Escitalopram in Bipolar Depression: a Placebo-controlled Study of Acute and Maintenance Treatment

September 19, 2009 updated by: Nordfjord Psychiatric Centre

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:

  1. 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).
  2. Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
  3. 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Aims

The study has two main aims:

  1. 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.
  2. 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

  1. 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).
  2. Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
  3. 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::

  1. MADRS, GAF, IDS-RS, and CGI-I at week 1, 2, 4, 6, 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
  2. SDI and QLDS at week 8 and 40
  3. Diagnostic criteria for Mania and Hypomania at week 1, 2, 4, 6, 8, 9, 10, 12, 16, 20, 24, 28, 34 and 40
  4. 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Nordfjordeid, Norway, 6770
        • Nordfjord Psychiatric Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Phase 1:
response rates
remission rates
Phase 2:
emergence of major depressive episodes
emergence of mania, hypomania, and mixed states.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Phase 1:
Phase 2:
CGI-Improvement
change on the IDS-SR
Time spent at different depressive symptom levels as assessed by the DSM-IV diagnostic criteria.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nordfjord Psychiatric Centre

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
H. Lundbeck A/S

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Trond F. Aarre, MD, Nordfjord Psychiatric Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 20, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 23, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 21, 2009

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2009

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EudraCT 2005-004357-94
  • Lundbeck 10968
  • NPS 2005-1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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