Bipolar DisorderPhase 4NCT00464191
Escitalopram in Bipolar Depression: a Placebo-controlled Study of Acute and Maintenance Treatment
A Phase 4 study testing escitalopram in people with Bipolar Disorder, run by Nordfjord Psychiatric Centre at 1 site in Norway.
Trial summary
Funding: An investigator-initiated trial funded by H. Lundbeck AS. Study design: Prospective, randomised, placebo-controlled parallel-group multicenter study. Aim: To investigate efficacy and side effects (especially mood switches) of escitalopram,a selective serotonin reuptake inhibitor, in the acute and maintenance… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- escitalopram
- How many people
- 150 participants
- Where
- 1 siteNorway
- Study dates
- Apr 2006to Mar 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with bipolar disorder in major depressive episode according to DSM-IV
- MADRS score of at least 20 points at screening and baseline
- 18-70 years of age
- Unchanged dose of mood stabilising medication for at least six weeks prior to inclusion
- Voluntary, informed and written consent
Who cannot join
- Non-affective psychotic symptoms at screening
- Pregnancy or breast-feeding
- Fertile women without appropriate contraception (the pill, IUD, or contraceptive injection)
- Substance dependence during the last three months prior to baseline
- Mental retardation and organic brain disorders
- Suicide risk that mandates specific measures
Show all 15Show fewer
- Novel (within three months) or unstable medical conditions
- Clinically significant abnormal results on medical examination or blood samples
- Exposure to escitalopram during the last three months
- Allergic reactions to citalopram or escitalopram
- Anorexia nervosa with body mass index below 18
- Formal psychotherapy started within six weeks of screening
- Electroconvulsive therapy (ECT) during the current episode of depression
- Patients who are unlikely to be reliable and compliant with study procedures
- Patients who are not fluent in Norwegian
Trial locations and contacts
1 site in 1 country.
About this study
Funding: An investigator-initiated trial funded by H. Lundbeck AS.
Study design: Prospective, randomised, placebo-controlled parallel-group multicenter study.
Read more
Aim: To investigate efficacy and side effects (especially mood switches) of escitalopram,a selective serotonin reuptake inhibitor, in the acute and maintenance treatment of bipolar depression.
Hypotheses:
- Escitalopram, given in addition to mood stabilising medications, is significantly more efficacious, measured by response and remission rates than placebo in bipolar depression (the acute phase study).
- Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
- The incidence of "mood switching" (defined as development of mixed episodes, mania, or hypomania according to DSM-IV criteria) do not differ significantly between escitalopram and placebo in either the acute or the continuation phases.
Patients: In- and outpatients receiving care in the specialised psychiatric services of Western Norway. The population is intended to be representative of the patients treated for bipolar depression in ordinary specialist care. Patients must have a MADRS score of at least 20 at baseline. Patients with ongoing substance abuse or dependence, organic mental illness, and non-affective psychotic symptoms are excluded.
Medication: Escitalopram 10-20 mg daily or placebo in addition to mood stabilisers. The dose of mood stabilisers must have been constant for the last six weeks prior to randomisation.
Method: Phase 1 is a eight-week acute treatment trial with six clinical assessments. Patients treated with escitalopram who have not responded after eight weeks (defined by at least 50% reduction of MADRS score compared to baseline) leave the study. Placebo non-responders are treated openly with escitalopram and repeat phase 1. Responders are re-randomised to 32 weeks of maintenance treatment (phase 2). Phase 2 has nine clinical assessments. Patients who develop hypomania, mania or depressive episodes (defined as episodes meeting DSM-IV criteria for Major Depressive Episode with MADRS scores of at least 20 points) leave the study in this phase. Patients leaving the study prematurely will be offered alternative treatment.
Read the detailed description
Aims
The study has two main aims:
- To compare the efficacy and the risk of "mood switching" of escitalopram and placebo in the acute phase treatment of bipolar depression in patients already taking mood stabilising medication.
- To compare the efficacy of escitalopram and placebo in continuation phase therapy for bipolar depression using a placebo-controlled discontinuation design. The study will compare the occurrence of syndromal and subsyndromal relapses, mixed states, mania, hypomania, and "rapid cycling" in a seven months' maintenance study following response to acute phase treatment.
Hypotheses
- Escitalopram, given in addition to mood stabilising medications, is significantly more efficacious, measured by response and remission rates than placebo in bipolar depression (the acute phase study).
- Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
- The incidence of "mood switching" (defined as development of mixed episodes, mania, or hypomania according to DSM-IV criteria do not differ significantly between escitalopram and placebo in either the acute or the continuation phases.
Design This is a multi-center RCT with parallel-group design. The study compares the efficacy of placebo and escitalopram, given as add-on to mood stabilising medications in patients with bipolar depression without non-affective psychotic symptoms according to DSM-IV, and with a baseline MADRS score of ≥ 20 points.
The study has two phases. The acute phase study lasts for eight weeks and compares the efficacy of escitalopram and placebo on depressive symptoms in bipolar depression. Response is defined as at least 50% improvement on the MADRS compared to the baseline score. Responders to escitalopram are re-randomised to escitalopram or placebo for the continuation phase while placebo responders continue taking placebo for the continuation phase. Patients on escitalopram who do not respond in the acute phase leave the study, whereas placebo non-responders are treated openly with escitalopram and repeat phase 1. Responders to this open-label treatment are then re-randomised double blind to escitalopram or placebo for the continuation study.
The continuation phase study lasts for 32 weeks. Patients who responded to placebo in the acute phase continue placebo and their usual mood stabilising medication for the remainder of the study. Those who responded to escitalopram are re-randomised to continue taking placebo or escitalopram in unchanged doses. Patients who develop new mood episodes (DSM-IV-defined major depressive episode, mania, hypomania, or mixed episodes) or MADRS score ≥ 20 points leave the study.
Method Screening includes sociodemographic variables, medical and psychiatric history, diagnosis made on the basis of clinical interview and verified by the MINI, symptom intensity measured by the MADRS,), results of medical examination and laboratory tests (ECG, height, weight, blood pressure and blood tests). Sociodemographic variables include age, gender, previous and concomitant disorders, course and treatment of mental disorders, bipolar disorder type (I or II), age of onset and history of psychotropic medication use.
Study procedure As soon as the blood samples are analysed, eligible patients can be randomised. They are rated on the MADRS, Clinical Global Impressions (CGI), Inventory of Depressive Symptoms - Self Report (IDS-SR), Medical Outcomes Study Short Form 12 (SF-12), Global Assessment of Functioning (GAF) and Sheehan Disability Inventory (SDI) at the baseline visit. Study medication is dispensed. The patients will return to further visits as shown below. Patients will receive study medication for a maximum of 40 weeks. Adverse events and concomitant medications are recorded.
Assessments
The following assessments will be carried out::
- MADRS, GAF, IDS-RS, and CGI-I at week 1, 2, 4, 6, 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
- SDI and QLDS at week 8 and 40
- Diagnostic criteria for Mania and Hypomania at week 1, 2, 4, 6, 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
- Diagnostic criteria for Major Depressive Episode at week 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
For the acute study, response and remission rates as assessed by the MADRS are the primary outcome measures. CGI-Improvement and IDS-SR are secondary outcome measures. In the continuation study, primary outcome measures include emergence of major depressive episodes and mania/hypomania, while time spent at different depressive symptom levels as assessed by the DSM-IV diagnostic criteria are secondary outcome measures.
Definitions Response: at least a 50% reduction of the baseline MADRS score at the end of phase 1 if the patient has completed at least four weeks of the study. CGI-I 1 or 2 at the end of phase 1.
Remission: MADRS score of 12 or less at the end of the acute phase if the patient has completed at least four weeks of the study.
New episode: A patient who has previously responded to treatment meets the DSM-IV criteria for Major Depressive Episode. The patient must score at least 15 points on the MADRS and have a CGI-S score of 3 or more during this episode.
Mania and hypomania: by DSM-IV criteria.
- Conditions
- Bipolar Disorder
- Being tested
- escitalopram
- Keywords
- bipolar depression, SSRI, escitalopram, bipolar disorder, antidepressant, treatment trial, RCT
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
escitalopramDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1:
response rates
remission rates
Phase 2:
emergence of major depressive episodes
emergence of mania, hypomania, and mixed states.
Secondary outcomes (5)
Phase 1:
CGI-Improvement
change on the IDS-SR
Phase 2:
Time spent at different depressive symptom levels as assessed by the DSM-IV diagnostic criteria.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2007 (estimated)
- Study startApr 2006
- Primary completionMar 2009
- Study completionMar 2009
Why it stopped: The study has been terminated because too few patients have been recruited
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nordfjord Psychiatric Centre
- Sponsor type
- University, hospital or other
- Collaborators
- H. Lundbeck A/S
- Investigators
- Trond F. Aarre, MD, Principal investigator, Nordfjord Psychiatric Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00464191
- Sponsor's protocol ID
- EudraCT 2005-004357-94
- Other IDs
- Lundbeck 10968, NPS 2005-1
- Status last verified
- Sep 2009
- First submitted
- 20 Apr 2007
- Last updated
- 21 Sep 2009
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Escitalopram in Bipolar Depression: a Placebo-controlled Study of Acute and Maintenance Treatment
- ClinicalTrials.gov ID
- NCT00464191
- Acronym / sponsor ID
- EudraCT 2005-004357-94
- Conditions
- Bipolar Disorder
- Keywords
- bipolar depression, SSRI, escitalopram, bipolar disorder, antidepressant, treatment trial, RCT
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study has been terminated because too few patients have been recruited
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Nordfjord Psychiatric CentreUniversity, hospital or other
- Collaborators
- H. Lundbeck A/S
- Study start
- Apr 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 23 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Funding: An investigator-initiated trial funded by H. Lundbeck AS.
Study design: Prospective, randomised, placebo-controlled parallel-group multicenter study.
Aim: To investigate efficacy and side effects (especially mood switches) of escitalopram,a selective serotonin reuptake inhibitor, in the acute and maintenance treatment of bipolar depression.
Hypotheses:
- Escitalopram, given in addition to mood stabilising medications, is significantly more efficacious, measured by response and remission rates than placebo in bipolar depression (the acute phase study).
- Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
- The incidence of "mood switching" (defined as development of mixed episodes, mania, or hypomania according to DSM-IV criteria) do not differ significantly between escitalopram and placebo in either the acute or the continuation phases.
Patients: In- and outpatients receiving care in the specialised psychiatric services of Western Norway. The population is intended to be representative of the patients treated for bipolar depression in ordinary specialist care. Patients must have a MADRS score of at least 20 at baseline. Patients with ongoing substance abuse or dependence, organic mental illness, and non-affective psychotic symptoms are excluded.
Medication: Escitalopram 10-20 mg daily or placebo in addition to mood stabilisers. The dose of mood stabilisers must have been constant for the last six weeks prior to randomisation.
Method: Phase 1 is a eight-week acute treatment trial with six clinical assessments. Patients treated with escitalopram who have not responded after eight weeks (defined by at least 50% reduction of MADRS score compared to baseline) leave the study. Placebo non-responders are treated openly with escitalopram and repeat phase 1. Responders are re-randomised to 32 weeks of maintenance treatment (phase 2). Phase 2 has nine clinical assessments. Patients who develop hypomania, mania or depressive episodes (defined as episodes meeting DSM-IV criteria for Major Depressive Episode with MADRS scores of at least 20 points) leave the study in this phase. Patients leaving the study prematurely will be offered alternative treatment.
Detailed description
Aims
The study has two main aims:
- To compare the efficacy and the risk of "mood switching" of escitalopram and placebo in the acute phase treatment of bipolar depression in patients already taking mood stabilising medication.
- To compare the efficacy of escitalopram and placebo in continuation phase therapy for bipolar depression using a placebo-controlled discontinuation design. The study will compare the occurrence of syndromal and subsyndromal relapses, mixed states, mania, hypomania, and "rapid cycling" in a seven months' maintenance study following response to acute phase treatment.
Hypotheses
- Escitalopram, given in addition to mood stabilising medications, is significantly more efficacious, measured by response and remission rates than placebo in bipolar depression (the acute phase study).
- Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
- The incidence of "mood switching" (defined as development of mixed episodes, mania, or hypomania according to DSM-IV criteria do not differ significantly between escitalopram and placebo in either the acute or the continuation phases.
Design This is a multi-center RCT with parallel-group design. The study compares the efficacy of placebo and escitalopram, given as add-on to mood stabilising medications in patients with bipolar depression without non-affective psychotic symptoms according to DSM-IV, and with a baseline MADRS score of ≥ 20 points.
The study has two phases. The acute phase study lasts for eight weeks and compares the efficacy of escitalopram and placebo on depressive symptoms in bipolar depression. Response is defined as at least 50% improvement on the MADRS compared to the baseline score. Responders to escitalopram are re-randomised to escitalopram or placebo for the continuation phase while placebo responders continue taking placebo for the continuation phase. Patients on escitalopram who do not respond in the acute phase leave the study, whereas placebo non-responders are treated openly with escitalopram and repeat phase 1. Responders to this open-label treatment are then re-randomised double blind to escitalopram or placebo for the continuation study.
The continuation phase study lasts for 32 weeks. Patients who responded to placebo in the acute phase continue placebo and their usual mood stabilising medication for the remainder of the study. Those who responded to escitalopram are re-randomised to continue taking placebo or escitalopram in unchanged doses. Patients who develop new mood episodes (DSM-IV-defined major depressive episode, mania, hypomania, or mixed episodes) or MADRS score ≥ 20 points leave the study.
Method Screening includes sociodemographic variables, medical and psychiatric history, diagnosis made on the basis of clinical interview and verified by the MINI, symptom intensity measured by the MADRS,), results of medical examination and laboratory tests (ECG, height, weight, blood pressure and blood tests). Sociodemographic variables include age, gender, previous and concomitant disorders, course and treatment of mental disorders, bipolar disorder type (I or II), age of onset and history of psychotropic medication use.
Study procedure As soon as the blood samples are analysed, eligible patients can be randomised. They are rated on the MADRS, Clinical Global Impressions (CGI), Inventory of Depressive Symptoms - Self Report (IDS-SR), Medical Outcomes Study Short Form 12 (SF-12), Global Assessment of Functioning (GAF) and Sheehan Disability Inventory (SDI) at the baseline visit. Study medication is dispensed. The patients will return to further visits as shown below. Patients will receive study medication for a maximum of 40 weeks. Adverse events and concomitant medications are recorded.
Assessments
The following assessments will be carried out::
- MADRS, GAF, IDS-RS, and CGI-I at week 1, 2, 4, 6, 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
- SDI and QLDS at week 8 and 40
- Diagnostic criteria for Mania and Hypomania at week 1, 2, 4, 6, 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
- Diagnostic criteria for Major Depressive Episode at week 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
For the acute study, response and remission rates as assessed by the MADRS are the primary outcome measures. CGI-Improvement and IDS-SR are secondary outcome measures. In the continuation study, primary outcome measures include emergence of major depressive episodes and mania/hypomania, while time spent at different depressive symptom levels as assessed by the DSM-IV diagnostic criteria are secondary outcome measures.
Definitions Response: at least a 50% reduction of the baseline MADRS score at the end of phase 1 if the patient has completed at least four weeks of the study. CGI-I 1 or 2 at the end of phase 1.
Remission: MADRS score of 12 or less at the end of the acute phase if the patient has completed at least four weeks of the study.
New episode: A patient who has previously responded to treatment meets the DSM-IV criteria for Major Depressive Episode. The patient must score at least 15 points on the MADRS and have a CGI-S score of 3 or more during this episode.
Mania and hypomania: by DSM-IV criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with bipolar disorder in major depressive episode according to DSM-IV
- MADRS score of at least 20 points at screening and baseline
- 18-70 years of age
- Unchanged dose of mood stabilising medication for at least six weeks prior to inclusion
- Voluntary, informed and written consent
Key exclusion criteria (15 listed)
- Non-affective psychotic symptoms at screening
- Pregnancy or breast-feeding
- Fertile women without appropriate contraception (the pill, IUD, or contraceptive injection)
- Substance dependence during the last three months prior to baseline
- Mental retardation and organic brain disorders
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 |
|---|---|---|
| escitalopram | Drug | – |
Primary outcome
Phase 1:
response rates
remission rates
Phase 2:
emergence of major depressive episodes
emergence of mania, hypomania, and mixed states.
5 secondary outcomes
Phase 1:
CGI-Improvement
change on the IDS-SR
Phase 2:
Time spent at different depressive symptom levels as assessed by the DSM-IV diagnostic criteria.
Results and safety
The study was stopped early (reason given: The study has been terminated because too few patients have been recruited). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2009.
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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.
Trond F. Aarre, MD principal investigator
Nordfjord Psychiatric Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing escitalopram in people with Bipolar Disorder, run by Nordfjord Psychiatric Centre at 1 site in Norway.
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 15 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: stopped early, as of the sponsor's last update on 21 Sep 2009. 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 Norway. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study has been terminated because too few patients have been recruited). Results are not available in the source record.
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?
Phase 1:. The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Sep 2009.