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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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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. To do this, the investigators will re-analyze a previous clinical trial that evaluated lamotrigine as a treatment for bipolar II depression (GSK-SCA100223; NCT00274677).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lamotrigine - melancholic depression | Experimental | Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day. |
|
| Placebo - melancholic depression | Placebo Comparator | Participants with melancholic depression who were randomly assigned to receive a placebo comparator. |
|
| Lamotrigine - nonmelancholic depression | Experimental | 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. |
|
| Placebo - nonmelancholic depression | Placebo Comparator | Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lamotrigine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores | 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 |
| Hamilton Depression Rating Scale (HAMD-17) Change Scores | 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 |
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Eight weeks |
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Seven weeks |
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Six weeks |
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Five weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rudy C Bowen, FRCPC | University of Saskatchewan | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Psychiatry, Royal University Hospital | Saskatoon | Saskatchewan | S7N0W8 | Canada |
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| Label | URL |
|---|---|
| The ClinicalTrials.gov posting for the original study (GSK-SCA100223; NCT00274677) from which data for the present study was obtained. | View source |
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Patient-level data for the study (GSK-SCA100223; NCT00274677) is available through www.clinicalstudydatarequest.com.
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This study only analyzed data from treatment completers in the original study, NCT00274677. The original study enrolled 221 participants, with 150 completing the trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lamotrigine - Melancholic Depression | Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day. Lamotrigine: 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. |
| FG001 | Placebo - Melancholic Depression | Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets |
| FG002 | 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. Lamotrigine: 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. |
| FG003 | Placebo - Nonmelancholic Depression | Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lamotrigine - Melancholic Depression | Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day. Lamotrigine: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores | 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. | Posted | Mean | Standard Deviation | score on a scale | Eight weeks |
|
8 weeks.
We have combined the two lamotrigine arms (melancholic and nonmelancholic) into one group, and also the two placebo arms (melancholic and nonmelancholic) into one group. We did not analyze safety data by melancholic status, so we are only able to report the original safety results (which was stratified by treatment condition but not melancholic status).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lamotrigine | The data is from 109 participant that were randomized in the original trial. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment |
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Evyn Peters | Univeristy of Saskatchewan | 13062904493 | evyn.peters@usask.ca |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D001714 | Bipolar Disorder |
| D003866 | Depressive Disorder |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
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| ID | Term |
|---|---|
| D000077213 | Lamotrigine |
| ID | Term |
|---|---|
| D014227 | Triazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Placebos | Drug | Placebo tablets |
|
|
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Four weeks |
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Three weeks |
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Two weeks |
| Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | One week |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Eight weeks |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Seven weeks |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Six weeks |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Five weeks |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Four weeks |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Three weeks |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Two weeks |
| Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | One week |
| BG001 |
| Placebo - Melancholic Depression |
Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets |
| BG002 | 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. Lamotrigine: 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. |
| BG003 | Placebo - Nonmelancholic Depression | Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants with melancholic depression who were randomly assigned to receive a placebo comparator.
Placebos: Placebo tablets
| OG002 | 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. Lamotrigine: 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. |
| OG003 | Placebo - Nonmelancholic Depression | Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets |
|
|
|
| Primary | Hamilton Depression Rating Scale (HAMD-17) Change Scores | 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. | Posted | Mean | Standard Deviation | score on a scale | Eight weeks |
|
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Eight weeks |
|
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Seven weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Six weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Five weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Four weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Three weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Two weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) | Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | One week |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Eight weeks |
|
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Seven weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Six weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Five weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Four weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Three weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | Two weeks |
|
|
|
| Primary | Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) | Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%. | Posted | Count of Participants | Participants | One week |
|
|
|
| 0 |
| 109 |
| 0 |
| 109 |
| 88 |
| 109 |
| EG001 | Placebo | The data is from 109 participant that were randomized in the original trial. | 0 | 109 | 5 | 109 | 85 | 109 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | Non-systematic Assessment |
|
| Agitation | Psychiatric disorders | Non-systematic Assessment |
|
| Suicide attempt | Psychiatric disorders | Non-systematic Assessment |
|
| Dry mouth | General disorders | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | Non-systematic Assessment |
|
| Nasopharyngitis | General disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dizziness | General disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Sedation | General disorders | Non-systematic Assessment |
|
| Somnolence | General disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D001523 |
| Mental Disorders |
Weighted Cox regression with treatment condition (lamotrigine vs. placebo) predicting treatment response. Response is defined as a score reduction of at least 50% from baseline. The outcome variable is binary coded with "1" being a response at anytime point and "0" indicating no response. |
| Regression, Cox |
| .53 |
| Cox Proportional Hazard |
| 1.08 |
| Standard Error of the Mean |
| .12 |
| 2-Sided |
| Superiority |
Weighted Cox regression with treatment condition (lamotrigine vs. placebo) predicting treatment response. Response is defined as a score reduction of at least 50% from baseline. The outcome variable is binary coded with "1" being a response at any time point and "0" indicating no response. |
| Regression, Cox |
| .73 |
| Cox Proportional Hazard |
| 1.05 |
| Standard Error of the Mean |
| .13 |
| 2-Sided |
| Superiority |