symptoms Citalopram Dexetimide Valproic Acid Carbamazepine Lithium Lamotrigine Antidepressive Agents, Second-Generation Antidepressive Agents |
Psychotropic Drugs Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Serotonin Agents Physiological Effects of Drugs Antiparkinson Agents Anti-Dyskinesia Agents Parasympatholytics Autonomic Agents Peripheral Nervous System Agents |
ClinicalTrials.gov processed this record on May 23, 2013