Treatment for Bipolar Depression: Acute & Prophylactic Efficacy With Citalopram - Full Text View

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 II Phase III

MedlinePlus related topics:

Antidepressants Bipolar Disorder Depression Nuclear Scans

ChemIDplus related topics:

Escitalopram Benzetimide Citalopram Citalopram hydrobromide Dexetimide Escitalopram oxalate Divalproex sodium Valproate Sodium Valproic acid Lamotrigine Carbamazepine Lithium carbonate Lithium citrate BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title:	Treatment for Bipolar Depression: Acute & Prophylactic Efficacy With Citalopram

Further study details as provided by Emory University:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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:	July 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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. 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. Procedure: Genotyping Subjects will be asked to provide a blood sample at the start of the study for the genotyping portion of the study. Procedure: Blood Draw Subjects will have their blood drawn at the Emory Medical Labs at the same time as their safety labs are performed.
2: Placebo Comparator 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. Procedure: Genotyping Subjects will be asked to provide a blood sample at the start of the study for the genotyping portion of the study. Procedure: Blood Draw Subjects will have their blood drawn at the Emory Medical Labs 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.

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Eligibility

Ages Eligible for Study:	18 Years to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562861

Locations


United States, Georgia
	Emory University School of Medicine: Wesley Woods Health Center
	Atlanta, Georgia, United States, 30322

United States, Massachusetts
	Tufts University
	Boston, Massachusetts, United States, 02111

Sponsors and Collaborators

Emory University

National Institute of Mental Health (NIMH)

Investigators


Principal Investigator:	Nassir Ghaemi, MD, MPH	Tufts University Medical

More Information

Responsible Party:	Tufts Medical Center ( Nassir Ghaemi )
Study ID Numbers:	MH78060-01A1, MH-0708060-01
First Received:	November 20, 2007
Last Updated:	July 15, 2008
ClinicalTrials.gov Identifier:	NCT00562861
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

Bipolar Disorder

Bipolar Depression

Clinical Trials, Phase II

Clinical Pharmacology

Study placed in the following topic categories:

Depression

Bipolar Disorder

Lithium Carbonate

Depressive Disorder

Citalopram

Valproic Acid

Serotonin

Behavioral Symptoms

Affective Disorders, Psychotic

Carbamazepine

Mental Disorders

Mood Disorders

Lamotrigine

Psychotic Disorders

Dexetimide

Lithium

Additional relevant MeSH terms:

Parasympatholytics

Neurotransmitter Agents

Neurotransmitter Uptake Inhibitors

Molecular Mechanisms of Pharmacological Action

Cholinergic Antagonists

Anti-Dyskinesia Agents

Physiological Effects of Drugs

Psychotropic Drugs

Antiparkinson Agents

Cholinergic Agents

Sensory System Agents

Therapeutic Uses

Analgesics

Antidepressive Agents, Second-Generation

Antidepressive Agents

Tranquilizing Agents

Central Nervous System Depressants

Antimanic Agents

Serotonin Uptake Inhibitors

Pharmacologic Actions

Muscarinic Antagonists

Serotonin Agents

Autonomic Agents

Analgesics, Non-Narcotic

Peripheral Nervous System Agents

Central Nervous System Agents

Anticonvulsants

ClinicalTrials.gov processed this record on September 05, 2008

Sponsors and Collaborators:	Emory University National Institute of Mental Health (NIMH)
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00562861