| Conditions: |
|
Bipolar Disorder - Bipolar Depression |
| 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.
|
| Study Summary: |
|
The problem of interest
Depression is a common serious illness, with great personal suffering and a 10% or more risk
of suicide. There are two kinds of depression, bipolar (depression alternating with mood
swings) and unipolar ("simple" depression, or major depressive disorder). In both kinds of
depression, antidepressants are commonly used. However, unlike unipolar depression, where a
good deal of research supports this use, there is very little research on antidepressant use
in bipolar disorder. Some studies support benefit with antidepressants for bipolar
depression; i.e., if one is depressed, antidepressants can help a patient get better in the
short-term. However, long-term studies are limited; the few available studies with older
antidepressants did not demonstrate long-term preventive benefit. Some clinicians think new
generation antidepressants (like Prozac and other serotonin reuptake inhibitors) are safer
and more effective than the older antidepressants. Yet there are no rigorous long-term
studies of new generation antidepressants in bipolar disorder. Recent observational studies
with new antidepressants suggest that they may be harmful to some patients with bipolar
disorder.
Clinicians are thus left in a quandary. Antidepressants appear to be effective in the short
term, but should the antidepressants (especially new generation antidepressants) be
continued long-term? Some studies support both approaches. Importantly, some evidence
exists that antidepressants can make many patients worse, with more and more depression or
mania over time.
This is a major public health problem, since clinicians prescribe antidepressants for the
long-term in up to 80% of patients with bipolar disorder. This represents standard
treatment, despite the limitations of the available evidence and the suggestion that in some
patients such antidepressant use may be harmful.
This study is also looking at possible biological predictors that may reflect an individual
patients' likelihood that he or she will respond to a specific treatment.
How the problem will be studied
This project is one of the most rigorous studies of new generation antidepressants in
long-term treatment of bipolar disorder. We will recruit patients with bipolar disorder who
are currently in a depressive episode and are taking or eligible and interested in taking a
mood stabilizer such as lithium. Subjects will then be randomly put into one of two groups.
The first group will receive the generic antidepressant, citalopram while the other group
will receive placebo, sugar pill. Patients will be closely followed and monitored by the
research psychiatrist and through a series of safety labs. Subjects will have an MRI and PET
scan for the biological predictors section of the study. The key question is: After the
acute recovery, should they continue antidepressants or not?
As there is limited scientific data, and opposing kinds of clinical experience, there is no
clear rationale to making this decision. Our study seeks to provide a scientific basis for
making that decision. We plan to follow subjects for a goal of 1 year to obtain long-term
outcome data on which approach is best.
How the research will advance scientific knowledge or human health
Since there are no rigorous long-term studies with new generation antidepressants in bipolar
disorder, this study will be a major advance in that knowledge. Clinicians will have some
evidence on which to base that decision, rather than simply their own opinions or patients'
preferences. In the light of recent evidence that antidepressants are potentially harmful to
some patients, this study will provide more information about how new antidepressants work
specifically for bipolar patients rather than unipolar depression (also known as major
depression). The biological portion of the study will shed light on possible biological
factors that could show how an individual may respond to a specific treatment. This could
potentially help doctors to decide on which treatments are more or less likely to work for
their individual patients rather then using a "hit or miss" type method.
|
| 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
|
| NCT ID: |
|
NCT00562861 |
| Primary Contact: |
|
Principal Investigator
Nassir Ghaemi, MD, MPH
Tufts University Medical
Nassir Ghaemi, MD, MPH
Phone: 617-636-5735
Email: nghaemi@tuftsmedicalcenter.org
|
| Backup Contact: |
|
N/A |
| Location Contact: |
|
Boston, Massachusetts 02111
United States
Nassir Ghaemi, MD, MPH
Phone: 617-636-5735
Email: nghaemi@tuftsmedicalcenter.org
Site Status: Recruiting |