Bipolar DisorderPhase 2/3NCT00562861
Treatment for Bipolar Depression: Acute & Prophylactic Efficacy With Citalopram
A Phase 2/3 study testing citalopram + mood stabilizer in people with Bipolar Disorder and Bipolar Depression, run by Tufts Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Bipolar Disorder, Bipolar Depression
- What is being tested?
- citalopram + mood stabilizer
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 119 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Jul 2014
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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.
- Conditions
- Bipolar Disorder, Bipolar Depression
- Being tested
- citalopram + mood stabilizer, placebo + mood stabilizer
- Keywords
- Bipolar Disorder, Bipolar Depression, Clinical Trials, Phase II, Clinical Pharmacology
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
citalopram + mood stabilizerDrug
Also called Celexa
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.
placebo + mood stabilizerDrug
Also called lithium, lamotrigine, valproate, or carbamazepine
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.
| Study group | Role | What they receive |
|---|---|---|
| citalopram + mood stabilizer | Active comparator | All patients are on baseline mood stabilizers and are randomized to receive citalopram or placebo. In this arm, they are randomly assigned to citalopram. Receives: Drug: citalopram + mood stabilizer |
| placebo + mood stabilizer | Placebo comparator | All patients are on baseline mood stabilizers and are randomized to receive citalopram or placebo. In this arm, they are randomly assigned to placebo Receives: Drug: placebo + mood stabilizer |
What is being measured
The primary outcome is the main question the study is designed to answer.
MADRS Rating Scale Change
Montgomery Asberg Depression Rating scale assessed in mixed effects regression model. The total range for the scale is 0 to 60. Lower values involve less depression, while higher values involve worse depression. The change in the MADRS scale is interpreted as higher values meaning better outcomes, because more depressive symptoms are improved.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2007 (estimated)
- Study startNov 2007
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Nassir Ghaemi, MD, MPH, Principal investigator, Tufts University Medical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00562861
- Sponsor's protocol ID
- MH78060-01A1
- Other IDs
- 5R01MH078060-04
- Status last verified
- Feb 2017
- First submitted
- 20 Nov 2007
- Last updated
- 24 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ghaemi SN, Whitham EA, Vohringer PA, Barroilhet SA, Amerio A, Sverdlov O, Patkar AA. Citalopram for Acute and Preventive Efficacy in Bipolar Depression (CAPE-BD): A Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Psychiatry. 2021 Jan 12;82(1):19m13136. doi: 10.4088/JCP.19m13136.
PubMed 33434956
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment for Bipolar Depression: Acute & Prophylactic Efficacy With Citalopram
- ClinicalTrials.gov ID
- NCT00562861
- Acronym / sponsor ID
- MH78060-01A1
- Conditions
- Bipolar Disorder, Bipolar Depression
- Keywords
- Bipolar Disorder, Bipolar Depression, Clinical Trials, Phase II, Clinical Pharmacology
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Nov 2007
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 22 Nov 2007 (estimated)
- Results
- Posted 13 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| citalopram + mood stabilizer | Active comparator | Drug: citalopram + mood stabilizerAll patients are on baseline mood stabilizers and are randomized to receive citalopram or placebo. In this arm, they are randomly assigned to citalopram. |
| placebo + mood stabilizer | Placebo comparator | Drug: placebo + mood stabilizerAll patients are on baseline mood stabilizers and are randomized to receive citalopram or placebo. In this arm, they are randomly assigned to placebo |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| citalopram + mood stabilizerAlso: CelexaCitalopram 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. | Drug | citalopram + mood stabilizer |
| placebo + mood stabilizerAlso: lithium, lamotrigine, valproate, or carbamazepineThis 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. | Drug | placebo + mood stabilizer |
Primary outcome
MADRS Rating Scale Change
Time frame: 6 weeks
Montgomery Asberg Depression Rating scale assessed in mixed effects regression model. The total range for the scale is 0 to 60. Lower values involve less depression, while higher values involve worse depression. The change in the MADRS scale is interpreted as higher values meaning better outcomes, because more depressive symptoms are improved.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33434956Ghaemi SN, Whitham EA, Vohringer PA, Barroilhet SA, Amerio A, Sverdlov O, Patkar AA. Citalopram for Acute and Preventive Efficacy in Bipolar Depression (CAPE-BD): A Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Psychiatry. 2021 Jan 12;82(1):19m13136. doi: 10.4088/JCP.19m13136.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nassir Ghaemi, MD, MPH principal investigator
Tufts University Medical
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing citalopram + mood stabilizer in people with Bipolar Disorder and Bipolar Depression, run by Tufts Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MADRS Rating Scale Change (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00562861, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2017.