Trial Outcomes & Findings for Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine (NCT NCT02989727)

NCT ID: NCT02989727

Last Updated: 2019-02-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 150 participants
• Primary outcome timeframe: Eight weeks
• Results posted on: 2019-02-15

Participant Flow

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

Participant milestones

Measure	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.	Placebo - Melancholic Depression Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	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.	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
Overall Study STARTED	46	44	30	30
Overall Study COMPLETED	46	44	30	30
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine

Baseline characteristics by cohort

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Total n=150 Participants Total of all reporting groups
Age, Continuous	38.2 years STANDARD_DEVIATION 12.5 • n=93 Participants	37.8 years STANDARD_DEVIATION 10.9 • n=4 Participants	41.2 years STANDARD_DEVIATION 10.6 • n=27 Participants	35.8 years STANDARD_DEVIATION 11.2 • n=483 Participants	38.2 years STANDARD_DEVIATION 11.4 • n=36 Participants
Sex: Female, Male Female	31 Participants n=93 Participants	32 Participants n=4 Participants	19 Participants n=27 Participants	17 Participants n=483 Participants	99 Participants n=36 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	12 Participants n=4 Participants	11 Participants n=27 Participants	13 Participants n=483 Participants	51 Participants n=36 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores	-15.7 score on a scale Standard Deviation 10.8	-13.8 score on a scale Standard Deviation 11.6	-16.0 score on a scale Standard Deviation 10.5	-15.5 score on a scale Standard Deviation 9.93

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Hamilton Depression Rating Scale (HAMD-17) Change Scores	-13.5 score on a scale Standard Deviation 7.92	-10.9 score on a scale Standard Deviation 9.52	-13.0 score on a scale Standard Deviation 7.59	-10.6 score on a scale Standard Deviation 6.55

PRIMARY outcome

Timeframe: Eight weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	28 Participants	22 Participants	20 Participants	16 Participants

PRIMARY outcome

Timeframe: Seven weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	27 Participants	21 Participants	20 Participants	20 Participants

PRIMARY outcome

Timeframe: Six weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	28 Participants	19 Participants	15 Participants	13 Participants

PRIMARY outcome

Timeframe: Five weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	25 Participants	19 Participants	12 Participants	9 Participants

PRIMARY outcome

Timeframe: Four weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	14 Participants	16 Participants	9 Participants	8 Participants

PRIMARY outcome

Timeframe: Three weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	11 Participants	10 Participants	8 Participants	8 Participants

PRIMARY outcome

Timeframe: Two weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	6 Participants	6 Participants	3 Participants	4 Participants

PRIMARY outcome

Timeframe: One week

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)	5 Participants	3 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: Eight weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	25 Participants	22 Participants	20 Participants	14 Participants

PRIMARY outcome

Timeframe: Seven weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	28 Participants	19 Participants	15 Participants	18 Participants

PRIMARY outcome

Timeframe: Six weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	29 Participants	17 Participants	14 Participants	11 Participants

PRIMARY outcome

Timeframe: Five weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	22 Participants	19 Participants	10 Participants	9 Participants

PRIMARY outcome

Timeframe: Four weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	16 Participants	13 Participants	9 Participants	11 Participants

PRIMARY outcome

Timeframe: Three weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	11 Participants	9 Participants	8 Participants	7 Participants

PRIMARY outcome

Timeframe: Two weeks

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	7 Participants	6 Participants	5 Participants	4 Participants

PRIMARY outcome

Timeframe: One week

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

Outcome measures

Measure	Lamotrigine - Melancholic Depression n=46 Participants 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.	Placebo - Melancholic Depression n=44 Participants Participants with melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets	Lamotrigine - Nonmelancholic Depression n=30 Participants 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.	Placebo - Nonmelancholic Depression n=30 Participants Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator. Placebos: Placebo tablets
Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)	3 Participants	2 Participants	1 Participants	1 Participants

Adverse Events

Lamotrigine

Serious events: 0 serious events

Other events: 88 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 85 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lamotrigine n=109 participants at risk The data is from 109 participant that were randomized in the original trial.	Placebo n=109 participants at risk The data is from 109 participant that were randomized in the original trial.
Skin and subcutaneous tissue disorders Cellulitis	0.00% 0/109 • 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).	0.92% 1/109 • Number of events 1 • 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).
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/109 • 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).	0.92% 1/109 • Number of events 1 • 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).
Psychiatric disorders Suicidal ideation	0.00% 0/109 • 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).	1.8% 2/109 • Number of events 2 • 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).
Psychiatric disorders Agitation	0.00% 0/109 • 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).	0.92% 1/109 • Number of events 1 • 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).
Psychiatric disorders Suicide attempt	0.00% 0/109 • 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).	0.92% 1/109 • Number of events 1 • 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).

Other adverse events

Measure	Lamotrigine n=109 participants at risk The data is from 109 participant that were randomized in the original trial.	Placebo n=109 participants at risk The data is from 109 participant that were randomized in the original trial.
Nervous system disorders Headache	27.5% 30/109 • 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).	35.8% 39/109 • 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).
General disorders Dry mouth	9.2% 10/109 • 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).	6.4% 7/109 • 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).
Psychiatric disorders Insomnia	8.3% 9/109 • 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).	6.4% 7/109 • 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).
General disorders Nasopharyngitis	0.00% 0/109 • 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).	8.3% 9/109 • 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).
Gastrointestinal disorders Nausea	7.3% 8/109 • 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).	13.8% 15/109 • 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).
General disorders Dizziness	6.4% 7/109 • 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).	7.3% 8/109 • 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).
Skin and subcutaneous tissue disorders Rash	6.4% 7/109 • 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).	6.4% 7/109 • 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).
Respiratory, thoracic and mediastinal disorders Cough	5.5% 6/109 • 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).	4.6% 5/109 • 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).
General disorders Sedation	5.5% 6/109 • 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).	1.8% 2/109 • 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).
General disorders Somnolence	5.5% 6/109 • 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).	4.6% 5/109 • 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).
General disorders Fatigue	2.8% 3/109 • 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).	6.4% 7/109 • 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).
Gastrointestinal disorders Vomiting	1.8% 2/109 • 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).	5.5% 6/109 • 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).

Additional Information

Dr. Evyn Peters

Univeristy of Saskatchewan

Phone: 13062904493

Email: evyn.peters@usask.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place