- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02989727
Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine
Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine: Results From an 8-week, Multicenter, Double-blind, Placebo-controlled Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
Patients suffering from depression with melancholic symptoms (i.e., anhedonia, flat affect, diurnal mood variation, terminal insomnia, psychomotor disturbances, decreased weight/appetite, and excessive guilt) respond better to certain antidepressants. Melancholic symptoms also occur in bipolar depression, although they have received less research. Lamotrigine has been shown to alter some of the biological processes that are known to occur in melancholic depression. The purpose of this study is to determine if patients with melancholic bipolar II depression are more responsive to lamotrigine than patients with non-melancholic bipolar II depression.
This study will re-analyze data from a previous 8-week, randomized, placebo-controlled trial that evaluated lamotrigine as a treatment for bipolar II depression (GSK-SCA100223; NCT00274677). The original study data was made available by GlaxoSmithKline as part of an initiative to make clinical trials data available for research use. Access was applied for via https://www.clinicalstudydatarequest.com.
The analysis strategy will be comparable to the original study, although the investigators will first classify participants as suffering from either melancholic or non-melancholic depression. The diagnosis of melancholic depression was established according to baseline responses to the Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS), according to the DSM-IV-TR diagnostic criteria. HAMD-17 and MADRS change scores will be compared between the treatment and placebo groups using Analysis of Variance (ANOVA). Both ANOVA models will include a test for an interaction between treatment group (lamotrigine vs. placebo) and melancholic depression (melancholic depression vs. non-melancholic depression). To handle missing data, each ANOVA model will be computed with only complete-case data first and subsequently using inverse probability weights that account for the probability of drop out. Inverse probability weights will be created based on covariates that predict missing responses. HAMD-17 and MADRS response rates between the treatment and placebo groups will be evaluated with a Cox proportional hazard regression analysis. There will be two separate analyses, one including participants with melancholic depression, and one including participants with non-melancholic depression. Statistical models will also adjust for baseline depression severity, if participants with melancholic depression are found to have more severe depressive symptoms at baseline.
Given the delay between antidepressant initiation and response, trial-and-error prescribing is an inevitably lengthy process. The investigators hope the results of this study will enable more timely and effective treatment for patients with bipolar depression.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Saskatchewan
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Saskatoon, Saskatchewan, Canada, S7N0W8
- Department of Psychiatry, Royal University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must provide written and informed consent.
- Diagnosis of Bipolar II Disorder and currently depressed for minimum of the last 8 weeks, with a HAMD-17 score of at least 18 with scores of 3 or more on Items 1 or 7.
- For females, be of non-childbearing potential, or of childbearing potential with a negative pregnancy test at screening and agrees to one of (a) abstinence from sex two weeks prior and five days after drug continuation/discontinuation, (b) personal or partner sterilization, (c) one method of hormonal contraception, or (d) two barrier methods of contraception.
- Acceptable results (within two times the normal limit) on laboratory screening tests (e.g., thyroid function).
Exclusion Criteria:
- Active suicidality.
- History of non-response to antidepressant treatment, or any previous treatment with lamotrigine.
- History of substance dependence in the past year, or abuse within the 4 weeks prior to study entry.
- Rapid cycling bipolar disorder.
- Receiving additional psychoactive medication (not including lorazepam for agitation), or has started a new course of psychotherapy within the last month.
- Received treatment for an anxiety or eating disorder within the last 12 months.
- Investigational drug use within the last month.
- History of epilepsy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lamotrigine - melancholic depression
Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.
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Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.
Other Names:
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Placebo Comparator: Placebo - melancholic depression
Participants with melancholic depression who were randomly assigned to receive a placebo comparator.
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Placebo tablets
Other Names:
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Experimental: Lamotrigine - nonmelancholic depression
Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.
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Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.
Other Names:
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Placebo Comparator: Placebo - nonmelancholic depression
Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.
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Placebo tablets
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores
Time Frame: Eight weeks
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Scale scores range from 0 to 60. This outcome is a change score calculated by subtracting Baseline from Week 8 scores. Lower scores indicate greater improvement of depressive symptoms. |
Eight weeks
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Hamilton Depression Rating Scale (HAMD-17) Change Scores
Time Frame: Eight weeks
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Scale scores range from 0 to 52. This outcome is a change score calculated by subtracting Baseline from Week 8 scores. Lower scores indicate greater improvement of depressive symptoms. |
Eight weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Eight weeks
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Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
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Eight weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Seven weeks
|
Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
|
Seven weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Six weeks
|
Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
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Six weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Five weeks
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Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
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Five weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Four weeks
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Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
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Four weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Three weeks
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Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
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Three weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Two weeks
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Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
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Two weeks
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Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: One week
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Scale scores range from 0 to 60.
A response is defined as a score reduction from baseline of at least 50%.
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One week
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: Eight weeks
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Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
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Eight weeks
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: Seven weeks
|
Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
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Seven weeks
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: Six weeks
|
Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
|
Six weeks
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: Five weeks
|
Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
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Five weeks
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: Four weeks
|
Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
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Four weeks
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: Three weeks
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Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
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Three weeks
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: Two weeks
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Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
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Two weeks
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Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Time Frame: One week
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Scale scores range from 0 to 52.
A response is defined as a score reduction from baseline of at least 50%.
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One week
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Rudy C Bowen, FRCPC, University of Saskatchewan
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Bipolar and Related Disorders
- Depression
- Depressive Disorder
- Bipolar Disorder
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Membrane Transport Modulators
- Anticonvulsants
- Sodium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Lamotrigine
Other Study ID Numbers
- GSK-SCA100223
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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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