Trial Outcomes & Findings for Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (NCT NCT01407094)

Last Updated: 2018-12-26

Results Overview

The Hamilton Rating Scale for depression is a measure of depressive severity (HAM-D17; HDRS) * Scores range from 0-52 * Lower scores indicate less depressive symptomatology, and so are the more desirable.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

296 participants

Primary outcome timeframe

Week 8

Results posted on

2018-12-26

Participant Flow

Final enrollment Stage 1: 296 (146 SERT, 150 PBO). Individuals who responded to their Stage 1 treatment remained on that treatment in Stage 2. Individuals who did not respond to their Stage 1 treatment were switched to a different treatment in Stage 2.

Participant milestones

Participant milestones
Measure	Sertraline SSRI monotherapy Sertraline: 50-200mg/day	Placebo Placebo control Placebo: 1-4 pills per day	BupropionXL BupropionXL 150-450 mg/day Other names: WelbutrinXL
Stage 1 STARTED	146	150	0
Stage 1 COMPLETED	112	123	0
Stage 1 NOT COMPLETED	34	27	0
Stage 2 STARTED	134	46	53
Stage 2 COMPLETED	113	35	38
Stage 2 NOT COMPLETED	21	11	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sertraline n=146 Participants SSRI monotherapy Sertraline: 50-200mg/day	Placebo n=150 Participants Placebo control Placebo: 1-4 pills per day	BupropionXL BupropionXL 150-450mg/day	Total n=296 Participants Total of all reporting groups
Age, Categorical <=18 years	6 Participants n=93 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.	4 Participants n=4 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.	—	10 Participants n=483 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.
Age, Categorical Between 18 and 65 years	139 Participants n=93 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.	145 Participants n=4 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.	—	284 Participants n=483 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.
Age, Categorical >=65 years	1 Participants n=93 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.	1 Participants n=4 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.	—	2 Participants n=483 Participants • Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed.
Age, Continuous	37.2 years STANDARD_DEVIATION 13.8 • n=93 Participants	36.9 years STANDARD_DEVIATION 12.8 • n=4 Participants	—	37.05 years STANDARD_DEVIATION 13.3 • n=483 Participants
Sex: Female, Male Female	102 Participants n=93 Participants • Measure Analysis Population Description: Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed	92 Participants n=4 Participants • Measure Analysis Population Description: Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed	—	194 Participants n=483 Participants • Measure Analysis Population Description: Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed
Sex: Female, Male Male	44 Participants n=93 Participants • Measure Analysis Population Description: Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed	58 Participants n=4 Participants • Measure Analysis Population Description: Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed	—	102 Participants n=483 Participants • Measure Analysis Population Description: Of the 299 participants who were randomized, 3 were randomized but did not meet criteria, resulting in 296 who were randomized and assessed
Region of Enrollment United States	146 participants n=93 Participants	150 participants n=4 Participants	—	296 participants n=483 Participants

PRIMARY outcome

Timeframe: Week 8

Population: Note subjects in the efficacy trial were those that completed 8 weeks of treatment, 115 in the sertraline group, and 123 in the placebo group. SERT had 34 wash-outs, PBO had 27.

Outcome measures

Outcome measures
Measure	Sertraline n=146 Participants SSRI monotherapy Sertraline: 50-200mg/day	Placebo n=150 Participants Placebo control Placebo: 1-4 pills per day	BupropionXL BupropionXL 150-450mg/day
Hamilton Rating Scale for Depression	11.06 units on a scale Standard Deviation 6.71	12.52 units on a scale Standard Deviation 7.68	—

Adverse Events

Sertraline

Serious events: 10 serious events

Other events: 233 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 89 other events

Deaths: 0 deaths

BupropionXL

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sertraline n=283 participants at risk SSRI monotherapy Sertraline: 50-200mg/day	Placebo n=196 participants at risk Placebo control Placebo: 1-4 pills per day	BupropionXL n=53 participants at risk BupropionXL 150-450 mg/day
Endocrine disorders ER Visit	0.00% 0/283 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.51% 1/196 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Gastrointestinal disorders ER Visit	0.35% 1/283 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/196 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
General disorders ER Visit	0.35% 1/283 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/196 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Psychiatric disorders Suicidality	0.00% 0/283 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.51% 1/196 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Psychiatric disorders Panic attack	0.00% 0/283 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.51% 1/196 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Reproductive system and breast disorders Pregnancy	0.35% 1/283 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/196 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Cardiac disorders ER Visit	0.35% 1/283 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/196 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Psychiatric disorders ER Visit	0.35% 1/283 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/196 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Nervous system disorders Seizure	0.00% 0/283 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/196 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	1.9% 1/53 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Psychiatric disorders Hospitalization	0.35% 1/283 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/196 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).

Other adverse events

Other adverse events
Measure	Sertraline n=283 participants at risk SSRI monotherapy Sertraline: 50-200mg/day	Placebo n=196 participants at risk Placebo control Placebo: 1-4 pills per day	BupropionXL n=53 participants at risk BupropionXL 150-450 mg/day
Gastrointestinal disorders Diarrhea	12.0% 34/283 • Number of events 34 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	5.6% 11/196 • Number of events 11 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	3.8% 2/53 • Number of events 2 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
General disorders Dizziness	4.2% 12/283 • Number of events 12 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	3.1% 6/196 • Number of events 6 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	11.3% 6/53 • Number of events 6 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
General disorders Fatigue	4.6% 13/283 • Number of events 13 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	1.0% 2/196 • Number of events 2 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	1.9% 1/53 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
General disorders Dry Mouth	11.7% 33/283 • Number of events 33 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	4.1% 8/196 • Number of events 8 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	0.00% 0/53 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
General disorders Headaches	14.5% 41/283 • Number of events 41 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	23.5% 46/196 • Number of events 46 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	17.0% 9/53 • Number of events 9 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
General disorders Insomnia	10.6% 30/283 • Number of events 30 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	1.5% 3/196 • Number of events 3 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	1.9% 1/53 • Number of events 1 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
General disorders Nausea	20.1% 57/283 • Number of events 57 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	5.1% 10/196 • Number of events 10 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	9.4% 5/53 • Number of events 5 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).
Cardiac disorders Palpitations	4.6% 13/283 • Number of events 13 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	1.5% 3/196 • Number of events 3 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).	5.7% 3/53 • Number of events 3 • 8 weeks for each Stage (1 and 2) For both Serious and Other adverse events: SERT total is the sum of Stages 1 or 2, Treatment A plus Treatment D (210+73); PBO total is the sum of Stages 1 or 2, Treatment B (150+46). BUP was only used during Stage 2 (Treatment C).

Additional Information

Dr. Madhukar H. Trivedi

University of Texas Southwestern Medical Center

Phone: 214-648-0188

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place