Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine

• Sponsor: University of Saskatchewan (Other)
• Overall Status: Completed
• CT.gov ID: NCT02989727
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 150
• Location: 1
• Arms: 4
• Duration (Months): 169
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Depression; Bipolar Disorder; Bipolar Depression; Melancholia; Lamotrigine	Drug: Lamotrigine; Drug: Placebos	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine: Results From an 8-week, Multicenter, Double-blind, Placebo-controlled Trial
• Study Start Date: Nov 1, 2003
• Actual Primary Completion Date: Aug 1, 2005
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

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.	Drug: 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.; Other Names: Lamictal
Placebo Comparator: Placebo - melancholic depression Participants with melancholic depression who were randomly assigned to receive a placebo comparator.	Drug: Placebos; Placebo tablets; Other Names: Placebo
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.	Drug: 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.; Other Names: Lamictal
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.	Drug: Placebos; Placebo tablets; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores [Eight weeks]

   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.

2. Hamilton Depression Rating Scale (HAMD-17) Change Scores [Eight weeks]

   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.

3. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [Eight weeks]

   Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

4. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [Seven weeks]

   Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

5. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [Six weeks]

   Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

6. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [Five weeks]

   Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

7. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [Four weeks]

   Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

8. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [Three weeks]

   Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

9. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [Two weeks]

   Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

10. Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) [One week]

    Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.

11. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [Eight weeks]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

12. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [Seven weeks]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

13. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [Six weeks]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

14. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [Five weeks]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

15. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [Four weeks]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

16. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [Three weeks]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

17. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [Two weeks]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

18. Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17) [One week]

    Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients must provide written and informed consent.

2. 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.

3. 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.

4. Acceptable results (within two times the normal limit) on laboratory screening tests (e.g., thyroid function).

Exclusion Criteria:

1. Active suicidality.

2. History of non-response to antidepressant treatment, or any previous treatment with lamotrigine.

3. History of substance dependence in the past year, or abuse within the 4 weeks prior to study entry.

4. Rapid cycling bipolar disorder.

5. Receiving additional psychoactive medication (not including lorazepam for agitation), or has started a new course of psychotherapy within the last month.

6. Received treatment for an anxiety or eating disorder within the last 12 months.

7. Investigational drug use within the last month.

8. History of epilepsy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Psychiatry, Royal University Hospital	Saskatoon	Saskatchewan	Canada	S7N0W8

Sponsors and Collaborators

• University of Saskatchewan
• GlaxoSmithKline

Investigators

• Study Director: Rudy C Bowen, FRCPC, University of Saskatchewan

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The ClinicalTrials.gov posting for the original study (GSK-SCA100223; NCT00274677) from which data for the present study was obtained.

Publications

None provided.

• Responsible Party: Evyn Peters, Resident, University of Saskatchewan
• ClinicalTrials.gov Identifier: NCT02989727
• Other Study ID Numbers: GSK-SCA100223
• First Posted: Dec 12, 2016
• Last Update Posted: Feb 15, 2019
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Lamotrigine

Study Results

Participant Flow

Recruitment Details	This study only analyzed data from treatment completers in the original study, NCT00274677. The original study enrolled 221 participants, with 150 completing the trial.

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Period Title: Overall Study
STARTED	46	44	30	30
COMPLETED	46	44	30	30
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression	Total
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Total of all reporting groups
Overall Participants	46	44	30	30	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.2 (12.5)	37.8 (10.9)	41.2 (10.6)	35.8 (11.2)	38.2 (11.4)
Sex: Female, Male (Count of Participants)
Female	31 67.4%	32 72.7%	19 63.3%	17 56.7%	99 66%
Male	15 32.6%	12 27.3%	11 36.7%	13 43.3%	51 34%

Outcome Measures

1. Primary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores
Description	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.
Time Frame	Eight weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Mean (Standard Deviation) [score on a scale]	-15.7 (10.8)	-13.8 (11.6)	-16.0 (10.5)	-15.5 (9.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lamotrigine - Melancholic Depression, Placebo - Melancholic Depression, Lamotrigine - Nonmelancholic Depression, Placebo - Nonmelancholic Depression
	Comments	Weighted ANOVA models were used to compare change scores between lamotrigine and placebo groups while testing for interactions by melancholic status. The estimate and test reported is for the the interaction between treatment condition and melancholic status.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.59
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	ANOVA estimate
	Estimated Value	1.88
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.51
	Estimation Comments

2. Primary Outcome

Title	Hamilton Depression Rating Scale (HAMD-17) Change Scores
Description	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.
Time Frame	Eight weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Mean (Standard Deviation) [score on a scale]	-13.5 (7.92)	-10.9 (9.52)	-13.0 (7.59)	-10.6 (6.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lamotrigine - Melancholic Depression, Placebo - Melancholic Depression, Lamotrigine - Nonmelancholic Depression, Placebo - Nonmelancholic Depression
	Comments	Weighted ANOVA models were used to compare change scores between lamotrigine and placebo groups while testing for interactions by melancholic status. The estimate and test reported is for the the interaction between treatment condition and melancholic status.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.84
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	ANOVA estimate
	Estimated Value	0.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.56
	Estimation Comments

3. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Eight weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	28 60.9%	22 50%	20 66.7%	16 53.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lamotrigine - Melancholic Depression, Placebo - Melancholic Depression
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.08
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .10
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lamotrigine - Nonmelancholic Depression, Placebo - Nonmelancholic Depression
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.53
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.08
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .12
	Estimation Comments

4. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Seven weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	27 58.7%	21 47.7%	20 66.7%	20 66.7%

5. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Six weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	28 60.9%	19 43.2%	15 50%	13 43.3%

6. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Five weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	25 54.3%	19 43.2%	12 40%	9 30%

7. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	14 30.4%	16 36.4%	9 30%	8 26.7%

8. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Three weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	11 23.9%	10 22.7%	8 26.7%	8 26.7%

9. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Two weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	6 13%	6 13.6%	3 10%	4 13.3%

10. Primary Outcome

Title	Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	One week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	5 10.9%	3 6.8%	2 6.7%	2 6.7%

11. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Eight weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	25 54.3%	22 50%	20 66.7%	14 46.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lamotrigine - Melancholic Depression, Placebo - Melancholic Depression
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.02
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .11
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lamotrigine - Nonmelancholic Depression, Placebo - Nonmelancholic Depression
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.73
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .13
	Estimation Comments

12. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Seven weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	28 60.9%	19 43.2%	15 50%	18 60%

13. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Six weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	29 63%	17 38.6%	14 46.7%	11 36.7%

14. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Five weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	22 47.8%	19 43.2%	10 33.3%	9 30%

15. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	16 34.8%	13 29.5%	9 30%	11 36.7%

16. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Three weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	11 23.9%	9 20.5%	8 26.7%	7 23.3%

17. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	Two weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	7 15.2%	6 13.6%	5 16.7%	4 13.3%

18. Primary Outcome

Title	Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
Description	Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
Time Frame	One week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lamotrigine - Melancholic Depression	Placebo - Melancholic Depression	Lamotrigine - Nonmelancholic Depression	Placebo - Nonmelancholic Depression
Arm/Group Description	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.	Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Measure Participants	46	44	30	30
Count of Participants [Participants]	3 6.5%	2 4.5%	1 3.3%	1 3.3%

Adverse Events

Time Frame	8 weeks.
Adverse Event Reporting Description	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).
Arm/Group Title	Lamotrigine		Placebo
Arm/Group Description	The data is from 109 participant that were randomized in the original trial.		The data is from 109 participant that were randomized in the original trial.
All Cause Mortality
	Lamotrigine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/109 (0%)		0/109 (0%)
Serious Adverse Events
	Lamotrigine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/109 (0%)		5/109 (4.6%)
Psychiatric disorders
Suicidal ideation	0/109 (0%)	0	2/109 (1.8%)	2
Agitation	0/109 (0%)	0	1/109 (0.9%)	1
Suicide attempt	0/109 (0%)	0	1/109 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/109 (0%)	0	1/109 (0.9%)	1
Skin and subcutaneous tissue disorders
Cellulitis	0/109 (0%)	0	1/109 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Lamotrigine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/109 (80.7%)		85/109 (78%)
Gastrointestinal disorders
Nausea	8/109 (7.3%)		15/109 (13.8%)
Vomiting	2/109 (1.8%)		6/109 (5.5%)
General disorders
Dry mouth	10/109 (9.2%)		7/109 (6.4%)
Nasopharyngitis	0/109 (0%)		9/109 (8.3%)
Dizziness	7/109 (6.4%)		8/109 (7.3%)
Sedation	6/109 (5.5%)		2/109 (1.8%)
Somnolence	6/109 (5.5%)		5/109 (4.6%)
Fatigue	3/109 (2.8%)		7/109 (6.4%)
Nervous system disorders
Headache	30/109 (27.5%)		39/109 (35.8%)
Psychiatric disorders
Insomnia	9/109 (8.3%)		7/109 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	6/109 (5.5%)		5/109 (4.6%)
Skin and subcutaneous tissue disorders
Rash	7/109 (6.4%)		7/109 (6.4%)

Limitations/Caveats

Short duration of trial in context of slow dosing regime Inability to assess other definitions of melancholia Sample of only bipolar II depression

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.