Study In Patients With Depression Not Responding to Selective Serotonin Re-uptake Inhibitors

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00296517
• Collaborator: (none)
• Enrollment: 325
• Locations: 62
• Arms: 2
• Actual Duration (Months): 26.3
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is designed to evaluate the efficacy and safety in depressive patients who did not respond sufficiently to selective serotonin re-uptake inhibitors (SSRI).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder	Drug: 323U66 (Bupropion Hydrochloride Sustained Release); Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 325 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical Evaluation of 323U66 SR in Patients With Depression - Placebo-controlled, Double-blind, Comparative Study in Patients With Depression Who Did Not Respond Sufficiently to Selective Serotonin Re-uptake Inhibitors
• Actual Study Start Date: Jan 19, 2006
• Actual Primary Completion Date: Mar 28, 2008
• Actual Study Completion Date: Mar 28, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Subjects with Major Depressive Disorder who were randomised to placebo to match Bupropion SR during the treatment period.	Drug: Placebo; Subjects with Major Depressive Disorder who were randomised to placebo to match Bupropion SR during the treatment period.
Experimental: Bupropion SR Subjects with Major Depressive Disorder who were randomized to take 100mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100mg dose of Bupropion morning and evening. Weeks 3 thru 12 received 150mg dose morning and evening. Week 1=dose level 1, 100 mg. Week 2=dose level 2, 200 mg. Weeks 3 - 12=dose level 3, 300 mg.	Drug: 323U66 (Bupropion Hydrochloride Sustained Release); Subjects with Major Depressive Disorder who were randomized to take 100mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100mg dose of Bupropion morning and evening. Weeks 3 thru 12 received 150mg dose morning and evening. Week 1=dose level 1, 100 mg. Week 2=dose level 2, 200 mg. Weeks 3 - 12=dose level 3, 300 mg.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score [Baseline and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).

Secondary Outcome Measures

1. Hamilton Depression Scale (HAM-D 17 Items) Total Score [Week 8 and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).

2. Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score at Week 8 and Total Score at Week 12 [Baseline to Week 8 and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).

3. Percentage of Change From Baseline of the Hamilton Depression (HAM-D 17 Items) Total Score at Weeks 8 and 12. [Baseline to Week 8 and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).

4. Percentage of Responders Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12 [Baseline to Week 8 and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill). Responders are defined as subjects with 50% or greater reduction from baseline in HAM-D total score.

5. Percentage of Remitters Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12 [Baseline to Week 8 and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill). Remitters are defined as subjects with HAM-D total score ≤ 7.

6. Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12 [Baseline to Week 8 and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2, with total HAM-D scores ranging from 0 (not ill) to 54 (severely ill).

7. Percentage of Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12 [Baseline to Week 8 and Week 12]

   The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2, with total HAM-D scores ranging from 0 (not ill) to 54 (severely ill).

8. Change From Baseline in Clinical Global Impressions - Severity of Illness (CGI-S) Scale at Weeks 1, 2, 3, 4, and 8 and 12 [Baseline to Weeks 1, 2, 3, 4, 8, and 12]

   The 7-point Clinical Global Impressions-Severity of Illness Scale (CGI-S) measures the severity of psychiatric symptoms. The following scores can be given: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill patients.

9. Percentage of Responders Based on the Clinical Global Impression - Global Improvement (CGI-I) Scale at Weeks 8 and 12 [Baseline to Week 8 and Week 12]

   The CGI-I assesses the investigator's impression of the patient's current illness. The time span is the week before the rating and the score ranges from 1 (very much improved) to 7 (very much worse). Responders are subjects that have a score of 1 (very much improved) or 2 (much improved) on the CGI-I.

10. Study Continuation Rate as Assessed by the Number of Participants at Risk at Week 12 [Week 12]

    Kaplan-Meier estimates were calculated using event or censoring and time to event or censoring. Participants at risk refers to participants with either a censoring or event time beyond the time point of interest (Week 12).

11. Safety: Adverse Events by Organ System Class, Intensity, and Frequency [Baseline to Week 12]

    Assessment of intensity was based on investigators/subinvestigator's clinical judgement per protocol instructions: Mild event, easily tolerated, with minimal discomfort and not interfering with Activities of Daily Living (ADLs); moderate event, with discomfort that interferes with ADLs; severe event, prevents ADLs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• [At the start of the pretreatment phase]

• Target disease: Patients diagnosed as having the following primary disease on the basis of DSM-IV-TR criteria.

• Major Depressive Disorder, Single Episode (296.2x) (excluding with psychotic features)

• Major Depressive Disorder, Recurrent (296.3x) (excluding with psychotic features)

• HAM-D (17 items) total score is >=16.

• Patients who have been treated with marketed paroxetine (Paxil®) at 20mg/day to 40mg/day for 4 weeks and more at the start of the pretreatment phase.

• Age: >=18 years old (at the time of informed consent) , <65 years old (at the start of treatment phase )

• Gender: Male or female.

• Inpatients or outpatients: Either

• Informed consent: The subject himself/herself must give written informed consent. However, if the subject is under 20 at the time of giving consent, both the subject himself/herself and his/her legally acceptable representative must give written informed consent.

[At the end of the pretreatment phase]

1. HAM-D (17 items) total score is ≥14.

2. Percentage of change from the start of the pretreatment phase in the HAM-D (17 items) total score is <50%

[At the start of the treatment phase]

1. HAM-D (17 items) total score is ≥14.

2. Percentage of change from the start of the pretreatment phase in the HAM-D (17 items) total score is <50%

Exclusion Criteria:

[At the start of the pre-treatment phase]

• Patients with a complication of glaucoma

• Patients concomitantly using a drug increasing the risk of bleeding and patients with bleeding tendency or predisposition to bleeding

• Patients with predisposition to seizure (who currently have or have a past history of seizure, febrile convulsive seizure in infancy, cerebral tumour, cerebrovascular disorder or head injury, who have a family history of idiopathic seizure, patients with diabetes who have been treated with oral hypoglycaemics or insulin, or who use drugs lowering the threshold of seizure).

• Patients who currently have or have a past history of the following disorders:

• Anorexia nervosa (DSM-IV-TR 307.1)

• Bulimia nervosa (DSM-IV-TR 307.51)

• Patients with a history of manic episode

• Patients with a past or current DSM- IV-TR diagnosis of schizophrenia or other psychotic disorder

• Patients with a current DSM-IV-TR Axis II diagnosis (e.g., antisocial or borderline personality disorder)

• Patients starting psychotherapy (except for supportive psychotherapy not aimed at therapeutic efficacy and unlikely to affect efficacy evaluation) and formal cognitive behaviour therapy within 5 weeks prior to the start of the pre-treatment phase

• Patients with a diagnosis of substance abuse (alcohol or drug) by the DSM-IV-TR criteria or with a diagnosis of substance dependence within 1 year prior to the start of the pre-treatment phase

• Patients who have received electroconvulsive therapy within 17 weeks prior to the start of the pre-treatment phase

• Patients who have taken MAO inhibitors (selegiline hydrochloride) within 2 weeks prior to the start of the pre-treatment phase

• Patients who have taken another investigational drug within 12 weeks prior to the start of the pre-treatment phase

• Female patients who are pregnant, possibly pregnant or are nursing, and those who want to become pregnant before 30 days after the last dose of the investigational product

• Patients who have attempted suicide within 17 weeks prior to the start of the pre-treatment phase, or patients for whom the score of suicide-related item No. 3 of HAM-D is >=3, or patients in whom the risk of suicide is judged to be high by the investigator (sub-investigator)

• Patients in whom the risk of homicide is judged to be high by the investigator (sub-investigator)

• Patients with a history of hypersensitivity to 323U66 and/or paroxetine

• Patients with serious cerebral disease

• Patients who have ECG or clinical evidence of any cardiac condition that the investigator (sub-investigator) feels may predispose the subject to ischemia or arrhythmia

• Patients with serious physical symptoms (i.e. cardiac/hepatic/renal disorder, hematopoietic disorder) The index of seriousness is Grade 3 of "Criteria for classification of seriousness of adverse drug reactions to pharmaceutical products, etc." (PAB/PSD No.80 in 1992).

• Patients with a history or complication of cancer or malignant tumour.

• Patients whose major depressive disorder is due to direct physiological effects of a general medical condition (for example, hypothyroidism, Parkinson's disease, chronic pain)

• Patients with systolic blood pressure of >=160 mmHg or diastolic blood pressure of

=100 mmHg

• Patients who are inappropriate for participating in the study in the judgement of the investigator (sub-investigator)

[At the start of the treatment phase]

1. Patients whose compliance of paroxetine during the pretreatment phase is less than 70%.

2. Patients who have ECG or clinical evidence of any cardiac condition that the investigator (sub-investigator) feels may predispose the subject to ischemia or arrhythmia

3. Patients with systolic blood pressure of >=160 mmHg or diastolic blood pressure of

=100 mmHg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Aichi		Japan	462-0831
2	GSK Investigational Site	Aichi		Japan	470-1141
3	GSK Investigational Site	Aichi		Japan	475-0074
4	GSK Investigational Site	Chiba		Japan	270-1613
5	GSK Investigational Site	Fukuoka		Japan	802-0006
6	GSK Investigational Site	Fukuoka		Japan	810-0001
7	GSK Investigational Site	Fukuoka		Japan	814-0180
8	GSK Investigational Site	Fukuoka		Japan	816-0801
9	GSK Investigational Site	Fukuoka		Japan	816-0864
10	GSK Investigational Site	Fukushima		Japan	960-0102
11	GSK Investigational Site	Fukushima		Japan	961-0021
12	GSK Investigational Site	Fukushima		Japan	963-0207
13	GSK Investigational Site	Hokkaido		Japan	002-8029
14	GSK Investigational Site	Hokkaido		Japan	004-0052
15	GSK Investigational Site	Hokkaido		Japan	004-0841
16	GSK Investigational Site	Hokkaido		Japan	047-0155
17	GSK Investigational Site	Hokkaido		Japan	060-0042
18	GSK Investigational Site	Hokkaido		Japan	060-0061
19	GSK Investigational Site	Hokkaido		Japan	062-0922
20	GSK Investigational Site	Hokkaido		Japan	063-0061
21	GSK Investigational Site	Hokkaido		Japan	063-0804
22	GSK Investigational Site	Hokkaido		Japan	080-0014
23	GSK Investigational Site	Hyogo		Japan	651-0092
24	GSK Investigational Site	Hyogo		Japan	651-0097
25	GSK Investigational Site	Hyogo		Japan	653-0841
26	GSK Investigational Site	Hyogo		Japan	657-0846
27	GSK Investigational Site	Ibaraki		Japan	300-0812
28	GSK Investigational Site	Ibaraki		Japan	311-3193
29	GSK Investigational Site	Ishikawa		Japan	920-0939
30	GSK Investigational Site	Kagawa		Japan	761-0793
31	GSK Investigational Site	Kanagawa		Japan	213-0001
32	GSK Investigational Site	Kanagawa		Japan	223-0052
33	GSK Investigational Site	Kanagawa		Japan	225-0011
34	GSK Investigational Site	Kanagawa		Japan	231-0023
35	GSK Investigational Site	Kanagawa		Japan	238-0042
36	GSK Investigational Site	Kumamoto		Japan	861-8002
37	GSK Investigational Site	Nagano		Japan	390-8510
38	GSK Investigational Site	Nara		Japan	639-0225
39	GSK Investigational Site	Okayama		Japan	700-0941
40	GSK Investigational Site	Osaka		Japan	530-0026
41	GSK Investigational Site	Osaka		Japan	571-0048
42	GSK Investigational Site	Osaka		Japan	576-0054
43	GSK Investigational Site	Osaka		Japan	582-0025
44	GSK Investigational Site	Osaka		Japan	589-0011
45	GSK Investigational Site	Osaka		Japan	590-0018
46	GSK Investigational Site	Tokyo		Japan	107-0052
47	GSK Investigational Site	Tokyo		Japan	108-0072
48	GSK Investigational Site	Tokyo		Japan	110-0005
49	GSK Investigational Site	Tokyo		Japan	114-0014
50	GSK Investigational Site	Tokyo		Japan	120-0033
51	GSK Investigational Site	Tokyo		Japan	141-0032
52	GSK Investigational Site	Tokyo		Japan	152-0012
53	GSK Investigational Site	Tokyo		Japan	154-0003
54	GSK Investigational Site	Tokyo		Japan	154-0004
55	GSK Investigational Site	Tokyo		Japan	160-0023
56	GSK Investigational Site	Tokyo		Japan	170-0002
57	GSK Investigational Site	Tokyo		Japan	170-0005
58	GSK Investigational Site	Tokyo		Japan	178-0063
59	GSK Investigational Site	Tokyo		Japan	194-0022
60	GSK Investigational Site	Tokyo		Japan	204-0022
61	GSK Investigational Site	Tottori		Japan	682-0023
62	GSK Investigational Site	Tottori		Japan	683-8504

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00296517
• Other Study ID Numbers: AK1102365
• First Posted: Feb 27, 2006
• Last Update Posted: Dec 4, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: depression; double-blind; placebo-controlled; bupropion hydrochloride; SSRI; comparative study; non-responder
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bupropion

Study Results

Participant Flow

Pre-assignment Detail	Pre-treatment period: Paroxetine 40 mg/day was administered for four weeks in subjects treated with marketed paroxetine between doses of 20 and 40 mg/day for four weeks or more prior to tapering pretreatment period. Tapering pretreatment period: Paroxetine was tapered down weekly by 10 mg/day in subjects who were progressed to treatment period.

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Period Title: Dose Level 1 - Week 1
STARTED	159	166
COMPLETED	159	166
NOT COMPLETED	0	0
Period Title: Dose Level 1 - Week 1
STARTED	159	166
COMPLETED	157	161
NOT COMPLETED	2	5
Period Title: Dose Level 1 - Week 1
STARTED	157	161
COMPLETED	112	99
NOT COMPLETED	45	62

Baseline Characteristics

Arm/Group Title	Placebo	Bupropion SR	Total
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.	Total of all reporting groups
Overall Participants	157	165	322
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.0 (8.91)	36.8 (9.28)	36.4 (9.10)
Sex: Female, Male (Count of Participants)
Female	69 43.9%	77 46.7%	146 45.3%
Male	88 56.1%	88 53.3%	176 54.7%
Region of Enrollment (participants) [Number]
Japan	157 100%	165 100%	322 (0) 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set was all subjects who entered the treatment phase with the exception of those who did not take any investigational products during the treatment phase and those who did not meet the major eligibility criteria of Major Depressive Disorder or those with no valid post baseline assessment. Week 12/LOCF placebo = 155, Bupropion SR = 160

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Baseline	19.8 (4.34)	19.4 (4.39)
Week 12 or Last Observation Carried Forward	14.7 (8.89)	14.6 (9.09)
Change from Baseline	-5.1 (8.02)	-4.9 (8.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bupropion SR
	Comments	Null Hypothesis: The population mean change from baseline on HAM-D total score at Week 12 of the placebo group is equal to the population mean change from baseline on HAMD total score at Week 12 of the Bupropion hydrochloride sustained release group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.805
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.2
	Confidence Interval	() 95%; -1.6 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Hamilton Depression Scale (HAM-D 17 Items) Total Score
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).
Time Frame	Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Week 8 Last Observation Carried Forward: placebo = 152, Bupropion = 160, Week 8 Observed Cases: placebo = 113, Bupropion = 106, Week 12 Observed Cases: placebo = 111, Bupropion = 98

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Week 8 Mean - Last Observation Carried Forward	15.8 (8.04)	15.4 (8.32)
Week 8 Mean - Observed Cases	13.3 (6.74)	12.1 (6.28)
Week 12 Mean - Observed Cases	11.3 (7.09)	10.3 (6.83)

3. Secondary Outcome

Title	Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score at Week 8 and Total Score at Week 12
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).
Time Frame	Baseline to Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Week 8 Last Observation Carried Forward: placebo = 152, Bupropion = 160, Week 8 Observed Cases: placebo = 113, Bupropion = 106, Week 12 Observed Cases: placebo = 111, Bupropion = 98

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Week 8 Mean - Last Observation Carried Forward	-4.1 (7.07)	-4.0 (7.60)
Week 8 Mean - Observed Cases	-6.4 (5.77)	-7.4 (5.75)
Week 12 Mean - Observed Cases	-8.3 (6.38)	-9.2 (5.98)

4. Secondary Outcome

Title	Percentage of Change From Baseline of the Hamilton Depression (HAM-D 17 Items) Total Score at Weeks 8 and 12.
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill).
Time Frame	Baseline to Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Week 8 Last Observation Carried Forward: placebo = 152, Bupropion = 160, Week 8 Observed Cases: placebo = 113, Bupropion = 106, Week 12 Last Observation Carried Forward: placebo = 155, Bupropion = 160 Week 12 Observed Cases: placebo = 111, Bupropion = 98

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Week 8 Mean - Last Observation Carried Forward	-21.0 (37.31)	-20.8 (38.87)
Week 8 Mean - Observed Cases	-33.2 (30.51)	-38.2 (28.68)
Week 12 Mean - Last Observation Carried Forward	-26.5 (41.65)	-25.5 (43.05)
Week 12 Mean - Observed Cases	-43.0 (32.51)	-48.4 (29.96)

5. Secondary Outcome

Title	Percentage of Responders Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill). Responders are defined as subjects with 50% or greater reduction from baseline in HAM-D total score.
Time Frame	Baseline to Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Week 8 Last Observation Carried Forward: placebo = 152, Bupropion = 160, Week 8 Observed Cases: placebo = 113, Bupropion = 106, Week 12 Last Observation Carried Forward: placebo = 155, Bupropion = 160, Week 12 Observed Cases: placebo = 111, Bupropion = 98

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Week 8 Mean Last Observation Carried Forward	24	26
Week 8 Mean Observed Cases	31	38
Week 12 Mean Last Observation Carried Forward	37	38
Week 12 Mean Observed Cases	50	59

6. Secondary Outcome

Title	Percentage of Remitters Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAM-D score range from 0 (not ill) to 52 (severely ill). Remitters are defined as subjects with HAM-D total score ≤ 7.
Time Frame	Baseline to Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Week 8 Last Observation Carried Forward: placebo = 152, Bupropion = 160, Week 8 Observed Cases: placebo = 113, Bupropion = 106, Week 12 Last Observation Carried Forward: placebo = 155, Bupropion = 160 Week 12 Observed Cases: placebo = 111, Bupropion = 98

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Week 8 Mean Last Observation Carried Forward	18	18
Week 8 Mean Observed Cases	22	26
Week 12 Mean Last Observation Carried Forward	25	24
Week 12 Mean Observed Cases	33	38

7. Secondary Outcome

Title	Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2, with total HAM-D scores ranging from 0 (not ill) to 54 (severely ill).
Time Frame	Baseline to Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Week 8 Last Observation Carried Forward (LOCF): placebo=152, Bupropion=160; Week 12 LOCF: placebo=155, Bupropion=160. Gastrointestinal, GI.

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Depressed Mood, Week 8 Mean LOCF	-0.5 (1.07)	-0.5 (1.20)
Depressed Mood, Week 12 Mean LOCF	-0.6 (1.17)	-0.6 (1.30)
Feelings of Guilt, Week 8 Mean LOCF	-0.3 (0.91)	-0.3 (0.75)
Feelings of Guilt, Week 12 Mean LOCF	-0.3 (0.90)	-0.4 (0.77)
Suicide, Week 8 Mean LOCF	-0.1 (0.82)	-0.1 (0.73)
Suicide, Week 12 Mean LOCF	-0.1 (0.82)	-0.1 (0.72)
Insomnia Early, Week 8 Mean LOCF	-0.3 (0.83)	-0.3 (0.82)
Insomnia Early, Week 12 Mean LOCF	-0.4 (0.85)	-0.3 (0.89)
Insomnia Middle, Week 8 Mean LOCF	-0.4 (0.87)	-0.3 (0.73)
Insomnia Middle, Week 12 Mean LOCF	-0.4 (0.91)	-0.3 (0.79)
Insomnia Late, Week 8 Mean LOCF	-0.3 (0.87)	-0.3 (0.78)
Insomnia Late, Week 12 Mean LOCF	-0.3 (0.91)	-0.4 (0.88)
Work and Activities, Week 8 Mean LOCF	-0.4 (0.93)	-0.4 (1.18)
Work and Activities, Week 12 Mean LOCF	-0.6 (1.13)	-0.5 (1.35)
Retardation, Week 8 Mean LOCF	-0.2 (0.69)	-0.2 (0.68)
Retardation, Week 12 Mean LOCF	-0.3 (0.78)	-0.3 (0.73)
Agitation, Week 8 Mean LOCF	-0.2 (0.68)	-0.2 (0.77)
Agitation, Week 12 Mean LOCF	-0.3 (0.77)	-0.2 (0.77)
Anxiety Psychic, Week 8 Mean LOCF	-0.3 (1.16)	-0.4 (1.10)
Anxiety Psychic, Week 12 Mean LOCF	-0.5 (1.26)	-0.5 (1.19)
Anxiety Somatic, Week 8 Mean LOCF	-0.2 (0.88)	-0.3 (0.92)
Anxiety Somatic, Week 12 Mean LOCF	-0.3 (0.89)	-0.4 (0.99)
Somatic Symptoms GI, Week 8 Mean LOCF	-0.1 (0.61)	0.0 (0.74)
Somatic Symptoms GI, Week 12 Mean LOCF	-0.1 (0.64)	-0.0 (0.80)
Somatic Symptoms General, Week 8 Mean LOCF	-0.2 (0.65)	-0.2 (0.69)
Somatic Symptoms General, Week 12 Mean LOCF	-0.2 (0.71)	-0.3 (0.71)
Genital Symptoms, Week 8 Mean LOCF	-0.2 (0.58)	-0.2 (0.62)
Genital Symptoms, Week 12 Mean LOCF	-0.2 (0.66)	-0.3 (0.71)
Hypochondriasis, Week 8 Mean LOCF	-0.2 (0.77)	-0.1 (0.84)
Hypochondriasis, Week 12 Mean LOCF	-0.3 (0.78)	-0.2 (0.89)
Loss of Weight by History, Week 8 Mean LOCF	-0.1 (0.60)	-0.0 (0.58)
Loss of Weight by History, Week 12 Mean LOCF	-0.1 (0.63)	0.0 (0.64)
Insight, Week 8 Mean LOCF	-0.1 (0.34)	-0.1 (0.41)
Insight, Week 12 Mean LOCF	-0.1 (0.38)	-0.1 (0.45)

8. Secondary Outcome

Title	Percentage of Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12
Description	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2, with total HAM-D scores ranging from 0 (not ill) to 54 (severely ill).
Time Frame	Baseline to Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Last Observation Carried Forward, LOCF; Gastrointestinal, GI; Somatic, Som.; General, Gen.; Week, W.

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Depressed Mood, Week 8 Mean LOCF, n=152, 158	-17.7 (60.38)	-18.5 (62.38)
Depressed Mood, Week 12 Mean LOCF, n=155, 158	-25.9 (62.78)	-22.2 (68.41)
Feelings of Guilt, Week 8 Mean LOCF, n=128, 131	-24.9 (55.10)	-25.8 (52.83)
Feelings of Guilt, Week 12 Mean LOCF, n=129, 131	-30.7 (56.34)	-30.8 (53.61)
Suicide, Week 8 Mean LOCF, n=79, 75	-34.2 (60.20)	-26.7 (70.87)
Suicide, Week 12 Mean LOCF, n=80, 75	-37.5 (56.53)	-26.0 (74.14)
Insomnia Early, Week 8 Mean LOCF, n=112, 119	-34.8 (53.20)	-29.8 (54.59)
Insomnia Early, Week 12 Mean LOCF, n=114, 119	-42.5 (53.73)	-31.9 (58.49)
Insomnia Middle, Week 8 Mean LOCF, n=119, 124	-42.0 (53.28)	-32.3 (51.48)
Insomnia Middle, Week 12 Mean LOCF, n=122, 124	-48.4 (54.90)	-37.1 (54.43)
Insomnia Late, Week 8 Mean LOCF, n=109, 117	-39.9 (56.43)	-31.6 (54.38)
Insomnia Late, Week 12 Mean LOCF, n=110, 117	-43.2 (61.88)	-37.2 (62.34)
Work and Activities, Week 8 Mean LOCF, n=151, 156	-16.6 (43.93)	-15.3 (55.66)
Work and Activities, Week 12 Mean LOCF, n=154, 156	-23.3 (47.61)	-19.4 (62.51)
Retardation, Week 8 Mean LOCF, n=114, 124	-28.4 (58.70)	-31.0 (53.19)
Retardation, Week 12 Mean LOCF, n=117, 124	-32.5 (63.08)	-38.3 (56.71)
Agitation, Week 8 Mean LOCF, n=87, 99	-38.7 (61.87)	-44.9 (60.40)
Agitation, Week 12 Mean LOCF, n=89, 99	-51.1 (64.83)	-44.9 (63.28)
Anxiety Psychic, Week 8 Mean LOCF, n=146, 151	-14.0 (58.25)	-17.9 (55.14)
Anxiety Psychic, Week 12 Mean LOCF, n=148, 151	-19.1 (62.70)	-21.0 (66.45)
Anxiety Somatic, Week 8 Mean LOCF, n=144, 155	-9.5 (57.89)	-13.9 (60.12)
Anxiety Somatic, Week 12 Mean LOCF, n=147, 155	-13.7 (59.35)	-17.7 (63.07)
Somatic Symptoms GI, Week 8 Mean LOCF, n=95, 93	-30.5 (56.16)	-25.8 (63.68)
Somatic Symptoms GI, Week 12 Mean LOCF, n=97, 93	-23.7 (62.12)	-34.9 (65.02)
Somatic Symptoms Gen., Week 8 Mean LOCF, n=146,152	-13.4 (50.61)	-18.8 (48.08)
Som. Symptoms Gen., Week 12 Mean LOCF, n=149, 152	-15.8 (54.55)	-23.7 (51.13)
Genital Symptoms, Week 8 Mean LOCF, n=115, 129	-15.2 (45.97)	-21.7 (45.86)
Genital Symptoms, Week 12 Mean LOCF, n=118, 129	-16.5 (51.50)	-29.5 (50.24)
Hypochondriasis, Week 8 Mean LOCF, n=93, 102	-34.6 (55.78)	-28.3 (63.70)
Hypochondriasis, Week 12 Mean LOCF, n=95, 102	-38.6 (56.82)	-38.1 (66.27)
Loss of Weight by Hist., W 8 Mean LOCF, n=32, 26	-60.9 (45.32)	-51.9 (57.41)
Loss of Weight by Hist., W 12 Mean LOCF, n=34, 26	-58.8 (48.42)	-57.7 (57.78)
Insight, Week 8 Mean LOCF, n=48, 51	-27.1 (44.91)	-41.2 (49.71)
Insight, Week 12 Mean LOCF, n=49, 51	-36.7 (48.71)	-47.1 (50.41)

9. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions - Severity of Illness (CGI-S) Scale at Weeks 1, 2, 3, 4, and 8 and 12
Description	The 7-point Clinical Global Impressions-Severity of Illness Scale (CGI-S) measures the severity of psychiatric symptoms. The following scores can be given: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill patients.
Time Frame	Baseline to Weeks 1, 2, 3, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Week 1 Mean LOCF, n=157, 165	-0.0 (0.45)	0.0 (0.51)
Week 1 Mean OC, n=139, 143	-0.1 (0.40)	-0.0 (0.45)
Week 2 Mean LOCF, n=157, 165	-0.1 (0.63)	-0.1 (0.71)
Week 2 Mean OC, n=134, 132	-0.2 (0.59)	-0.3 (0.66)
Week 3 Mean LOCF, n=157, 165	-0.2 (0.71)	-0.2 (0.73)
Week 3 Mean OC, n=130, 127	-0.3 (0.61)	-0.4 (0.65)
Week 4 Mean LOCF, n=157, 165	-0.2 (0.76)	-0.2 (0.83)
Week 4 Mean OC, n=127, 116	-0.4 (0.65)	-0.4 (0.77)
Week 8 Mean LOCF, n=157, 164	-0.5 (1.02)	-0.5 (1.01)
Week 8 Mean OC, n=113, 106	-0.7 (0.87)	-0.9 (0.85)
Week 12 Mean LOCF, n=157, 163	-0.6 (1.12)	-0.6 (1.15)
Week 12 Mean OC, n=111, 98	-0.9 (0.90)	-1.1 (0.98)

10. Secondary Outcome

Title	Percentage of Responders Based on the Clinical Global Impression - Global Improvement (CGI-I) Scale at Weeks 8 and 12
Description	The CGI-I assesses the investigator's impression of the patient's current illness. The time span is the week before the rating and the score ranges from 1 (very much improved) to 7 (very much worse). Responders are subjects that have a score of 1 (very much improved) or 2 (much improved) on the CGI-I.
Time Frame	Baseline to Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis set. Week 8 Last Observation Carried Forward: placebo = 153, Bupropion = 159; Week 8 Observed Cases: placebo = 113, Bupropion = 106; Week 12 Last Observation Carried Forward: placebo = 156, Bupropion = 158; Week 12 Observed Cases: placebo = 111, Bupropion = 98

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Week 8 Mean Last Observation Carried Forward	33	38
Week 8 Mean Observed Cases	42	57
Week 12 Mean Last Observation Carried Forward	44	48
Week 12 Mean Observed Cases	57	73

11. Secondary Outcome

Title	Study Continuation Rate as Assessed by the Number of Participants at Risk at Week 12
Description	Kaplan-Meier estimates were calculated using event or censoring and time to event or censoring. Participants at risk refers to participants with either a censoring or event time beyond the time point of interest (Week 12).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set. Participants at risk refers to participants with either a censoring or event time beyond the time point of interest (Week 12).

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	157	165
Participants at risk	102 65%	90 54.5%
Participants not at risk	55 35%	75 45.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bupropion SR
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	Log Rank
	Comments

12. Secondary Outcome

Title	Safety: Adverse Events by Organ System Class, Intensity, and Frequency
Description	Assessment of intensity was based on investigators/subinvestigator's clinical judgement per protocol instructions: Mild event, easily tolerated, with minimal discomfort and not interfering with Activities of Daily Living (ADLs); moderate event, with discomfort that interferes with ADLs; severe event, prevents ADLs.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Safety population: comprised of participants who took at least one dose of the treatment period investigational product. The number of participants analyzed for this outcome measure represents the total number of events at each intensity.

Arm/Group Title	Placebo	Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.	Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
Measure Participants	159	166
Nervous System Disorders (NSD) - Any Event, mild	32	31
NSD - Any Event, moderate	8	16
NSD - Any Event, severe	1	3
NSD - Dizziness, mild	11	8
NSD - Dizziness, moderate	4	8
NSD - Dizziness, severe	1	0
NSD - Headache, mild	6	8
NSD - Headache, moderate	3	6
NSD - Headache, severe	0	1
NSD - Somnolence, mild	10	8
NSD - Somnolence, moderate	0	0
NSD - Somnolence, severe	0	0
NSD - Hypoesthesia, mild	5	1
NSD - Hypoesthesia, moderate	1	0
NSD - Hypoesthesia, severe	0	0
NSD - Dysgeusia, mild	0	4
NSD - Dysgeusia, moderate	0	1
NSD - Dysgeusia, severe	0	0
NSD - Depressed Level of Consciousness, mild	0	1
NSD - Depressed Level of Consciousness, moderate	0	2
NSD - Depressed Level of Consciousness, severe	0	1
NSD - Tremor, mild	0	4
NSD - Tremor, moderate	0	0
NSD - Tremor, severe	0	0
NSD - Convulsion, mild	0	0
NSD - Convulsion, moderate	0	1
NSD - Convulsion, severe	0	1
NSD - Dizziness postural, mild	0	1
NSD - Dizziness postural, moderate	1	0
NSD - Dizziness postural, severe	0	0
NSD - Dysesthesia, mild	0	0
NSD - Dysesthesia, moderate	1	1
NSD - Dysesthesia, severe	0	0
NSD - Parosmia, mild	2	0
NSD - Parosmia, moderate	0	0
NSD - Parosmia, severe	0	0
NSD - Akathisia, mild	0	0
NSD - Akathisia, moderate	1	0
NSD - Akathisia, severe	0	0
NSD - Anterograde Amnesia, mild	1	0
NSD - Anterograde Amnesia, moderate	0	0
NSD - Anterograde Amnesia, severe	0	0
NSD - Dysarthria, mild	1	0
NSD - Dysarthria, moderate	0	0
NSD - Dysarthria, severe	0	0
NSD - Head discomfort, mild	1	0
NSD - Head discomfort, moderate	0	0
NSD - Head discomfort, severe	0	0
NSD - Hyperesthesia, mild	0	1
NSD - Hyperesthesia, moderate	0	0
NSD - Hyperesthesia, severe	0	0
NSD - Loss of consciousness, mild	0	1
NSD - Loss of consciousness, moderate	0	0
NSD - Loss of consciousness, severe	0	0
NSD - Paraesthesia, mild	0	1
NSD - Paraesthesia, moderate	0	0
NSD - Paraesthesia, severe	0	0
Gastrointestinal Disorders (GID)-Any Event, mild	28	32
GID - Any Event, moderate	15	14
GID - Any Event, severe	1	0
GID - Nausea, mild	12	16
GID - Nausea, moderate	8	10
GID - Nausea, severe	1	0
GID - Diarrhea, mild	6	6
GID - Diarrhea, moderate	3	1
GID - Diarrhea, severe	0	0
GID - Vomiting, mild	4	5
GID - Vomiting, moderate	4	2
GID - Vomiting, severe	0	0
GID - Abdominal Pain upper, mild	0	3
GID - Abdominal Pain upper, moderate	1	2
GID - Abdominal Pain upper, severe	0	0
GID - Stomach Discomfort, mild	2	3
GID - Stomach Discomfort, moderate	1	0
GID - Stomach Discomfort, severe	0	0
GID - Constipation, mild	5	0
GID - Constipation, moderate	0	0
GID - Constipation, severe	0	0
GID - Abdominal Pain, mild	1	3
GID - Abdominal Pain, moderate	0	0
GID - Abdominal Pain, severe	0	0
GID - Stomatitis, mild	1	2
GID - Stomatitis, moderate	0	1
GID - Stomatitis, severe	0	0
GID - Toothache, mild	2	0
GID - Toothache, moderate	1	0
GID - Toothache, severe	0	0
GID - Abdominal Distension, mild	0	2
GID - Abdominal Distension, moderate	0	0
GID - Abdominal Distension, severe	0	0
GID - Gastritis, mild	1	1
GID - Gastritis, moderate	0	0
GID - Gastritis, severe	0	0
GID - Hypoesthesia oral, mild	1	1
GID - Hypoesthesia oral, moderate	0	0
GID - Hypoesthesia oral, severe	0	0
GID - Melaena, mild	1	1
GID - Melaena, moderate	0	0
GID - Melaena, severe	0	0
GID - Abdominal Pain Lower, mild	0	0
GID - Abdominal Pain Lower, moderate	0	1
GID - Abdominal Pain Lower, severe	0	0
GID - Dyspepsia, mild	0	0
GID - Dyspepsia, moderate	1	0
GID - Dyspepsia, severe	0	0
GID - Gingival Swelling, mild	1	0
GID - Gingival Swelling, moderate	0	0
GID - Gingival Swelling, severe	0	0
Infections and Infestations (INF)-Any Event, mild	38	30
INF - Any Event, moderate	3	4
INF - Any Event, severe	0	0
INF - Nasopharyngitis, mild	31	24
INF - Nasopharyngitis, moderate	0	4
INF - Nasopharyngitis, severe	0	0
INF - Gastrointestinal infection, mild	3	3
INF - Gastrointestinal infection, moderate	0	0
INF - Gastrointestinal infection, severe	0	0
INF - Bronchitis acute, mild	0	3
INF - Bronchitis acute, moderate	0	0
INF - Bronchitis acute, severe	0	0
INF - Bronchitis, mild	1	0
INF - Bronchitis, moderate	1	0
INF - Bronchitis, severe	0	0
INF - Gastroenteritis, mild	1	0
INF - Gastroenteritis, moderate	1	0
INF - Gastroenteritis, severe	0	0
INF - Enteritis Infectious, mild	1	0
INF - Enteritis Infectious, moderate	0	0
INF - Enteritis Infectious, severe	0	0
INF - Gastroenteritis viral, mild	0	0
INF - Gastroenteritis viral, moderate	1	0
INF - Gastroenteritis viral, severe	0	0
INF - Otitis Externa, mild	1	0
INF - Otitis Externa, moderate	0	0
INF - Otitis Externa, severe	0	0
INF - Purulence, mild	1	0
INF - Purulence, moderate	0	0
INF - Purulence, severe	0	0
INF - Rhinitis, mild	0	1
INF - Rhinitis, moderate	0	0
INF - Rhinitis, severe	0	0
INF - Vaginal Candidiasis, mild	1	0
INF - Vaginal Candidiasis, moderate	0	0
INF - Vaginal Candidiasis, severe	0	0
Psychiatric Disorders (PsyDO) - Any Event, mild	8	10
PsyDO - Any Event, moderate	13	14
PsyDO - Any Event, severe	7	5
PsyDO - Depression, mild	2	2
PsyDO - Depression, moderate	11	9
PsyDO - Depression, severe	7	3
PsyDO - Insomnia, mild	0	4
PsyDO - Insomnia, moderate	1	1
PsyDO - Insomnia, severe	0	0
PsyDO - Mood altered, mild	3	2
PsyDO - Mood altered, moderate	0	1
PsyDO - Mood altered, severe	0	0
PsyDO - Mania, mild	0	0
PsyDO - Mania, moderate	1	0
PsyDO - Mania, severe	0	1
PsyDO - Anxiety, mild	1	0
PsyDO - Anxiety, moderate	0	0
PsyDO - Anxiety, severe	0	0
PsyDO - Bipolar Disorder, mild	0	0
PsyDO - Bipolar Disorder, moderate	0	0
PsyDO - Bipolar Disorder, severe	0	1
PsyDO - Bruxism, mild	0	1
PsyDO - Bruxism, moderate	0	0
PsyDO - Bruxism, severe	0	0
PsyDO - Delerium, mild	0	1
PsyDO - Delerium, moderate	0	0
PsyDO - Delerium, severe	0	0
PsyDO - Depression suicidal, mild	0	0
PsyDO - Depression suicidal, moderate	0	1
PsyDO - Depression suicidal, severe	0	0
PsyDO - Dysphoria, mild	0	1
PsyDO - Dysphoria, moderate	0	0
PsyDO - Dysphoria, severe	0	0
PsyDO - Early morning awakening, mild	0	0
PsyDO - Early morning awakening, moderate	0	1
PsyDO - Early morning awakening, severe	0	0
PsyDO - Hallucination, mild	0	1
PsyDO - Hallucination, moderate	0	0
PsyDO - Hallucination, severe	0	0
PsyDO - Hypomania, mild	1	0
PsyDO - Hypomania, moderate	0	0
PsyDO - Hypomania, severe	0	0
PsyDO - Intentional self-injury, mild	1	0
PsyDO - Intentional self-injury, moderate	0	0
PsyDO - Intentional self-injury, severe	0	0
PsyDO - Libido decreased, mild	1	0
PsyDO - Libido decreased, moderate	0	0
PsyDO - Libido decreased, severe	0	0
PsyDO - Nightmare, mild	0	0
PsyDO - Nightmare, moderate	0	1
PsyDO - Nightmare, severe	0	0
General Disorders (GD) - Any Event, mild	10	16
GD - Any Event, moderate	5	5
GD - Any Event, severe	0	0
GD - Drug Withdrawal Syndrome, mild	2	6
GD - Drug Withdrawal Syndrome, moderate	2	3
GD - Drug Withdrawal Syndrome, severe	0	0
GD - Thirst, mild	4	9
GD - Thirst, moderate	0	0
GD - Thirst, severe	0	0
GD - Malaise, mild	1	1
GD - Malaise, moderate	2	0
GD - Malaise, severe	0	0
GD - Feeling abnormal, mild	0	1
GD - Feeling abnormal, moderate	0	1
GD - Feeling abnormal, severe	0	0
GD - Irritability, mild	0	0
GD - Irritability, moderate	1	1
GD - Irritability, severe	0	0
GD - Chills, mild	1	0
GD - Chills, moderate	0	0
GD - Chills, severe	0	0
GD - Edema, mild	1	0
GD - Edema, moderate	0	0
GD - Edema, severe	0	0
GD - Edema peripheral, mild	1	0
GD - Edema peripheral, moderate	0	0
GD - Edema peripheral, severe	0	0
GD - Pain, mild	1	0
GD - Pain, moderate	0	0
GD - Pain, severe	0	0
Skin & tissue disorders (SDO) - Any Event, mild	6	8
SDO - Any Event, moderate	1	6
SDO - Any Event, severe	0	1
SDO - Urticaria, mild	0	1
SDO - Urticaria, moderate	0	4
SDO - Urticaria, severe	0	0
SDO - Rash, mild	1	2
SDO - Rash, moderate	0	1
SDO - Rash, severe	0	0
SDO - Eczema, mild	1	1
SDO - Eczema, moderate	0	0
SDO - Eczema, severe	0	0
SDO - Hyperhidrosis, mild	2	0
SDO - Hyperhidrosis, moderate	0	0
SDO - Hyperhidrosis, severe	0	0
SDO - Hypoesthesia facial, mild	0	2
SDO - Hypoesthesia facial, moderate	0	0
SDO - Hypoesthesia facial, severe	0	0
SDO - Pruritus generalised, mild	0	1
SDO - Pruritus generalised, moderate	0	1
SDO - Pruritus generalised, severe	0	0
SDO - Alopecia, mild	0	0
SDO - Alopecia, moderate	0	1
SDO - Alopecia, severe	0	0
SDO - Alopecia areata, mild	0	1
SDO - Alopecia areata, moderate	0	0
SDO - Alopecia areata, severe	0	0
SDO - Dermatitis Contact, mild	0	0
SDO - Dermatitis Contact, moderate	1	0
SDO - Dermatitis Contact, severe	0	0
SDO - Erythema, mild	1	0
SDO - Erythema, moderate	0	0
SDO - Erythema, severe	0	0
SDO - Hemorrhage subcutaneous, mild	0	0
SDO - Hemorrhage subcutaneous, moderate	0	0
SDO - Hemorrhage subcutaneous, severe	0	1
SDO - Hyperkeratosis, mild	0	1
SDO - Hyperkeratosis, moderate	0	0
SDO - Hyperkeratosis, severe	0	0
SDO - Pigmentation disorder, mild	1	0
SDO - Pigmentation disorder, moderate	0	0
SDO - Pigmentation disorder, severe	0	0
SDO - Sweat Gland Disorder, mild	0	1
SDO - Sweat Gland Disorder, moderate	0	0
SDO - Sweat Gland Disorder, severe	0	0
Investigations (INV) - Any Event, mild	5	10
INV - Any Event, moderate	1	2
INV - Any Event, severe	0	0
INV - Alanine Aminotransferase increased, mild	3	4
INV - Alanine Aminotransferase increased, moderate	0	0
INV - Alanine Aminotransferase increased, severe	0	0
INV - Weight decreased, mild	0	3
INV - Weight decreased, moderate	0	0
INV - Weight decreased, severe	0	0
INV - Aspartate Aminotransferase increased, mild	0	2
INV-Aspartate Aminotransferase increased, moderate	0	0
INV - Aspartate Aminotransferase increased, severe	0	0
INV - Blood Bilirubin increased, mild	1	1
INV - Blood Bilirubin increased, moderate	0	0
INV - Blood Bilirubin increased, severe	0	0
INV - Glucose urine present, mild	0	1
INV - Glucose urine present, moderate	0	1
INV - Glucose urine present, severe	0	0
INV - Protein urine present, mild	0	2
INV - Protein urine present, moderate	0	0
INV - Protein urine present, severe	0	0
INV - White Blood Cell Count decreased, mild	0	1
INV - White Blood Cell Count decreased, moderate	0	1
INV - White Blood Cell Count decreased, severe	0	0
INV - Blood pressure decreased, mild	0	0
INV - Blood pressure decreased, moderate	1	0
INV - Blood pressure decreased, severe	0	0
INV - Electrocardiogram T wave inversion, mild	1	0
INV - Electrocardiogram T wave inversion, moderate	0	0
INV - Electrocardiogram T wave inversion, severe	0	0
INV - Hematocrit decreased, mild	0	1
INV - Hematocrit decreased, moderate	0	0
INV - Hematocrit decreased, severe	0	0
INV - Hemoglobin decreased, mild	0	1
INV - Hemoglobin decreased, moderate	0	0
INV - Hemoglobin decreased, severe	0	0
INV - Red Blood Cell Count decreased, mild	0	1
INV - Red Blood Cell Count decreased, moderate	0	0
INV - Red Blood Cell Count decreased, severe	0	0
Musculoskeletal Disorders (MD) - Any Event, mild	9	6
MD - Any Event, moderate	0	2
MD - Any Event, severe	0	0
MD - Back Pain, mild	1	1
MD - Back Pain, moderate	0	2
MD - Back Pain, severe	0	0
MD - Musculoskeletal stiffness, mild	3	1
MD - Musculoskeletal stiffness, moderate	0	0
MD - Musculoskeletal stiffness, severe	0	0
MD - Myalgia, mild	2	1
MD - Myalgia, moderate	0	0
MD - Myalgia, severe	0	0
MD - Neck Pain, mild	0	2
MD - Neck Pain, moderate	0	0
MD - Neck Pain, severe	0	0
MD - Pain in extremity, mild	2	0
MD - Pain in extremity, moderate	0	0
MD - Pain in extremity, severe	0	0
MD - Arthralgia, mild	0	1
MD - Arthralgia, moderate	0	0
MD - Arthralgia, severe	0	0
MD - Fasciitis, mild	1	0
MD - Fasciitis, moderate	0	0
MD - Fasciitis, severe	0	0
Respiratory Disorders (RTM) - Any Event, mild	4	6
RTM -Any Event, moderate	0	3
RTM -Any Event, severe	0	0
RTM - Upper respiratory Tract inflammation, mild	3	3
RTM-Upp. respiratory Tract inflammation, moderate	0	1
RTM-Upp. respiratory Tract inflammation, severe	0	0
RTM - Asthma, mild	0	2
RTM - Asthma, moderate	0	1
RTM - Asthma, severe	0	0
RTM - Cough, mild	0	1
RTM - Cough, moderate	0	1
RTM - Cough, severe	0	0
RTM - Pharyngolaryngeal Pain, mild	1	0
RTM - Pharyngolaryngeal Pain, moderate	0	0
RTM - Pharyngolaryngeal Pain, severe	0	0
Injury and complications (IPPC) - Any Event, mild	2	2
IPPC - Any Event, moderate	1	3
IPPC - Any Event, severe	0	0
IPPC - Contusion, mild	0	2
IPPC - Contusion, moderate	0	0
IPPC - Contusion, severe	0	0
IPPC - Intentional Overdose, mild	1	0
IPPC - Intentional Overdose, moderate	0	1
IPPC - Intentional Overdose, severe	0	0
IPPC - Head Injury, mild	0	0
IPPC - Head Injury, moderate	0	1
IPPC - Head Injury, severe	0	0
IPPC - Joint sprain, mild	0	1
IPPC - Joint sprain, moderate	0	0
IPPC - Joint sprain, severe	0	0
IPPC - Rib fracture, mild	0	0
IPPC - Rib fracture, moderate	1	0
IPPC - Rib fracture, severe	0	0
IPPC - Thermal Burn, mild	0	0
IPPC - Thermal Burn, moderate	0	1
IPPC - Thermal Burn, severe	0	0
IPPC - Wound, mild	1	0
IPPC - Wound, moderate	0	0
IPPC - Wound, severe	0	0
Ear Disorders (ED) - Any Event, mild	3	2
ED - Any Event, moderate	0	0
ED - Any Event, severe	0	0
ED - Tinnitus, mild	2	2
ED - Tinnitus, moderate	0	0
ED - Tinnitus, severe	0	0
ED - Ear Discomfort, mild	1	0
ED - Ear Discomfort, moderate	0	0
ED - Ear Discomfort, severe	0	0
Eye Disorders (EyeDO) - Any Event, mild	0	1
EyeDO - Any Event, moderate	0	3
EyeDO - Any Event, severe	0	0
EyeDO - Chalazion, mild	0	0
EyeDO - Chalazion, moderate	0	2
EyeDO - Chalazion, severe	0	0
EyeDO - Abnormal sensations in eye, mild	0	0
EyeDO - Abnormal sensations in eye, moderate	0	1
EyeDO - Abnormal sensations in eye, severe	0	0
EyeDO - Conjunctival haemorrhage, mild	0	1
EyeDO - Conjunctival haemorrhage, moderate	0	0
EyeDO - Conjunctival haemorrhage, severe	0	0
Metabolism Disorders (MetDO) - Any Event, mild	2	1
MetDO - Any Event, moderate	1	0
MetDO - Any Event, severe	0	0
MetDO - Anorexia, mild	0	1
MetDO - Anorexia, moderate	1	0
MetDO - Anorexia, severe	0	0
MetDO - Dehydration, mild	2	0
MetDO - Dehydration, moderate	0	0
MetDO - Dehydration, severe	0	0
MetDO - Hyperlipidemia, mild	1	0
MetDO - Hyperlipidemia, moderate	0	0
MetDO - Hyperlipidemia, severe	0	0
MetDO - Hypovitaminosis, mild	1	0
MetDO - Hypovitaminosis, moderate	0	0
MetDO - Hypovitaminosis, severe	0	0
Vascular Disorders (VD) - Any Event, mild	2	2
VD - Any Event, moderate	0	0
VD - Any Event, severe	0	0
VD - Hot Flush, mild	1	2
VD - Hot Flush, moderate	0	0
VD - Hot Flush, severe	0	0
VD - Hypertension, mild	1	0
VD - Hypertension, moderate	0	0
VD - Hypertension, severe	0	0
Blood & Lymph Disorders (BLD) - Any Event, mild	0	2
BLD - Any Event, moderate	0	1
BLD - Any Event, severe	0	0
BLD - Anemia, mild	0	1
BLD - Anemia, moderate	0	1
BLD - Anemia, severe	0	0
BLD - Lymphadenopathy, mild	0	1
BLD - Lymphadenopathy, moderate	0	0
BLD - Lymphadenopathy, severe	0	0
Hepatobiliary disorders (HD) - Any Event, mild	1	1
HD - Any Event, moderate	0	1
HD - Any Event, severe	0	0
HD - Hepatic Function abnormal, mild	1	1
HD - Hepatic Function abnormal, moderate	0	1
HD - Hepatic Function abnormal, severe	0	0
Reproductive Disorders (RBD) - Any Event, mild	0	1
RBD - Any Event, moderate	0	1
RBD - Any Event, severe	0	1
RBD - Galactorrhea, mild	0	0
RBD - Galactorrhea, moderate	0	1
RBD - Galactorrhea, severe	0	0
RBD - Menometrorrhagia, mild	0	1
RBD - Menometrorrhagia, moderate	0	0
RBD - Menometrorrhagia, severe	0	0
RBD - Premenstrual Syndrome, mild	0	0
RBD - Premenstrual Syndrome, moderate	0	0
RBD - Premenstrual Syndrome, severe	0	1
Cardiac Disorders (CD) - Any Event, mild	1	1
CD - Any Event, moderate	0	0
CD - Any Event, severe	0	0
CD - Palpitations, mild	1	1
CD - Palpitations, moderate	0	0
CD - Palpitations, severe	0	0
Renal & Urinary Disorders (RUD) - Any Event, mild	0	2
RUD - Any Event, moderate	0	0
RUD - Any Event, severe	0	0
RUD - Dysuria, mild	0	1
RUD - Dysuria, moderate	0	0
RUD - Dysuria, severe	0	0
RUD - Pollakiuria, mild	0	1
RUD - Pollakiuria, moderate	0	0
RUD - Pollakiuria, severe	0	0
Endocrine Disorders (ENDO) - Any Event, mild	0	1
ENDO - Any Event, moderate	0	0
ENDO - Any Event, severe	0	0
ENDO - Hyperprolactinaemia, mild	0	1
ENDO - Hyperprolactinaemia, moderate	0	0
ENDO - Hyperprolactinaemia, severe	0	0

Adverse Events

Arm/Group Title	Placebo		Bupropion SR
Arm/Group Description	Subjects with Major Depressive Disorder who were randomized to placebo to match Bupropion SR during the treatment period.		Subjects with Major Depressive Disorder who were randomized to take 100 mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100 mg dose of Bupropion morning and evening. Weeks 3 through 12 received 150 mg dose morning and evening. Week 1 = dose level 1, 100 mg. Week 2 = dose level 2, 200 mg. Weeks 3 - 12 = dose level 3, 300 mg.
All Cause Mortality
	Placebo		Bupropion SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Bupropion SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/ (NaN)		5/ (NaN)
Nervous system disorders
Depressed level of Consciousness	0/159 (0%)		2/166 (1.2%)
Convulsion	0/159 (0%)		1/166 (0.6%)
Psychiatric disorders
Bipolar Disorder	0/159 (0%)		1/166 (0.6%)
Mania	0/159 (0%)		1/166 (0.6%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/159 (0%)		1/166 (0.6%)
Other (Not Including Serious) Adverse Events
	Placebo		Bupropion SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/159 (78%)		125/166 (75.3%)
Gastrointestinal disorders
Nausea	21/159 (13.2%)		26/166 (15.7%)
Diarrhea	9/159 (5.7%)		7/166 (4.2%)
Vomiting	8/159 (5%)		7/166 (4.2%)
General disorders
Drug Withdrawal syndrome	4/159 (2.5%)		9/166 (5.4%)
Thirst	4/159 (2.5%)		9/166 (5.4%)
Infections and infestations
Nasopharyngitis	31/159 (19.5%)		28/166 (16.9%)
Nervous system disorders
Dizziness	16/159 (10.1%)		16/166 (9.6%)
Headache	9/159 (5.7%)		15/166 (9%)
Psychiatric disorders
Depression	20/159 (12.6%)		14/166 (8.4%)
Somnolence	10/159 (6.3%)		8/166 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the Publication of results from all centers of a multi-center trial but requests that reports based on Single-site data not precede the primary publication of the entire clinical trial.