Trial Outcomes & Findings for A Study Comparing Duloxetine and Placebo in Assessing Energy and Vitality in Major Depressive Disorder (MDD) Patients (NCT NCT00536471)

Last Updated: 2009-11-20

Results Overview

Item 7 of the HAMD-24 assesses loss of interest or pleasure in work and activities and is an essential symptom in MDD. Scores range from 0 (no difficulty/no loss) to 4 (difficulty/loss).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

776 participants

Primary outcome timeframe

baseline, 8 weeks

Results posted on

2009-11-20

Participant Flow

Study HMFS comprises two identical trials (identified as Group A and Group B). Study Period I was a screening period. Study Period II was a 9-month double-blind treatment period. Study Period III was an optional double-blind 2-week discontinuation/taper period.

Participant milestones

Participant milestones
Measure	Group A - Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Overall Study STARTED	257	127	261	131
Overall Study COMPLETED	101	43	122	57
Overall Study NOT COMPLETED	156	84	139	74

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A - Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Overall Study Lost to Follow-up	48	23	48	22
Overall Study Adverse Event	32	16	28	13
Overall Study Withdrawal by Subject	40	24	43	21
Overall Study Lack of Efficacy	17	18	11	9
Overall Study Protocol Violation	8	1	2	3
Overall Study Physician Decision	11	1	3	2
Overall Study Death	0	0	1	2
Overall Study Sponsor Decision	0	1	3	2

Baseline Characteristics

A Study Comparing Duloxetine and Placebo in Assessing Energy and Vitality in Major Depressive Disorder (MDD) Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A - Duloxetine n=257 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=127 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=261 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=131 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Total n=776 Participants Total of all reporting groups
Age Continuous	42.2 years STANDARD_DEVIATION 12.2 • n=5 Participants	43.7 years STANDARD_DEVIATION 12.5 • n=7 Participants	44.7 years STANDARD_DEVIATION 12.2 • n=5 Participants	43.9 years STANDARD_DEVIATION 11.9 • n=4 Participants	43.6 years STANDARD_DEVIATION 12.2 • n=21 Participants
Sex: Female, Male Female	155 Participants n=5 Participants	78 Participants n=7 Participants	169 Participants n=5 Participants	87 Participants n=4 Participants	489 Participants n=21 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	49 Participants n=7 Participants	92 Participants n=5 Participants	44 Participants n=4 Participants	287 Participants n=21 Participants
Region of Enrollment United States	249 participants n=5 Participants	123 participants n=7 Participants	222 participants n=5 Participants	110 participants n=4 Participants	704 participants n=21 Participants
Region of Enrollment Puerto Rico	8 participants n=5 Participants	4 participants n=7 Participants	39 participants n=5 Participants	21 participants n=4 Participants	72 participants n=21 Participants
History - Atypical Depression Yes	7 participants n=5 Participants	5 participants n=7 Participants	19 participants n=5 Participants	7 participants n=4 Participants	38 participants n=21 Participants
History - Atypical Depression No	250 participants n=5 Participants	122 participants n=7 Participants	242 participants n=5 Participants	124 participants n=4 Participants	738 participants n=21 Participants
History - Melancholic Depression Yes	134 participants n=5 Participants	71 participants n=7 Participants	147 participants n=5 Participants	71 participants n=4 Participants	423 participants n=21 Participants
History - Melancholic Depression No	123 participants n=5 Participants	56 participants n=7 Participants	114 participants n=5 Participants	60 participants n=4 Participants	353 participants n=21 Participants
History - Seasonal Pattern in Major Depressive Disorder (MDD) if ≥3 Previous MDD Episodes Yes	3 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants	4 participants n=4 Participants	19 participants n=21 Participants
History - Seasonal Pattern in Major Depressive Disorder (MDD) if ≥3 Previous MDD Episodes No	220 participants n=5 Participants	105 participants n=7 Participants	232 participants n=5 Participants	112 participants n=4 Participants	669 participants n=21 Participants
History - Seasonal Pattern in Major Depressive Disorder (MDD) if ≥3 Previous MDD Episodes Missing Response	34 participants n=5 Participants	19 participants n=7 Participants	20 participants n=5 Participants	15 participants n=4 Participants	88 participants n=21 Participants
Race/Ethnicity African	63 participants n=5 Participants	36 participants n=7 Participants	30 participants n=5 Participants	16 participants n=4 Participants	145 participants n=21 Participants
Race/Ethnicity Caucasian	160 participants n=5 Participants	73 participants n=7 Participants	172 participants n=5 Participants	81 participants n=4 Participants	486 participants n=21 Participants
Race/Ethnicity Hispanic	29 participants n=5 Participants	11 participants n=7 Participants	55 participants n=5 Participants	30 participants n=4 Participants	125 participants n=21 Participants
Race/Ethnicity East Asian	3 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	1 participants n=4 Participants	12 participants n=21 Participants
Race/Ethnicity West Asian (Indian sub-continent)	2 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants	7 participants n=21 Participants
Race/Ethnicity Native American	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Body Height	168.1 centimeters STANDARD_DEVIATION 10.1 • n=5 Participants	168.5 centimeters STANDARD_DEVIATION 9.2 • n=7 Participants	169.0 centimeters STANDARD_DEVIATION 9.7 • n=5 Participants	168.8 centimeters STANDARD_DEVIATION 9.4 • n=4 Participants	168.6 centimeters STANDARD_DEVIATION 9.7 • n=21 Participants
Body Weight	88.8 kilograms STANDARD_DEVIATION 23.7 • n=5 Participants	84.9 kilograms STANDARD_DEVIATION 22.5 • n=7 Participants	88.6 kilograms STANDARD_DEVIATION 26.6 • n=5 Participants	86.4 kilograms STANDARD_DEVIATION 23.5 • n=4 Participants	87.7 kilograms STANDARD_DEVIATION 24.5 • n=21 Participants
Evaluation - Brief Profile of Mood States (BPOMS) Total Score	49.0 units on a scale STANDARD_DEVIATION 19.2 • n=5 Participants	47.5 units on a scale STANDARD_DEVIATION 18.7 • n=7 Participants	51.8 units on a scale STANDARD_DEVIATION 19.3 • n=5 Participants	51.8 units on a scale STANDARD_DEVIATION 18.7 • n=4 Participants	50.2 units on a scale STANDARD_DEVIATION 19.1 • n=21 Participants
Evaluation - Brief Profile of Mood States (BPOMS) Tension-Anxiety Score	9.5 units on a scale STANDARD_DEVIATION 4.6 • n=5 Participants	9.2 units on a scale STANDARD_DEVIATION 4.6 • n=7 Participants	10.0 units on a scale STANDARD_DEVIATION 5.0 • n=5 Participants	10.4 units on a scale STANDARD_DEVIATION 4.6 • n=4 Participants	9.8 units on a scale STANDARD_DEVIATION 4.7 • n=21 Participants
Evaluation - Brief Profile of Mood States (BPOMS) Depression-Dejection Score	11.8 units on a scale STANDARD_DEVIATION 4.8 • n=5 Participants	11.5 units on a scale STANDARD_DEVIATION 4.8 • n=7 Participants	12.3 units on a scale STANDARD_DEVIATION 4.6 • n=5 Participants	12.0 units on a scale STANDARD_DEVIATION 4.2 • n=4 Participants	12.0 units on a scale STANDARD_DEVIATION 4.7 • n=21 Participants
Evaluation - Brief Profile of Mood States (BPOMS) Anger-Hostility Score	8.9 units on a scale STANDARD_DEVIATION 5.4 • n=5 Participants	9.0 units on a scale STANDARD_DEVIATION 5.4 • n=7 Participants	9.5 units on a scale STANDARD_DEVIATION 5.1 • n=5 Participants	9.5 units on a scale STANDARD_DEVIATION 5.4 • n=4 Participants	9.2 units on a scale STANDARD_DEVIATION 5.3 • n=21 Participants
Evaluation - Brief Profile of Mood States (BPOMS) Vigor-Activity Score	3.4 units on a scale STANDARD_DEVIATION 3.1 • n=5 Participants	3.9 units on a scale STANDARD_DEVIATION 3.1 • n=7 Participants	3.6 units on a scale STANDARD_DEVIATION 3.5 • n=5 Participants	3.4 units on a scale STANDARD_DEVIATION 3.0 • n=4 Participants	3.5 units on a scale STANDARD_DEVIATION 3.2 • n=21 Participants
Evaluation - Brief Profile of Mood States (BPOMS) Fatigue-Inertia Score	12.8 units on a scale STANDARD_DEVIATION 4.6 • n=5 Participants	12.3 units on a scale STANDARD_DEVIATION 4.8 • n=7 Participants	13.5 units on a scale STANDARD_DEVIATION 4.7 • n=5 Participants	13.2 units on a scale STANDARD_DEVIATION 4.5 • n=4 Participants	13.0 units on a scale STANDARD_DEVIATION 4.7 • n=21 Participants
Evaluation - Brief Profile of Mood States (BPOMS) Confusion-Bewilderment Score	9.7 units on a scale STANDARD_DEVIATION 4.0 • n=5 Participants	9.6 units on a scale STANDARD_DEVIATION 3.9 • n=7 Participants	9.8 units on a scale STANDARD_DEVIATION 4.1 • n=5 Participants	10.1 units on a scale STANDARD_DEVIATION 3.8 • n=4 Participants	9.8 units on a scale STANDARD_DEVIATION 4.0 • n=21 Participants
Evaluation - 16-Item Quick Inventory of Depressive Symptomatology (QIDS16) Total Score	14.7 units on a scale STANDARD_DEVIATION 4.1 • n=5 Participants	13.7 units on a scale STANDARD_DEVIATION 4.4 • n=7 Participants	15.0 units on a scale STANDARD_DEVIATION 4.4 • n=5 Participants	14.7 units on a scale STANDARD_DEVIATION 3.8 • n=4 Participants	14.6 units on a scale STANDARD_DEVIATION 4.2 • n=21 Participants
Evaluation - 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score	22.9 units on a scale STANDARD_DEVIATION 4.3 • n=5 Participants	22.8 units on a scale STANDARD_DEVIATION 3.7 • n=7 Participants	22.8 units on a scale STANDARD_DEVIATION 4.5 • n=5 Participants	22.9 units on a scale STANDARD_DEVIATION 4.9 • n=4 Participants	22.8 units on a scale STANDARD_DEVIATION 4.4 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 10:Anxiety (Psychic)	2.1 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	2.1 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	2.1 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	2.2 units on a scale STANDARD_DEVIATION 0.8 • n=4 Participants	2.1 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 11:Anxiety (Somatic)	1.4 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.5 units on a scale STANDARD_DEVIATION 0.8 • n=7 Participants	1.6 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants	1.6 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	1.5 units on a scale STANDARD_DEVIATION 0.9 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 13:Somatic Symptoms/General	1.6 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	1.7 units on a scale STANDARD_DEVIATION 0.5 • n=7 Participants	1.7 units on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	1.7 units on a scale STANDARD_DEVIATION 0.6 • n=4 Participants	1.7 units on a scale STANDARD_DEVIATION 0.5 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 14:Genital Symptoms	1.3 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.2 units on a scale STANDARD_DEVIATION 0.9 • n=7 Participants	1.3 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.1 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	1.2 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 15:Hypochondriasis	0.7 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	0.7 units on a scale STANDARD_DEVIATION 0.8 • n=7 Participants	1.0 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants	1.1 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	0.9 units on a scale STANDARD_DEVIATION 0.9 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 16:Loss of Weight	0.3 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	0.2 units on a scale STANDARD_DEVIATION 0.5 • n=7 Participants	0.3 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	0.4 units on a scale STANDARD_DEVIATION 0.7 • n=4 Participants	0.3 units on a scale STANDARD_DEVIATION 0.6 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 17:Insight	0.2 units on a scale STANDARD_DEVIATION 0.4 • n=5 Participants	0.2 units on a scale STANDARD_DEVIATION 0.4 • n=7 Participants	0.1 units on a scale STANDARD_DEVIATION 0.2 • n=5 Participants	0.0 units on a scale STANDARD_DEVIATION 0.2 • n=4 Participants	0.1 units on a scale STANDARD_DEVIATION 0.4 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 18A:Diurnal Variation	0.8 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	0.9 units on a scale STANDARD_DEVIATION 0.9 • n=7 Participants	1.0 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants	1.0 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	0.9 units on a scale STANDARD_DEVIATION 0.9 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 1:Depressed Mood	3.0 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	2.9 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 0.5 • n=4 Participants	2.9 units on a scale STANDARD_DEVIATION 0.6 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 20:Paranoid Symptoms	0.2 units on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	0.2 units on a scale STANDARD_DEVIATION 0.5 • n=7 Participants	0.2 units on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	0.2 units on a scale STANDARD_DEVIATION 0.4 • n=4 Participants	0.2 units on a scale STANDARD_DEVIATION 0.5 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 22B:Helplessness	1.4 units on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	1.5 units on a scale STANDARD_DEVIATION 1.0 • n=7 Participants	1.5 units on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	1.7 units on a scale STANDARD_DEVIATION 1.0 • n=4 Participants	1.5 units on a scale STANDARD_DEVIATION 1.0 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 23B:Hopelessness	1.3 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.3 units on a scale STANDARD_DEVIATION 0.9 • n=7 Participants	1.3 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.3 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	1.3 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 24B:Worthlessness	1.5 units on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	1.5 units on a scale STANDARD_DEVIATION 1.0 • n=7 Participants	1.6 units on a scale STANDARD_DEVIATION 1.1 • n=5 Participants	1.6 units on a scale STANDARD_DEVIATION 1.1 • n=4 Participants	1.5 units on a scale STANDARD_DEVIATION 1.0 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 2:Feelings of Guilt	1.8 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	2.0 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	1.8 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	1.7 units on a scale STANDARD_DEVIATION 0.8 • n=4 Participants	1.8 units on a scale STANDARD_DEVIATION 0.7 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 3:Suicide	0.6 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	0.7 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	0.6 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	0.6 units on a scale STANDARD_DEVIATION 0.8 • n=4 Participants	0.6 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 4:Insomnia Early	1.5 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.4 units on a scale STANDARD_DEVIATION 0.8 • n=7 Participants	1.4 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.4 units on a scale STANDARD_DEVIATION 0.8 • n=4 Participants	1.4 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 5:Insomnia Middle	1.5 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	1.5 units on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	1.4 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.5 units on a scale STANDARD_DEVIATION 0.7 • n=4 Participants	1.5 units on a scale STANDARD_DEVIATION 0.7 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 6:Insomnia Late	1.2 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.3 units on a scale STANDARD_DEVIATION 0.8 • n=7 Participants	1.1 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.1 units on a scale STANDARD_DEVIATION 0.8 • n=4 Participants	1.2 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 7:Work and Activities	2.9 units on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	2.8 units on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	2.8 units on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	2.8 units on a scale STANDARD_DEVIATION 0.5 • n=4 Participants	2.8 units on a scale STANDARD_DEVIATION 0.5 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 8:Retardation	1.1 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	1.0 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	1.1 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.1 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	1.1 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) - Item 9:Agitation	0.9 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants	0.9 units on a scale STANDARD_DEVIATION 0.8 • n=7 Participants	0.9 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants	1.0 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	0.9 units on a scale STANDARD_DEVIATION 0.9 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) Anxiety/Somatization Subscale Score	6.8 units on a scale STANDARD_DEVIATION 2.1 • n=5 Participants	6.9 units on a scale STANDARD_DEVIATION 1.9 • n=7 Participants	7.1 units on a scale STANDARD_DEVIATION 2.3 • n=5 Participants	7.3 units on a scale STANDARD_DEVIATION 2.4 • n=4 Participants	7.0 units on a scale STANDARD_DEVIATION 2.2 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) Bech Subscale Score	12.6 units on a scale STANDARD_DEVIATION 2.0 • n=5 Participants	12.5 units on a scale STANDARD_DEVIATION 1.7 • n=7 Participants	12.4 units on a scale STANDARD_DEVIATION 1.9 • n=5 Participants	12.3 units on a scale STANDARD_DEVIATION 2.2 • n=4 Participants	12.5 units on a scale STANDARD_DEVIATION 2.0 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) Maier Subscale Score	11.8 units on a scale STANDARD_DEVIATION 2.2 • n=5 Participants	11.7 units on a scale STANDARD_DEVIATION 1.9 • n=7 Participants	11.6 units on a scale STANDARD_DEVIATION 2.2 • n=5 Participants	11.6 units on a scale STANDARD_DEVIATION 2.4 • n=4 Participants	11.7 units on a scale STANDARD_DEVIATION 2.2 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) Retardation Subscale Score	8.2 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants	8.0 units on a scale STANDARD_DEVIATION 1.6 • n=7 Participants	8.0 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants	7.9 units on a scale STANDARD_DEVIATION 1.6 • n=4 Participants	8.1 units on a scale STANDARD_DEVIATION 1.6 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) Sleep Subscale Score	4.2 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants	4.3 units on a scale STANDARD_DEVIATION 1.5 • n=7 Participants	3.9 units on a scale STANDARD_DEVIATION 1.7 • n=5 Participants	4.0 units on a scale STANDARD_DEVIATION 1.5 • n=4 Participants	4.1 units on a scale STANDARD_DEVIATION 1.6 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale (HAMD-24) Total Score	28.6 units on a scale STANDARD_DEVIATION 6.0 • n=5 Participants	28.6 units on a scale STANDARD_DEVIATION 5.5 • n=7 Participants	28.7 units on a scale STANDARD_DEVIATION 6.2 • n=5 Participants	29.0 units on a scale STANDARD_DEVIATION 6.7 • n=4 Participants	28.7 units on a scale STANDARD_DEVIATION 6.1 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale - Item 12:Somatic Symptoms/Gastrointestinal	0.7 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	0.6 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	0.6 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	0.7 units on a scale STANDARD_DEVIATION 0.7 • n=4 Participants	0.7 units on a scale STANDARD_DEVIATION 0.7 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale - Item 18B:Diurnal Variation-Severity	0.8 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	0.9 units on a scale STANDARD_DEVIATION 0.9 • n=7 Participants	0.9 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	1.0 units on a scale STANDARD_DEVIATION 0.9 • n=4 Participants	0.9 units on a scale STANDARD_DEVIATION 0.8 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale - Item 19: Depersonalization and Derealization	0.2 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	0.3 units on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	0.2 units on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	0.2 units on a scale STANDARD_DEVIATION 0.5 • n=4 Participants	0.2 units on a scale STANDARD_DEVIATION 0.6 • n=21 Participants
Evaluation - 24-Item Hamilton Depression Rating Scale - Item 21:Obsessional and Compulsive Symptoms	0.1 units on a scale STANDARD_DEVIATION 0.4 • n=5 Participants	0.1 units on a scale STANDARD_DEVIATION 0.4 • n=7 Participants	0.1 units on a scale STANDARD_DEVIATION 0.4 • n=5 Participants	0.1 units on a scale STANDARD_DEVIATION 0.4 • n=4 Participants	0.1 units on a scale STANDARD_DEVIATION 0.4 • n=21 Participants
Evaluation - Clinical Global Impressions of Severity Scale (CGI-S) Score	4.6 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	4.5 units on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	4.7 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	4.7 units on a scale STANDARD_DEVIATION 0.7 • n=4 Participants	4.6 units on a scale STANDARD_DEVIATION 0.7 • n=21 Participants
Evaluation - Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire	28.4 units on a scale STANDARD_DEVIATION 6.0 • n=5 Participants	26.8 units on a scale STANDARD_DEVIATION 6.1 • n=7 Participants	28.6 units on a scale STANDARD_DEVIATION 6.1 • n=5 Participants	28.6 units on a scale STANDARD_DEVIATION 5.4 • n=4 Participants	28.2 units on a scale STANDARD_DEVIATION 6.0 • n=21 Participants
Evaluation - Pain Numerical Rating Scale (NRS) Score Item 1	4.3 units on a scale STANDARD_DEVIATION 2.8 • n=5 Participants	4.1 units on a scale STANDARD_DEVIATION 2.7 • n=7 Participants	4.5 units on a scale STANDARD_DEVIATION 3.1 • n=5 Participants	4.5 units on a scale STANDARD_DEVIATION 2.8 • n=4 Participants	4.4 units on a scale STANDARD_DEVIATION 2.9 • n=21 Participants
Evaluation - Pain Numerical Rating Scale (NRS) Score Item 7	4.7 units on a scale STANDARD_DEVIATION 3.0 • n=5 Participants	4.5 units on a scale STANDARD_DEVIATION 3.1 • n=7 Participants	4.7 units on a scale STANDARD_DEVIATION 3.2 • n=5 Participants	4.9 units on a scale STANDARD_DEVIATION 3.2 • n=4 Participants	4.7 units on a scale STANDARD_DEVIATION 3.1 • n=21 Participants
Evaluation - Sheehan Disability Scale (SDS) Item 1	5.5 units on a scale STANDARD_DEVIATION 2.8 • n=5 Participants	5.4 units on a scale STANDARD_DEVIATION 2.7 • n=7 Participants	5.6 units on a scale STANDARD_DEVIATION 2.7 • n=5 Participants	5.3 units on a scale STANDARD_DEVIATION 2.8 • n=4 Participants	5.5 units on a scale STANDARD_DEVIATION 2.7 • n=21 Participants
Evaluation - Sheehan Disability Scale (SDS) Item 2	6.6 units on a scale STANDARD_DEVIATION 2.4 • n=5 Participants	6.2 units on a scale STANDARD_DEVIATION 2.8 • n=7 Participants	6.4 units on a scale STANDARD_DEVIATION 2.8 • n=5 Participants	5.9 units on a scale STANDARD_DEVIATION 2.5 • n=4 Participants	6.3 units on a scale STANDARD_DEVIATION 2.6 • n=21 Participants
Evaluation - Sheehan Disability Scale (SDS) Item 3	6.5 units on a scale STANDARD_DEVIATION 2.5 • n=5 Participants	6.0 units on a scale STANDARD_DEVIATION 2.6 • n=7 Participants	6.2 units on a scale STANDARD_DEVIATION 2.6 • n=5 Participants	6.0 units on a scale STANDARD_DEVIATION 2.5 • n=4 Participants	6.2 units on a scale STANDARD_DEVIATION 2.6 • n=21 Participants
Evaluation - Sheehan Disability Scale (SDS) Total Score	19.0 units on a scale STANDARD_DEVIATION 6.5 • n=5 Participants	17.8 units on a scale STANDARD_DEVIATION 7.3 • n=7 Participants	18.4 units on a scale STANDARD_DEVIATION 7.1 • n=5 Participants	17.5 units on a scale STANDARD_DEVIATION 7.0 • n=4 Participants	18.3 units on a scale STANDARD_DEVIATION 6.9 • n=21 Participants
Evaluation - Social Adaptation Self-Evaluation Scale (SASS) Total	27.2 units on a scale STANDARD_DEVIATION 7.3 • n=5 Participants	29.1 units on a scale STANDARD_DEVIATION 8.4 • n=7 Participants	27.6 units on a scale STANDARD_DEVIATION 8.2 • n=5 Participants	29.3 units on a scale STANDARD_DEVIATION 8.2 • n=4 Participants	28.0 units on a scale STANDARD_DEVIATION 8.0 • n=21 Participants
History - Age at First Episode	30.0 years STANDARD_DEVIATION 13.2 • n=5 Participants	31.2 years STANDARD_DEVIATION 13.7 • n=7 Participants	30.7 years STANDARD_DEVIATION 13.6 • n=5 Participants	30.0 years STANDARD_DEVIATION 12.6 • n=4 Participants	30.4 years STANDARD_DEVIATION 13.3 • n=21 Participants
History - How Long was Last Major Depressive Disorder (MDD) Episode	4.7 weeks STANDARD_DEVIATION 6.3 • n=5 Participants	5.0 weeks STANDARD_DEVIATION 7.4 • n=7 Participants	5.2 weeks STANDARD_DEVIATION 6.9 • n=5 Participants	6.5 weeks STANDARD_DEVIATION 14.5 • n=4 Participants	5.2 weeks STANDARD_DEVIATION 8.6 • n=21 Participants
History - Interval Between Start of Current and Remission of Last MDD Episode	13.2 weeks STANDARD_DEVIATION 20.1 • n=5 Participants	12.5 weeks STANDARD_DEVIATION 24.3 • n=7 Participants	13.1 weeks STANDARD_DEVIATION 22.1 • n=5 Participants	13.1 weeks STANDARD_DEVIATION 22.2 • n=4 Participants	13.0 weeks STANDARD_DEVIATION 21.8 • n=21 Participants
History - Number of Previous Episodes	4.0 number of previous episodes STANDARD_DEVIATION 4.8 • n=5 Participants	3.8 number of previous episodes STANDARD_DEVIATION 4.3 • n=7 Participants	4.9 number of previous episodes STANDARD_DEVIATION 5.4 • n=5 Participants	5.2 number of previous episodes STANDARD_DEVIATION 5.4 • n=4 Participants	4.5 number of previous episodes STANDARD_DEVIATION 5.1 • n=21 Participants
History - Time Since First Episode Date	12.3 years STANDARD_DEVIATION 11.6 • n=5 Participants	12.5 years STANDARD_DEVIATION 11.6 • n=7 Participants	14.0 years STANDARD_DEVIATION 11.5 • n=5 Participants	14.0 years STANDARD_DEVIATION 12.0 • n=4 Participants	13.2 years STANDARD_DEVIATION 11.7 • n=21 Participants
History - Time Since Most Recent Episode	44.0 weeks STANDARD_DEVIATION 60.2 • n=5 Participants	48.8 weeks STANDARD_DEVIATION 69.5 • n=7 Participants	51.4 weeks STANDARD_DEVIATION 103.3 • n=5 Participants	59.2 weeks STANDARD_DEVIATION 111.2 • n=4 Participants	49.8 weeks STANDARD_DEVIATION 87.3 • n=21 Participants

PRIMARY outcome

Timeframe: baseline, 8 weeks

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Item 7 of the HAMD-24 assesses loss of interest or pleasure in work and activities and is an essential symptom in MDD. Scores range from 0 (no difficulty/no loss) to 4 (difficulty/loss).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=214 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=102 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=220 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=110 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 8 Weeks in 24-Item Hamilton Depression Rating Scale (HAMD-24) Item 7 (Work and Activities)	-1.32 units on a scale Standard Error 0.07	-1.07 units on a scale Standard Error 0.11	-1.37 units on a scale Standard Error 0.07	-0.93 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 8 weeks, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). Please see baseline demographics for subscale total scores.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=214 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=102 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=220 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=110 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Total Score 12 Week Change (n=194,n=59,n=195,n=64)	-12.64 units on a scale Standard Error 0.50	-10.33 units on a scale Standard Error 0.79	-12.11 units on a scale Standard Error 0.47	-8.48 units on a scale Standard Error 0.75
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Maier 8 Week Change (n=214,n=102,n=220,n=110)	-6.11 units on a scale Standard Error 0.27	-4.69 units on a scale Standard Error 0.38	-6.13 units on a scale Standard Error 0.24	-4.45 units on a scale Standard Error 0.33
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Anxiety 12 Week Change (n=194,n=59,n=195,n=64)	-3.52 units on a scale Standard Error 0.16	-3.12 units on a scale Standard Error 0.27	-3.52 units on a scale Standard Error 0.17	-2.44 units on a scale Standard Error 0.27
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Bech 12 Week Change (n=194,n=59,n=195,n=64)	-7.38 units on a scale Standard Error 0.29	-6.17 units on a scale Standard Error 0.47	-6.98 units on a scale Standard Error 0.27	-4.70 units on a scale Standard Error 0.43
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Retardation 12 Week Change (n=194,n=59,n=195,n=64)	-4.72 units on a scale Standard Error 0.19	-4.06 units on a scale Standard Error 0.32	-4.49 units on a scale Standard Error 0.19	-3.05 units on a scale Standard Error 0.31
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Sleep 12 Week Change (n=194,n=59,n=195,n=64)	-2.08 units on a scale Standard Error 0.13	-1.72 units on a scale Standard Error 0.22	-1.91 units on a scale Standard Error 0.12	-1.48 units on a scale Standard Error 0.20
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Total Score 9 Month Change (n=29,n=9,n=33,n=10)	-14.38 units on a scale Standard Error 1.02	-13.38 units on a scale Standard Error 1.86	-9.56 units on a scale Standard Error 1.26	-5.92 units on a scale Standard Error 2.32
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Anxiety 9 Month Change (n=29,n=9,n=33,n=10)	-4.09 units on a scale Standard Error 0.30	-3.88 units on a scale Standard Error 0.56	-3.44 units on a scale Standard Error 0.35	-2.77 units on a scale Standard Error 0.65
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Bech 9 Month Change (n=29,n=9,n=33,n=10)	-8.56 units on a scale Standard Error 0.58	-8.02 units on a scale Standard Error 1.04	-5.80 units on a scale Standard Error 0.70	-4.35 units on a scale Standard Error 1.30
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Retardation 9 Month Change (n=29,n=9,n=33,n=10)	-5.35 units on a scale Standard Error 0.40	-5.83 units on a scale Standard Error 0.72	-3.68 units on a scale Standard Error 0.44	-2.52 units on a scale Standard Error 0.81
Change From Baseline to 12 Week and 9 Month Endpoints in the 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score and HAMD-24 Subscales (8 Week Endpoint for Maier Subscale) Sleep 9 Month Change (n=29,n=9,n=33,n=10)	-2.77 units on a scale Standard Error 0.23	-2.56 units on a scale Standard Error 0.40	-2.55 units on a scale Standard Error 0.26	-1.95 units on a scale Standard Error 0.48

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=193 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=57 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in the HAMD-24 Total Score 12 Week Change	-16.24 units on a scale Standard Error 0.62	-13.24 units on a scale Standard Error 1.01	-15.60 units on a scale Standard Error 0.61	-10.94 units on a scale Standard Error 0.96
Change From Baseline to 12 Week and 9 Month Endpoints in the HAMD-24 Total Score 9 Month Change (n=29, n=8, n=32, n=10)	-17.05 units on a scale Standard Error 1.15	-15.22 units on a scale Standard Error 2.14	-13.49 units on a scale Standard Error 1.45	-9.12 units on a scale Standard Error 2.64

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures depressed mood on a scale of 0 (absent) to 4 (very depressed).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in the HAMD-24 Item 1:Depressed Mood 12 Week Change	-1.86 units on a scale Standard Error 0.07	-1.52 units on a scale Standard Error 0.12	-1.78 units on a scale Standard Error 0.07	-1.15 units on a scale Standard Error 0.12
Change From Baseline to 12 Week and 9 Month Endpoints in the HAMD-24 Item 1:Depressed Mood 9 Month Change (n=29, n=9, n=33, n=10)	-1.44 units on a scale Standard Error 0.20	-1.26 units on a scale Standard Error 0.34	-1.98 units on a scale Standard Error 0.19	-1.65 units on a scale Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures feelings of guilt on a scale of 0 (absent) to 4 (very guilty).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 2:Feelings of Guilt 12 Week Change	-1.19 units on a scale Standard Error 0.06	-1.06 units on a scale Standard Error 0.09	-1.15 units on a scale Standard Error 0.05	-0.89 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 2:Feelings of Guilt 9 Month Change (n=29, n=9, n=33, n=10)	-1.32 units on a scale Standard Error 0.10	-1.21 units on a scale Standard Error 0.17	-1.37 units on a scale Standard Error 0.06	-1.16 units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 Months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures thoughts of suicide on a scale of 0 (absent) to 4 (attempts suicide).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 3:Suicide 12 Week Change	-0.46 units on a scale Standard Error 0.04	-0.30 units on a scale Standard Error 0.06	-0.40 units on a scale Standard Error 0.04	-0.29 units on a scale Standard Error 0.06
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 3:Suicide 9 Month Change (n=29, n= 9, n=33, n=10)	-1.32 units on a scale Standard Error 0.10	-1.21 units on a scale Standard Error 0.17	-1.37 units on a scale Standard Error 0.06	-1.16 units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures early insomnia on a scale of 0 (no difficulty falling asleep) to 2 (complains of nightly difficulty falling asleep).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 4:Insomnia Early 12 Week Change	-0.72 units on a scale Standard Error 0.06	-0.61 units on a scale Standard Error 0.10	-0.68 units on a scale Standard Error 0.06	-0.46 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 4:Insomnia Early 9 Month Change (n=29, n=9, n=33, n=10)	-0.85 units on a scale Standard Error 0.13	-0.77 units on a scale Standard Error 0.23	-0.71 units on a scale Standard Error 0.13	-0.86 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures middle insomnia on a scale of 0 (no difficulty) to 2 (waking during the night).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 5:Insomnia Middle 12 Week Change	-0.69 units on a scale Standard Error 0.05	-0.74 units on a scale Standard Error 0.09	-0.66 units on a scale Standard Error 0.06	-0.59 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 5:Insomnia Middle 9 Month Change (n=29, n=9, n=33, n=10)	-0.99 units on a scale Standard Error 0.11	-0.92 units on a scale Standard Error 0.19	-0.99 units on a scale Standard Error 0.09	-0.67 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures late insomnia on a scale of 0 (no difficulty) to 2 (unable to fall asleep again if gets out of bed).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 6:Insomnia Late 12 Week Change	-0.66 units on a scale Standard Error 0.05	-0.49 units on a scale Standard Error 0.09	-0.57 units on a scale Standard Error 0.05	-0.45 units on a scale Standard Error 0.08
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 6:Insomnia Late 9 Month Change (n=29, n=9, n=33, n=10)	-0.94 units on a scale Standard Error 0.05	-0.87 units on a scale Standard Error 0.08	-0.78 units on a scale Standard Error 0.10	-0.52 units on a scale Standard Error 0.19

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Item 7 of the HAMD-24 assesses loss of interest or pleasure in work and activities and is an essential symptom in MDD. Scores range from 0 (no difficulty/no loss) to 4 (difficulty/loss).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=29 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=9 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=33 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=10 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 9 Month Endpoint in HAMD-24 - Item 7:Work and Activities	-2.43 units on a scale Standard Error 0.10	-2.55 units on a scale Standard Error 0.19	-1.66 units on a scale Standard Error 0.13	-1.50 units on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures slowness of thought and speech; impaired ability to concentrate; decreased motor activity on a scale of 0 (normal speech and thought) to 4 (complete stupor).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 8:Retardation 12 Week Change	-0.72 units on a scale Standard Error 0.04	-0.69 units on a scale Standard Error 0.07	-0.66 units on a scale Standard Error 0.04	-0.51 units on a scale Standard Error 0.07
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 8:Retardation 9 Month Change (n=29, n=9, n=33, n=10)	-0.89 units on a scale Standard Error 0.05	-0.90 units on a scale Standard Error 0.09	-1.66 units on a scale Standard Error 0.13	-1.50 units on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures agitation on a scale of 0 (none) to 4 (hand-wringing, nail-biting)

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 9:Agitation 12 Week Change	-0.47 units on a scale Standard Error 0.04	-0.48 units on a scale Standard Error 0.07	-0.44 units on a scale Standard Error 0.05	-0.41 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 9:Agitation 9 Month Change (n=29, n=9, n=33, n=10)	-0.53 units on a scale Standard Error 0.07	-0.61 units on a scale Standard Error 0.12	-0.57 units on a scale Standard Error 0.11	-0.78 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures anxiety on a scale of 0 (no difficulty) to 4 (fears expressed)

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 10:Anxiety (Psychic) 12 Week Change	-1.15 units on a scale Standard Error 0.06	-0.90 units on a scale Standard Error 0.10	-1.15 units on a scale Standard Error 0.06	-0.81 units on a scale Standard Error 0.10
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 10:Anxiety (Psychic) 9 Month Change (n=29, n=9, n=33, n=10)	-1.23 units on a scale Standard Error 0.12	-1.13 units on a scale Standard Error 0.20	-1.41 units on a scale Standard Error 0.12	-1.70 units on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures physiological concomitants of anxiety on a scale of 0 (absent) to 4 (incapacitating).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 11:Anxiety (Somatic) 12 Week Change	-0.61 units on a scale Standard Error 0.05	-0.65 units on a scale Standard Error 0.09	-0.68 units on a scale Standard Error 0.06	-0.57 units on a scale Standard Error 0.10
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 11:Anxiety (Somatic) 9 Month Change (n=29, n=9, n=33, n=10)	-0.98 units on a scale Standard Error 0.11	-0.94 units on a scale Standard Error 0.19	-1.20 units on a scale Standard Error 0.08	-1.18 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures gastrointestical somatic symptoms on a scale of 0 (none) to 2 (difficulty eating, requires medication for symptoms).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 12:Somatic Symptoms/Gastrointestinal 12 Week Change	-0.44 units on a scale Standard Error 0.03	-0.52 units on a scale Standard Error 0.06	-0.40 units on a scale Standard Error 0.03	-0.32 units on a scale Standard Error 0.05
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 12:Somatic Symptoms/Gastrointestinal 9 Month Change (n=29, n=9, n=33, n=10)	-0.98 units on a scale Standard Error 0.11	-0.94 units on a scale Standard Error 0.19	-0.46 units on a scale Standard Error 0.05	-0.47 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures general somatic symptoms on a scale of 0 (none) to 2 (any clear-cut symptoms).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 13:Somatic Symptoms/General 12 Week Change	-0.91 units on a scale Standard Error 0.05	-0.88 units on a scale Standard Error 0.09	-0.75 units on a scale Standard Error 0.05	-0.49 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 13:Somatic Symptoms/General 9 Month Change (n=29, n=9, n=33, n=10)	-1.36 units on a scale Standard Error 0.11	-1.18 units on a scale Standard Error 0.20	-0.94 units on a scale Standard Error 0.13	-0.83 units on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures genital symptoms (loss of libido, menstrual disturbances) on a scale of 0 (absent) to 2 (severe).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 14:Genital Symptoms 12 Week Change	-0.57 units on a scale Standard Error 0.05	-0.54 units on a scale Standard Error 0.09	-0.55 units on a scale Standard Error 0.06	-0.40 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 14:Genital Symptoms 9 Month Change (n=29, n=9, n=33, n=10)	-0.89 units on a scale Standard Error 0.13	-0.77 units on a scale Standard Error 0.22	-0.68 units on a scale Standard Error 0.08	-0.30 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures hypochondriasis on a scale of 0 (not present) to 4 (hypochondriacal delusions).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 15:Hypochondriasis 12 Week Change	-0.36 units on a scale Standard Error 0.04	-0.41 units on a scale Standard Error 0.06	-0.52 units on a scale Standard Error 0.05	-0.41 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 15:Hypochondriasis 9 Month Change (n=29, n=9, n=33, n=10)	-0.44 units on a scale Standard Error 82.99	-0.53 units on a scale Standard Error 144.40	-0.61 units on a scale Standard Error 0.09	-0.41 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures weight loss since last visit on a scale of 0 (no weight loss) to 2 (definite weight loss caused by present illness).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 16:Loss of Weight 12 Week Change	-0.21 units on a scale Standard Error 0.02	-0.20 units on a scale Standard Error 0.04	-0.25 units on a scale Standard Error 0.02	-0.24 units on a scale Standard Error 0.04
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 16:Loss of Weight 9 Month Change (n=29, n=9, n=33, n=10)	-0.44 units on a scale Standard Error 82.99	-0.53 units on a scale Standard Error 144.40	-0.61 units on a scale Standard Error 0.09	-0.41 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures insight on a scale of 0 (acknowledges being depressed and ill) to 2 (denies being ill at all).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 17:Insight 12 Week Change	-0.08 units on a scale Standard Error 0.01	-0.07 units on a scale Standard Error 0.02	-0.01 units on a scale Standard Error 0.01	-0.01 units on a scale Standard Error 0.02
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 17:Insight 9 Month Change (n=29, n=9, n=33, n=10)	-0.44 units on a scale Standard Error 82.99	-0.53 units on a scale Standard Error 144.40	-0.61 units on a scale Standard Error 0.09	-0.41 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures whether symptoms are worse in morning or evening on a scale of 0 (no variation), 1 (worse in morning), or 2 (worse in evening).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 18A:Diurnal Variation 12 Week Change	-0.32 units on a scale Standard Error 0.05	-0.36 units on a scale Standard Error 0.09	-0.45 units on a scale Standard Error 0.05	-0.13 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 18A:Diurnal Variation 9 Month Change (n=29, n=9, n=33, n=10)	-0.56 units on a scale Standard Error 0.12	-0.26 units on a scale Standard Error 0.20	-0.77 units on a scale Standard Error 0.13	-0.70 units on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures the severity of the diurnal variation on a scale of 0 (none) to 2 (severe).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 18B:Diurnal Variation-Severity 12 Week Change	-0.43 units on a scale Standard Error 0.04	-0.49 units on a scale Standard Error 0.07	-0.42 units on a scale Standard Error 0.05	-0.21 units on a scale Standard Error 0.08
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 18B:Diurnal Variation-Severity 9 Month Change (n=29, n=8, n=32, n=10)	-0.60 units on a scale Standard Error 0.07	-0.54 units on a scale Standard Error 0.12	-0.63 units on a scale Standard Error 0.08	-0.56 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures feelings of unreality on a scale of 0 (absent) to 4 (incapacitating).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 19: Depersonalization and Derealization 12 Week Change	-0.19 units on a scale Standard Error 0.02	-0.21 units on a scale Standard Error 0.03	-0.15 units on a scale Standard Error 0.02	-0.14 units on a scale Standard Error 0.03
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 19: Depersonalization and Derealization 9 Month Change (n=29, n=9, n=33, n=10)	-0.60 units on a scale Standard Error 0.07	-0.54 units on a scale Standard Error 0.12	-0.63 units on a scale Standard Error 0.08	-0.56 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures paranoid symptoms on a scale of 0 (none) to 2 (severe).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 20:Paranoid Symptoms 12 Week Change	-0.15 units on a scale Standard Error 0.02	-0.12 units on a scale Standard Error 0.04	-0.13 units on a scale Standard Error 0.02	-0.11 units on a scale Standard Error 0.03
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 20:Paranoid Symptoms 9 Month Change (n=29, n=9, n=33, n=10)	-0.60 units on a scale Standard Error 0.07	-0.54 units on a scale Standard Error 0.12	-0.63 units on a scale Standard Error 0.08	-0.56 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures obsessional and compulsive symptoms on a scale of 0 (absent) to 2 (severe).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 21:Obsessional and Compulsive Symptoms 12 Week Change	-0.08 units on a scale Standard Error 0.02	-0.06 units on a scale Standard Error 0.03	-0.04 units on a scale Standard Error 0.02	-0.06 units on a scale Standard Error 0.03
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 21:Obsessional and Compulsive Symptoms 9 Month Change (n=29, n=9, n=33, n=10)	-0.60 units on a scale Standard Error 0.07	-0.54 units on a scale Standard Error 0.12	-0.63 units on a scale Standard Error 0.08	-0.56 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures feelings of helplessness on a scale of 0 (absent) to 4 (severe).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 22B:Helplessness 12 Week Change	-0.95 units on a scale Standard Error 0.05	-0.88 units on a scale Standard Error 0.09	-0.98 units on a scale Standard Error 0.06	-0.81 units on a scale Standard Error 0.10
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 22B:Helplessness 9 Month Change (n=29, n=9, n=33, n=10)	-1.16 units on a scale Standard Error 0.09	-0.90 units on a scale Standard Error 0.16	-1.34 units on a scale Standard Error 9.63	-1.24 units on a scale Standard Error 17.77

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures feelings of hopelessness on a scale of 0 (absent) to 4 (expresses feelings of discouragement, despair, and/or pessimism about the future which cannot be dispelled).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 23B:Hopelessness 9 Month Change (n=29, n=9, n=33, n=10)	-1.23 units on a scale Standard Error 0.08	-1.34 units on a scale Standard Error 0.15	-0.92 units on a scale Standard Error 0.07	-0.85 units on a scale Standard Error 0.14
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 23B:Hopelessness 12 Week Change	-0.87 units on a scale Standard Error 0.05	-0.74 units on a scale Standard Error 0.08	-0.80 units on a scale Standard Error 0.05	-0.51 units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures feelings of worthlessness on a scale of 0 (absent) to 4 (severe).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 24B:Worthlessness 12 Week Change	-1.00 units on a scale Standard Error 0.06	-0.95 units on a scale Standard Error 0.09	-0.95 units on a scale Standard Error 0.06	-0.79 units on a scale Standard Error 0.09
Change From Baseline to 12 Week and 9 Month Endpoints in HAMD-24 - Item 24B:Worthlessness 9 Month Change (n=29, n=9, n=33, n=10)	-1.23 units on a scale Standard Error 0.08	-1.34 units on a scale Standard Error 0.15	-0.92 units on a scale Standard Error 0.07	-0.85 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of participants with non-missing data at baseline and post-baseline visit.

The 30-item BPOMS measures mood states and has 6 factors: tension-anxiety, depression-dejection, anxiety-hostility, fatigue, confusion, and vigor. Item scores: 0 (not at all) to 4 (extremely). Each factor scores range from 0 to 20. The Total score is sum of all factor scores minus the factor score for vigor (Total=Ten+Dep+Ang+Fat+Con-Vig).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=193 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=58 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=193 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=63 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment). Total Score (n=192,n=54,n=185,n=61)	-26.41 units on a scale Standard Error 1.44	-18.88 units on a scale Standard Error 2.38	-28.67 units on a scale Standard Error 1.52	-22.67 units on a scale Standard Error 2.37
Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment). Tension-Anxiety (n=193,n=58,n=193,n=62)	-4.37 units on a scale Standard Error 0.26	-3.20 units on a scale Standard Error 0.44	-4.61 units on a scale Standard Error 0.30	-4.05 units on a scale Standard Error 0.49
Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment). Depression-Dejection (n=193,n=58,n=191,n=62)	-6.30 units on a scale Standard Error 0.33	-4.64 units on a scale Standard Error 0.55	-6.78 units on a scale Standard Error 0.34	-5.03 units on a scale Standard Error 0.53
Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment). Anger-Hostility (n=193,n=58,n=192,n=63)	-4.46 units on a scale Standard Error 0.28	-3.09 units on a scale Standard Error 0.46	-4.94 units on a scale Standard Error 0.30	-3.63 units on a scale Standard Error 0.48
Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment). Vigor-Activity (n=192,n=55,192,n=63)	2.55 units on a scale Standard Error 0.29	1.82 units on a scale Standard Error 0.49	2.57 units on a scale Standard Error 0.32	1.48 units on a scale Standard Error 0.51
Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment). Fatigue-Inertia (n=193,n=57,n=190,n=63)	-5.30 units on a scale Standard Error 0.36	-4.68 units on a scale Standard Error 0.59	-6.08 units on a scale Standard Error 0.37	-5.54 units on a scale Standard Error 0.59
Change From Baseline to 12 Week Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment). Confusion-Bewilderment (n=192,n=58,n=189,n=62)	-3.62 units on a scale Standard Error 0.23	-2.86 units on a scale Standard Error 0.39	-3.56 units on a scale Standard Error 0.25	-3.10 units on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=29 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=9 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=33 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=9 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) Anger-Hostility	-4.34 units on a scale Standard Error 0.60	-3.38 units on a scale Standard Error 1.04	-5.98 units on a scale Standard Error 0.40	-4.99 units on a scale Standard Error 0.73
Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) Total Score	-25.67 units on a scale Standard Error 2.83	-22.99 units on a scale Standard Error 4.89	-28.39 units on a scale Standard Error 2.46	-25.51 units on a scale Standard Error 4.68
Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) Tension-Anxiety	-5.36 units on a scale Standard Error 0.51	-4.18 units on a scale Standard Error 0.88	-4.68 units on a scale Standard Error 0.50	-3.50 units on a scale Standard Error 0.94
Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) Depression-Dejection	-7.60 units on a scale Standard Error 0.60	-6.49 units on a scale Standard Error 1.04	-7.18 units on a scale Standard Error 0.63	-5.56 units on a scale Standard Error 1.24
Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) Vigor-Activity	2.63 units on a scale Standard Error 0.78	3.11 units on a scale Standard Error 1.39	2.00 units on a scale Standard Error 0.74	3.04 units on a scale Standard Error 1.42
Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) Fatigue-Inertia	-7.43 units on a scale Standard Error 0.73	-7.40 units on a scale Standard Error 1.26	-6.34 units on a scale Standard Error 0.59	-7.03 units on a scale Standard Error 1.17
Change From Baseline to 9 Month Endpoint in 30-Item Brief Profile of Mood States (BPOMS) Scale and Subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) Confusion-Bewilderment	-3.95 units on a scale Standard Error 0.45	-2.47 units on a scale Standard Error 0.79	-3.54 units on a scale Standard Error 0.35	-3.07 units on a scale Standard Error 0.64

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Number of participants with non-missing data at baseline and post-baseline visit.

The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Individual item scores range from 0 to 10. Total scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Work Life (n=133,n=43,n=140,n=49)	-2.47 units on a scale Standard Error 0.22	-2.12 units on a scale Standard Error 0.34	-1.98 units on a scale Standard Error 0.22	-1.22 units on a scale Standard Error 0.36
Change From Baseline to 12 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Social Life (n=194,n=59,n=195,n=63)	-2.93 units on a scale Standard Error 0.19	-2.50 units on a scale Standard Error 0.31	-2.67 units on a scale Standard Error 0.19	-1.97 units on a scale Standard Error 0.30
Change From Baseline to 12 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Family Life (n=194,n=59,n=195,n=63)	-2.81 units on a scale Standard Error 0.19	-2.19 units on a scale Standard Error 0.32	-2.66 units on a scale Standard Error 0.19	-1.56 units on a scale Standard Error 0.31
Change From Baseline to 12 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Total Score (n=195,n=59,n=195,n=63)	-8.32 units on a scale Standard Error 0.53	-6.84 units on a scale Standard Error 0.87	-7.70 units on a scale Standard Error 0.52	-4.94 units on a scale Standard Error 0.84

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=29 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=9 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=33 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=10 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 9 Month Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Work Life (n=22, n=8, n=22, n=7)	-3.88 units on a scale Standard Error 0.69	-4.01 units on a scale Standard Error 1.10	-2.26 units on a scale Standard Error 0.37	-2.16 units on a scale Standard Error 0.66
Change From Baseline to 9 Month Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Social Life (n=29, n=9, n=33, n=10)	-4.15 units on a scale Standard Error 0.37	-4.35 units on a scale Standard Error 0.65	-3.88 units on a scale Standard Error 0.33	-3.66 units on a scale Standard Error 0.62
Change From Baseline to 9 Month Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Family Life (n=29, n=9, n=33, n=10)	-3.46 units on a scale Standard Error 0.36	-2.99 units on a scale Standard Error 0.64	-3.30 units on a scale Standard Error 0.34	-3.07 units on a scale Standard Error 0.66
Change From Baseline to 9 Month Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores Total Score (n=29, n=9, n=33, n=10)	-11.60 units on a scale Standard Error 1.02	-11.15 units on a scale Standard Error 1.79	-9.42 units on a scale Standard Error 0.97	-8.67 units on a scale Standard Error 1.88

SECONDARY outcome

Timeframe: Over 12 weeks

Relative contribution of improvement on the mood states, defined by BPOMS total score (calculated from subscales) to overall improvement in work and activities, HAMD-24 item 7 using path analysis.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=214 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=102 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=220 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=110 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7 Direct Treatment Effect	-0.032 coefficient	-0.012 coefficient	0.219 coefficient	0.087 coefficient
Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7 Indirect Treatment Effect from BPOMS Total Score	0.376 coefficient	0.145 coefficient	0.209 coefficient	0.083 coefficient
Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7 Total Treatment Effect	0.343 coefficient	0.132 coefficient	0.428 coefficient	0.170 coefficient

SECONDARY outcome

Timeframe: over 12 weeks

For Group A, at least one effect was in the opposite direction, percent of total effect was not calculated.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=214 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7 - Percent of Total Effect Direct Treatment Effect	51.14 percent of total effect	—	—	—
Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7 - Percent of Total Effect Indirect Treatment Effect from BPOMS Total Score	48.86 percent of total effect	—	—	—
Path Analysis of BPOMS Total Score to Overall Improvement in HAMD-24 Item 7 - Percent of Total Effect Total Treatment Effect	100.00 percent of total effect	—	—	—

SECONDARY outcome

Timeframe: over 12 weeks

Relative contribution of improvement on the mood states, defined by BPOMS total score (determined from subscales) to overall improvement in SDS total score using path analysis.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=214 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=102 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=220 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=110 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Path Analysis of BPOMS Total Score to Overall Improvement in Sheehan Disability Scale (SDS) Total Score Direct Treatment Effect	-0.577 coefficient	-0.032 coefficient	0.955 coefficient	0.052 coefficient
Path Analysis of BPOMS Total Score to Overall Improvement in Sheehan Disability Scale (SDS) Total Score Indirect Treatment Effect from BPOMS Total Score	2.754 coefficient	0.151 coefficient	1.761 coefficient	0.095 coefficient
Path Analysis of BPOMS Total Score to Overall Improvement in Sheehan Disability Scale (SDS) Total Score Total Treatment Effect	2.177 coefficient	0.120 coefficient	2.716 coefficient	0.147 coefficient

SECONDARY outcome

Timeframe: Over 12 weeks

For Group A, at least one effect was in the opposite direction, percent of total effect was not calculated.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=214 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Path Analysis of BPOMS Total Score to Overall Improvement in SDS Total Score - Percent of Total Effect Direct Treatment Effect	35.17 percent of total effect	—	—	—
Path Analysis of BPOMS Total Score to Overall Improvement in SDS Total Score - Percent of Total Effect Indirect Treatment Effect from BPOMS Total Score	64.83 percent of total effect	—	—	—
Path Analysis of BPOMS Total Score to Overall Improvement in SDS Total Score - Percent of Total Effect Total Treatment Effect	100.00 percent of total effect	—	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

A 16-item patient-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=58 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=62 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Total Score 12 Week Change	-6.31 units on a scale Standard Deviation 0.34	-5.65 units on a scale Standard Deviation 0.55	-6.54 units on a scale Standard Deviation 0.33	-5.21 units on a scale Standard Deviation 0.52
Change From Baseline to 12 Week and 9 Month Endpoints in 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Total Score 9 Month Change (n=29, n=9, n=33, n=9)	-8.41 units on a scale Standard Deviation 0.77	-6.85 units on a scale Standard Deviation 1.36	-7.17 units on a scale Standard Deviation 0.59	-6.15 units on a scale Standard Deviation 1.11

SECONDARY outcome

Timeframe: 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Probability of remission as measured by the HAMD17 Total Score ≤ 7 and by the QIDS16SR Total Score ≤ 5. The visitwise percentages of patients meeting criteria in the Acute Therapy Phase for remission (visitwise binary outcome, yes/no) will be analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis will include the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Probability of Remission at 12 Week Endpoint and Sustained Remission at 9 Month Endpoint 12 Week HAMD-17 Total (n=194,n=59,n=195,n=64)	0.38 probability of remission Standard Error 0.21	0.35 probability of remission Standard Error 0.31	0.35 probability of remission Standard Error 0.19	0.18 probability of remission Standard Error 0.34
Probability of Remission at 12 Week Endpoint and Sustained Remission at 9 Month Endpoint 12 Week QIDS16 Total Score (n=194,n=58,n=194,n=62)	0.30 probability of remission Standard Error 0.19	0.30 probability of remission Standard Error 0.30	0.33 probability of remission Standard Error 0.17	0.19 probability of remission Standard Error 0.30
Probability of Remission at 12 Week Endpoint and Sustained Remission at 9 Month Endpoint 9 Month HAMD-17 Total Score (n=29,n=9,n=33,n=10)	0.63 probability of remission Standard Error 0.35	0.62 probability of remission Standard Error 0.63	0.70 probability of remission Standard Error 0.36	0.57 probability of remission Standard Error 0.65
Probability of Remission at 12 Week Endpoint and Sustained Remission at 9 Month Endpoint 9 Month QIDS16 Total Score (n=29,n=9,n=33,n=9)	0.71 probability of remission Standard Error 0.31	0.54 probability of remission Standard Error 0.51	0.71 probability of remission Standard Error 0.35	0.64 probability of remission Standard Error 0.66

SECONDARY outcome

Timeframe: 12 weeks

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Probability of response as measured by ≥ 50% Improvement in the HAMD17 Total Score and ≥ 50% Improvement in the QIDS16SR Total Score. The visitwise percentages of patients meeting criteria in the Acute Therapy Phase for response (visitwise binary outcome, yes/no) will be analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis will include the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Probability of Response at 12 Week Endpoint HAMD-17 Total Score (n=194,n=59,n=195,n=64)	0.63 probability of response Standard Error 0.16	0.60 probability of response Standard Error 0.27	0.63 probability of response Standard Error 0.16	0.46 probability of response Standard Error 0.26
Probability of Response at 12 Week Endpoint QIDS16 Total Score (n=194,n=58,n=194,n=62)	0.44 probability of response Standard Error 0.15	0.41 probability of response Standard Error 0.26	0.45 probability of response Standard Error 0.16	0.34 probability of response Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Item 1=Average musculoskeletal pain severity over the last week as measured by an 11-point Likert scale. Scores range from 0 (no pain) to 10 (worst possible pain). Item 7=How much they have been bothered by pain over the last week. Scores range from 0 (not bothered at all)to 10 (extremely bothered).

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=193 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=63 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in Pain Numerical Rating Scale (NRS) Item 1 - 12 Week Change	-1.14 units on a scale Standard Deviation 0.16	-1.35 units on a scale Standard Deviation 0.26	-0.96 units on a scale Standard Deviation 0.18	-1.16 units on a scale Standard Deviation 0.30
Change From Baseline to 12 Week and 9 Month Endpoints in Pain Numerical Rating Scale (NRS) Item 7 - 12 Week Change	-1.33 units on a scale Standard Deviation 0.17	-1.73 units on a scale Standard Deviation 0.27	-1.14 units on a scale Standard Deviation 0.18	-1.36 units on a scale Standard Deviation 0.30
Change From Baseline to 12 Week and 9 Month Endpoints in Pain Numerical Rating Scale (NRS) Item 1 - 9 Month Change (n=29, n=9, n=33, n=10)	-1.30 units on a scale Standard Deviation 0.41	-0.10 units on a scale Standard Deviation 0.73	-2.10 units on a scale Standard Deviation 0.41	-2.36 units on a scale Standard Deviation 0.75
Change From Baseline to 12 Week and 9 Month Endpoints in Pain Numerical Rating Scale (NRS) Item 7 - 9 Month Change (n=29, n=9, n=33, n=10)	-1.56 units on a scale Standard Deviation 0.42	-0.42 units on a scale Standard Deviation 0.74	-2.24 units on a scale Standard Deviation 0.35	-2.11 units on a scale Standard Deviation 0.64

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoint in the Clinical Global Impression-Severity Scale (CGI-S) 12 Week Change	-1.93 units on a scale Standard Error 0.08	-1.58 units on a scale Standard Error 0.14	-1.97 units on a scale Standard Error 0.09	-1.25 units on a scale Standard Error 0.15
Change From Baseline to 12 Week and 9 Month Endpoint in the Clinical Global Impression-Severity Scale (CGI-S) 9 Month Change (n=29, n=9, n=33, n=10)	-2.14 units on a scale Standard Error 0.22	-1.97 units on a scale Standard Error 0.40	-2.61 units on a scale Standard Error 0.21	-2.23 units on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

A 7-item patitent-rated questionnaire pertaining to a patient's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each of the 7 questions is scored on a 6-point scale ranging fom 1 (greater than normal) to 6 (totally absent). Total score ranges from 7 to 42.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=193 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=64 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) 12 Week Change	-7.60 units on a scale Standard Error 0.46	-6.39 units on a scale Standard Error 0.74	-7.96 units on a scale Standard Error 0.47	-6.85 units on a scale Standard Error 0.74
Change From Baseline to 12 Week and 9 Month Endpoints in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) 9 Month Change (n=29, n=9, n=32, n=10)	-7.17 units on a scale Standard Error 0.88	-7.13 units on a scale Standard Error 1.54	-8.19 units on a scale Standard Error 0.84	-6.77 units on a scale Standard Error 1.48

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

A 21-item self-rated scale that evaluates patient social motivation and behavior in depression. Each of the 21 items is scored from 0 (minimal social adjustment) to 3 (maximal social adjustment). Total score ranges from 0 to 60.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=187 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=57 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=185 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=62 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in the Social Adaptation Self-evaluation Scale (SASS) Total Score 12 Week Change	7.18 units on a scale Standard Error 0.62	3.40 units on a scale Standard Error 0.99	7.54 units on a scale Standard Error 0.61	4.52 units on a scale Standard Error 0.92
Change From Baseline to 12 Week and 9 Month Endpoints in the Social Adaptation Self-evaluation Scale (SASS) Total Score 9 Month Change (n=28, n=9, n=30, n=10)	8.00 units on a scale Standard Error 1.14	5.30 units on a scale Standard Error 1.92	13.81 units on a scale Standard Error 1.04	9.28 units on a scale Standard Error 1.92

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Sitting systolic and diastolic blood pressure.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=58 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=196 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=63 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in Blood Pressure Systolic Blood Pressure (SBP) - 12 Week Change	-0.12 mm Hg Standard Error 0.78	0.05 mm Hg Standard Error 1.33	0.73 mm Hg Standard Error 0.76	-2.95 mm Hg Standard Error 1.25
Change From Baseline to 12 Week and 9 Month Endpoints in Blood Pressure Diastolic Blood Pressure (DBP) - 12 Week Change	0.48 mm Hg Standard Error 0.51	-0.58 mm Hg Standard Error 0.88	1.97 mm Hg Standard Error 0.61	-0.50 mm Hg Standard Error 1.00
Change From Baseline to 12 Week and 9 Month Endpoints in Blood Pressure SBP - 9 Month Change (n=28, n=9, n=33, n=10)	-1.18 mm Hg Standard Error 2.31	-0.44 mm Hg Standard Error 4.02	-2.22 mm Hg Standard Error 1.63	-0.54 mm Hg Standard Error 2.91
Change From Baseline to 12 Week and 9 Month Endpoints in Blood Pressure DBP - 9 Month Change (n=28, n=9, n=33, n=10)	-2.25 mm Hg Standard Error 1.25	1.46 mm Hg Standard Error 2.18	-1.52 mm Hg Standard Error 1.47	-1.05 mm Hg Standard Error 2.69

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=58 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=196 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=63 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in Pulse Rate 12 Week Change	1.40 beats per minute Standard Error 0.57	-1.52 beats per minute Standard Error 1.01	0.68 beats per minute Standard Error 0.70	-2.05 beats per minute Standard Error 1.18
Change From Baseline to 12 Week and 9 Month Endpoints in Pulse Rate 9 Month Change (n=28, n=9, n=33, n=10)	1.08 beats per minute Standard Error 1.79	-0.30 beats per minute Standard Error 3.11	1.18 beats per minute Standard Error 1.17	-3.04 beats per minute Standard Error 2.05

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=58 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=195 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=63 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Change From Baseline to 12 Week and 9 Month Endpoints in Weight 12 Week Change	-0.54 kilograms Standard Error 0.20	0.38 kilograms Standard Error 0.31	-0.38 kilograms Standard Error 0.20	-0.23 kilograms Standard Error 0.30
Change From Baseline to 12 Week and 9 Month Endpoints in Weight 9 Month Change (n=28, n=9, n=33, n=10)	-1.18 kilograms Standard Error 2.31	-0.44 kilograms Standard Error 4.02	-0.94 kilograms Standard Error 0.55	0.06 kilograms Standard Error 1.02

SECONDARY outcome

Timeframe: over 12 weeks

Population: Number of participants wtih a normal baseline and at least one post-baseline measurement.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=250 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=120 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=254 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=128 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Abnormal Vital Signs at Anytime Over 12 Weeks Sitting Pulse Rate - High	1 participants	0 participants	1 participants	0 participants
Abnormal Vital Signs at Anytime Over 12 Weeks Weight - Gain	0 participants	0 participants	0 participants	0 participants
Abnormal Vital Signs at Anytime Over 12 Weeks Weight - Loss	0 participants	1 participants	2 participants	0 participants
Abnormal Vital Signs at Anytime Over 12 Weeks Sitting Systolic Blood Pressure - High	3 participants	1 participants	6 participants	0 participants
Abnormal Vital Signs at Anytime Over 12 Weeks Sitting Diastolic Blood Pressure - High	2 participants	0 participants	2 participants	3 participants

SECONDARY outcome

Timeframe: over 9 months

Population: Number of participants with a normal baseline and at least oone post-baseline measurement.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=250 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=120 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=254 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=128 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Abnormal Vital Signs at Anytime Over 9 Months Sitting Pulse - High	1 participants	0 participants	2 participants	0 participants
Abnormal Vital Signs at Anytime Over 9 Months Weight - Gain	2 participants	0 participants	3 participants	0 participants
Abnormal Vital Signs at Anytime Over 9 Months Weight - Loss	5 participants	1 participants	5 participants	0 participants
Abnormal Vital Signs at Anytime Over 9 Months Sitting Systolic Blood Pressure - High	4 participants	2 participants	7 participants	0 participants
Abnormal Vital Signs at Anytime Over 9 Months Sitting Diastolic Blood Pressure - High	2 participants	0 participants	4 participants	3 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Number of participants with a normal baseline and at least one post-baseline measurement.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=250 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=120 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=254 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=128 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Abnormal Vital Signs at 12 Week Endpoint Weight - Loss	0 participants	1 participants	2 participants	0 participants
Abnormal Vital Signs at 12 Week Endpoint Sitting Pulse Rate - High	0 participants	0 participants	1 participants	0 participants
Abnormal Vital Signs at 12 Week Endpoint Weight - Gain	0 participants	0 participants	0 participants	0 participants
Abnormal Vital Signs at 12 Week Endpoint Sitting Systolic Blood Pressure - High	0 participants	0 participants	4 participants	0 participants
Abnormal Vital Signs at 12 Week Endpoint Sitting Diastolic Blood Pressure - High	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: 9 months

Population: Number of participants with a normal baseline and at least one post-baseline measurement.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=250 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=120 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=254 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=128 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Abnormal Vital Signs at 9 Month Endpoint Weight - Loss	5 participants	1 participants	4 participants	0 participants
Abnormal Vital Signs at 9 Month Endpoint Sitting Systolic Blood Pressure - High	1 participants	0 participants	4 participants	0 participants
Abnormal Vital Signs at 9 Month Endpoint Sitting Pulse - High	0 participants	0 participants	1 participants	0 participants
Abnormal Vital Signs at 9 Month Endpoint Weight - Gain	2 participants	0 participants	3 participants	0 participants
Abnormal Vital Signs at 9 Month Endpoint Sitting Diastolic Blood Pressure - High	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and at least one post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=214 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=102 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=220 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=110 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Bilirubin, Creatinine, Uric Acid Bilirubin - 12 Week Change	0.10 micromole per Liter Standard Deviation 4.09	-0.19 micromole per Liter Standard Deviation 3.63	-0.51 micromole per Liter Standard Deviation 3.92	0.13 micromole per Liter Standard Deviation 3.64
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Bilirubin, Creatinine, Uric Acid Creatinine - 12 Week Change	-1.56 micromole per Liter Standard Deviation 9.55	-0.85 micromole per Liter Standard Deviation 8.27	-1.21 micromole per Liter Standard Deviation 8.95	0.82 micromole per Liter Standard Deviation 7.85
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Bilirubin, Creatinine, Uric Acid Uric Acid - 12 Week Change	-2.77 micromole per Liter Standard Deviation 48.20	5.74 micromole per Liter Standard Deviation 41.92	-12.36 micromole per Liter Standard Deviation 46.02	7.05 micromole per Liter Standard Deviation 44.20
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Bilirubin, Creatinine, Uric Acid Bilirubin - 9 Month Change (n=193,n=60,n=202,n=66)	-0.13 micromole per Liter Standard Deviation 4.04	-0.12 micromole per Liter Standard Deviation 2.94	-0.56 micromole per Liter Standard Deviation 3.77	0.25 micromole per Liter Standard Deviation 3.56
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Bilirubin, Creatinine, Uric Acid Uric Acid - 9 Month Change (n=193,n=60,n=202,n=66)	-2.11 micromole per Liter Standard Deviation 48.77	-2.25 micromole per Liter Standard Deviation 42.59	-8.66 micromole per Liter Standard Deviation 47.85	6.50 micromole per Liter Standard Deviation 44.80

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and at least one post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=191 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=57 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=196 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=67 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Hematocrit Hematocrit - 12 Week Change	-0.00 Proportion of 1.0 Standard Deviation 0.03	-0.01 Proportion of 1.0 Standard Deviation 0.03	0.00 Proportion of 1.0 Standard Deviation 0.03	-0.01 Proportion of 1.0 Standard Deviation 0.03
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Hematocrit Hematocrit - 9 Month Change (n=194,n=59,=197,n=67)	-0.00 Proportion of 1.0 Standard Deviation 0.03	-0.00 Proportion of 1.0 Standard Deviation 0.03	0.00 Proportion of 1.0 Standard Deviation 0.03	-0.01 Proportion of 1.0 Standard Deviation 0.03

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and at least one post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=191 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=57 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=196 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=67 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Mean Cell Volume (MCV) MCV - 12 Week Change	0.98 femtoliter Standard Deviation 2.85	1.30 femtoliter Standard Deviation 3.30	0.71 femtoliter Standard Deviation 3.23	-0.47 femtoliter Standard Deviation 3.18
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Mean Cell Volume (MCV) MCV - 9 Month Change (n=194,n=59,n=197,n=67)	1.07 femtoliter Standard Deviation 2.90	1.66 femtoliter Standard Deviation 3.08	0.88 femtoliter Standard Deviation 3.36	-0.31 femtoliter Standard Deviation 3.48

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and at least one post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=192 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=58 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=202 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=66 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Chloride, Urea Nitrogen, Cholesterol, Sodium Chloride - 12 Week Change	-0.80 millimole per Liter Standard Deviation 2.85	0.24 millimole per Liter Standard Deviation 2.62	-0.91 millimole per Liter Standard Deviation 2.75	-0.39 millimole per Liter Standard Deviation 2.51
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Chloride, Urea Nitrogen, Cholesterol, Sodium Urea Nitrogen - 12 Week Change	-0.06 millimole per Liter Standard Deviation 1.29	0.26 millimole per Liter Standard Deviation 1.04	0.01 millimole per Liter Standard Deviation 1.20	0.15 millimole per Liter Standard Deviation 1.38
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Chloride, Urea Nitrogen, Cholesterol, Sodium Chloride - 9 Month Change (n=193,n=60,n=202,n=66)	-0.74 millimole per Liter Standard Deviation 2.92	0.54 millimole per Liter Standard Deviation 2.44	-0.82 millimole per Liter Standard Deviation 2.71	-0.31 millimole per Liter Standard Deviation 2.40
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Chloride, Urea Nitrogen, Cholesterol, Sodium Cholesterol - 9 Month (n=193,n=60,n=202,n=66)	-0.06 millimole per Liter Standard Deviation 0.70	-0.30 millimole per Liter Standard Deviation 0.78	0.04 millimole per Liter Standard Deviation 0.75	-0.08 millimole per Liter Standard Deviation 0.51
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Chloride, Urea Nitrogen, Cholesterol, Sodium Sodium - 9 Month Change (n=193,n=60,n=202,n=66)	-1.67 millimole per Liter Standard Deviation 3.30	-0.73 millimole per Liter Standard Deviation 2.47	-1.86 millimole per Liter Standard Deviation 3.16	-1.73 millimole per Liter Standard Deviation 3.12

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 9 months

Population: Number of participants with non-missing data at baseline and at least post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=187 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=56 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=193 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=67 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Platelet Count 12 Week Change	8.11 Billions per Liter Standard Deviation 37.00	-7.10 Billions per Liter Standard Deviation 38.83	10.55 Billions per Liter Standard Deviation 37.53	12.02 Billions per Liter Standard Deviation 51.41
Statistically Significant Changes in Baseline to 12 Week and 9 Month Endpoints Laboratory Values - Platelet Count 9 Month Change (n=191, n=58, n=194, n=67)	8.06 Billions per Liter Standard Deviation 37.62	-10.17 Billions per Liter Standard Deviation 35.73	5.96 Billions per Liter Standard Deviation 39.44	10.18 Billions per Liter Standard Deviation 51.19

SECONDARY outcome

Timeframe: baseline, 9 months

Population: Number of participants with non-missing data at baseline and at least one post baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=193 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=60 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=202 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=66 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Changes in Baseline to 9 Month Endpoint Laboratory Values - Alkaline Phosphatase	-0.18 Units per Liter Standard Deviation 10.61	-2.30 Units per Liter Standard Deviation 10.20	0.23 Units per Liter Standard Deviation 10.94	-3.75 Units per Liter Standard Deviation 8.19

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Number of participants with non-missing data at baseline and at least one post-baseline visit.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=197 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=67 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Changes in Baseline to 9 Month Endpoint Laboratory Values - Hemoglobin	-0.13 millimoles per Liter (iron) Standard Deviation 0.45	-0.19 millimoles per Liter (iron) Standard Deviation 0.54	-0.01 millimoles per Liter (iron) Standard Deviation 0.47	-0.17 millimoles per Liter (iron) Standard Deviation 0.53

SECONDARY outcome

Timeframe: over 3 months

Population: Number of participants with a normal baseline and at least one post-baseline measurement.

The number of participants with statistically significant abnormal lab values at anytime and at 12 week endpoint were the same.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=191 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=57 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=201 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=66 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Abnormal Laboratory Values at Anytime/12 Week Endpoint Lymphocytes - High (n=186,n=57,n=195,n=66)	1 participants	3 participants	2 participants	1 participants
Statistically Significant Abnormal Laboratory Values at Anytime/12 Week Endpoint Potassium - Low (n=191,n=57,n=201,n=66)	0 participants	0 participants	1 participants	3 participants

SECONDARY outcome

Timeframe: over 9 months

Population: Number of participants with a normal baseline at at least one post-baseline measurement.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=194 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=202 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=67 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Abnormal Laboratory Values at Anytime During 9 Months Lymphocytes - High (n=189,n=59,n=196,n=66)	1 participants	4 participants	2 participants	1 participants
Statistically Significant Abnormal Laboratory Values at Anytime During 9 Months Potassium - Low (n=194,n=59,n=202,n=67)	0 participants	0 participants	1 participants	3 participants

SECONDARY outcome

Timeframe: 9 months

Population: Number of participants with a normal baseline and at least one post-baseline measurement.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=189 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=59 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=196 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=66 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Statistically Significant Abnormal Laboratory Values at 9 Month Endpoint Lymphocytes - High (n=189,n=59,n=196,n=66)	1 participants	4 participants	1 participants	1 participants
Statistically Significant Abnormal Laboratory Values at 9 Month Endpoint Hemoglobin - Low (n=184,n=54,n=184,n=63)	5 participants	2 participants	2 participants	4 participants

SECONDARY outcome

Timeframe: over 9 months

Population: Number of randomized participants in each treatment group.

Outcome measures

Outcome measures
Measure	Group A - Duloxetine n=247 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group A - Placebo n=271 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).	Group B - Duloxetine n=104 Participants duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Group B - Placebo n=154 Participants placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Summary of Adverse Events Leading to Discontinuation Dizziness	2 participants	1 participants	1 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Headache	1 participants	0 participants	2 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Nausea	5 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Rash	2 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Fatigue	2 participants	2 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Insomnia	2 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Suicide attempt	1 participants	1 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Weight increased	0 participants	0 participants	2 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Abdominal pain lower	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Abnormal dreams	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Asthma	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Blood pressure increased	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Chest pain	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Completed suicide	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Constipation	2 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Crying	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Depression	0 participants	1 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Diarrhoea	1 participants	1 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Disturbance in attention	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Dry mouth	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Dysgeusia	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Hepatic function abnormal	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Hernia	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Hyperhidrosis	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Hypertension	1 participants	1 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Influenza	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Irritability	1 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Lower gastrointestinal haemorrhage	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Lower limb fracture	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Mania	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Migraine	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Muscular weakness	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Non-cardiac chest pain	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Paranoia	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Pregnancy	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Restlessness	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Road traffic accident	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Ruptured cerebral aneurysm	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Pneumonia	1 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Tremor	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Urinary hesitation	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Urinary retention	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Wound infection staphylococcal	0 participants	0 participants	1 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Anorgasmia	0 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Astigmatism	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Cardiac failure congestive	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Depressive symptom	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Dyspepsia	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Gamma-glutamyltransferase increased	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Hepatic enzyme increased	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Libido decreased	0 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Night sweats	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Myocardial infarction	0 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Nightmare	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Palpitations	0 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Pruritus	0 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Sexual dysfunction	0 participants	1 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Somnolence	1 participants	0 participants	0 participants	0 participants
Summary of Adverse Events Leading to Discontinuation Sedation	0 participants	0 participants	0 participants	1 participants
Summary of Adverse Events Leading to Discontinuation Vomiting	0 participants	1 participants	0 participants	0 participants

Adverse Events

Duloxetine

Serious events: 18 serious events

Other events: 497 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 237 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Cardiac disorders Cardiac failure congestive	0.19% 1/518 • Number of events 1	0.00% 0/258
Cardiac disorders Myocardial infarction	0.00% 0/518	0.39% 1/258 • Number of events 1
Cardiac disorders Pericardial effusion	0.19% 1/518 • Number of events 1	0.00% 0/258
Cardiac disorders Pericarditis	0.19% 1/518 • Number of events 1	0.00% 0/258
Gastrointestinal disorders Colitis	0.19% 1/518 • Number of events 1	0.00% 0/258
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/518	0.39% 1/258 • Number of events 1
General disorders Fatigue	0.19% 1/518 • Number of events 1	0.00% 0/258
General disorders Non-cardiac chest pain	0.19% 1/518 • Number of events 1	0.00% 0/258
Hepatobiliary disorders Biliary colic	0.00% 0/518	0.39% 1/258 • Number of events 1
Infections and infestations Diverticulitis	0.00% 0/518	0.39% 1/258 • Number of events 1
Infections and infestations Gangrene	0.00% 0/518	0.39% 1/258 • Number of events 1
Infections and infestations Gastroenteritis	0.19% 1/518 • Number of events 1	0.00% 0/258
Infections and infestations Oesophageal candidiasis	0.00% 0/518	0.39% 1/258 • Number of events 1
Infections and infestations Pneumonia	0.19% 1/518 • Number of events 1	0.39% 1/258 • Number of events 1
Infections and infestations Pyelonephritis	0.19% 1/518 • Number of events 1	0.00% 0/258
Infections and infestations Sepsis	0.00% 0/518	0.39% 1/258 • Number of events 1
Infections and infestations Sinusitis	0.19% 1/518 • Number of events 1	0.00% 0/258
Infections and infestations Staphylococcal infection	0.19% 1/518 • Number of events 1	0.39% 1/258 • Number of events 1
Infections and infestations Subcutaneous abscess	0.19% 1/518 • Number of events 1	0.00% 0/258
Infections and infestations Tooth infection	0.19% 1/518 • Number of events 1	0.00% 0/258
Infections and infestations Urinary tract infection	0.00% 0/518	0.39% 1/258 • Number of events 1
Infections and infestations Wound infection staphylococcal	0.00% 0/518	0.39% 1/258 • Number of events 1
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/518	0.39% 1/258 • Number of events 1
Injury, poisoning and procedural complications Road traffic accident	0.19% 1/518 • Number of events 1	0.00% 0/258
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/518	0.39% 1/258 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer metastatic	0.19% 1/518 • Number of events 1	0.00% 0/258
Nervous system disorders Ruptured cerebral aneurysm	0.19% 1/518 • Number of events 1	0.00% 0/258
Nervous system disorders Status migrainosus	0.19% 1/518 • Number of events 1	0.00% 0/258
Pregnancy, puerperium and perinatal conditions Ruptured ectopic pregnancy	0.19% 1/518 • Number of events 1	0.00% 0/258
Psychiatric disorders Completed suicide	0.00% 0/518	0.39% 1/258 • Number of events 1
Psychiatric disorders Depression	0.19% 1/518 • Number of events 1	0.39% 1/258 • Number of events 1
Psychiatric disorders Homicidal ideation	0.19% 1/518 • Number of events 1	0.00% 0/258
Psychiatric disorders Suicide attempt	0.39% 2/518 • Number of events 2	0.39% 1/258 • Number of events 1
Reproductive system and breast disorders Ovarian cyst	0.19% 1/518 • Number of events 1	0.00% 0/258
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/518	0.39% 1/258 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.19% 1/518 • Number of events 1	0.00% 0/258
Vascular disorders Deep vein thrombosis	0.19% 1/518 • Number of events 1	0.00% 0/258

Other adverse events

Other adverse events
Measure	Duloxetine duloxetine 60 mg every day (QD), by mouth (PO) for 3 months, after which may be increased to duloxetine 120 mg QD, PO for 6 months	Placebo placebo every day (QD), by mouth (PO) for up to 9 months, may be increased to duloxetine 60 mg QD, PO during the first 3 months as part of a rescue plan with pre-defined criteria (Patients meeting criteria will automatically be assigned to duloxetine 60 mg QD).
Endocrine disorders Hypothyroidism	3.7% 19/518 • Number of events 19	5.8% 15/258 • Number of events 15
Gastrointestinal disorders Constipation	12.2% 63/518 • Number of events 71	11.6% 30/258 • Number of events 32
Gastrointestinal disorders Diarrhoea	12.0% 62/518 • Number of events 69	11.6% 30/258 • Number of events 33
Gastrointestinal disorders Dry mouth	18.3% 95/518 • Number of events 98	14.0% 36/258 • Number of events 38
Gastrointestinal disorders Dyspepsia	6.4% 33/518 • Number of events 34	6.2% 16/258 • Number of events 16
Gastrointestinal disorders Flatulence	4.6% 24/518 • Number of events 24	5.0% 13/258 • Number of events 14
Gastrointestinal disorders Gastrooesophageal reflux disease	9.5% 49/518 • Number of events 49	10.1% 26/258 • Number of events 26
Gastrointestinal disorders Nausea	23.7% 123/518 • Number of events 155	14.3% 37/258 • Number of events 45
General disorders Fatigue	9.5% 49/518 • Number of events 52	7.8% 20/258 • Number of events 24
General disorders Irritability	4.2% 22/518 • Number of events 22	6.2% 16/258 • Number of events 17
Immune system disorders Seasonal allergy	12.5% 65/518 • Number of events 65	13.6% 35/258 • Number of events 35
Infections and infestations Nasopharyngitis	9.1% 47/518 • Number of events 48	7.4% 19/258 • Number of events 24
Infections and infestations Sinusitis	4.4% 23/518 • Number of events 24	7.0% 18/258 • Number of events 19
Infections and infestations Upper respiratory tract infection	7.3% 38/518 • Number of events 42	7.8% 20/258 • Number of events 25
Metabolism and nutrition disorders Hypercholesterolaemia	8.5% 44/518 • Number of events 44	7.8% 20/258 • Number of events 20
Metabolism and nutrition disorders Type 2 diabetes mellitus	1.5% 8/518 • Number of events 8	5.0% 13/258 • Number of events 13
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 39/518 • Number of events 42	7.8% 20/258 • Number of events 21
Musculoskeletal and connective tissue disorders Arthritis	5.4% 28/518 • Number of events 28	3.5% 9/258 • Number of events 9
Musculoskeletal and connective tissue disorders Back pain	15.3% 79/518 • Number of events 85	13.6% 35/258 • Number of events 36
Musculoskeletal and connective tissue disorders Osteoarthritis	5.4% 28/518 • Number of events 29	2.3% 6/258 • Number of events 6
Nervous system disorders Dizziness	11.2% 58/518 • Number of events 68	10.9% 28/258 • Number of events 30
Nervous system disorders Headache	34.2% 177/518 • Number of events 221	32.2% 83/258 • Number of events 96
Nervous system disorders Migraine	9.3% 48/518 • Number of events 51	7.0% 18/258 • Number of events 18
Nervous system disorders Somnolence	4.6% 24/518 • Number of events 25	5.0% 13/258 • Number of events 14
Nervous system disorders Tension headache	4.2% 22/518 • Number of events 25	5.4% 14/258 • Number of events 14
Psychiatric disorders Anxiety	5.2% 27/518 • Number of events 30	9.3% 24/258 • Number of events 28
Psychiatric disorders Insomnia	13.3% 69/518 • Number of events 72	14.7% 38/258 • Number of events 42
Respiratory, thoracic and mediastinal disorders Asthma	8.1% 42/518 • Number of events 43	7.4% 19/258 • Number of events 19
Skin and subcutaneous tissue disorders Hyperhidrosis	5.2% 27/518 • Number of events 27	2.3% 6/258 • Number of events 6
Vascular disorders Hypertension	19.3% 100/518 • Number of events 101	21.7% 56/258 • Number of events 57

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60