Trial Outcomes & Findings for A Study Comparing Duloxetine to Other Antidepressants in the Treatment of Severe Depression (NCT NCT00666757)

NCT ID: NCT00666757

Last Updated: 2010-06-15

Results Overview

Visitwise probability of participants per treatment meeting remission criteria (QIDS-SR total score \[TS\]\</=5 at week 12 endpoint) were estimated using a pseudolikelihood-based mixed-models repeated measures analysis for a categorical outcome, model included fixed, categorical effects of treatment group (duloxetine vs. SSRIs), visit, treatment group-by-visit \& continuous, fixed covariate of baseline QIDS-SR TS, and random effect of participant. Primary analysis contrasted remission probability at week 12 endpoint between treatment groups.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 750 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2010-06-15

Participant Flow

The United States study started in May 2008 and completed in March 2009. A total of 72 sites participated (65 Psychiatric, 5 Family Practice, and 2 Internal Medicine specialties).

Participant milestones

Measure	Duloxetine 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Overall Study STARTED	372	378
Overall Study COMPLETED	272	281
Overall Study NOT COMPLETED	100	97

Reasons for withdrawal

Measure	Duloxetine 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Overall Study Lost to Follow-up	39	35
Overall Study Protocol Violation	23	24
Overall Study Adverse Event	22	12
Overall Study Withdrawal by Subject	13	17
Overall Study Lack of Efficacy	3	6
Overall Study Physician Decision	0	2
Overall Study Sponsor decision	0	1

Baseline Characteristics

A Study Comparing Duloxetine to Other Antidepressants in the Treatment of Severe Depression

Baseline characteristics by cohort

Measure	Duloxetine n=372 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=378 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks	Total n=750 Participants Total of all reporting groups
Age Continuous	44.3 years STANDARD_DEVIATION 13.01 • n=5 Participants	43.8 years STANDARD_DEVIATION 13.05 • n=7 Participants	44.1 years STANDARD_DEVIATION 13.02 • n=5 Participants
Sex: Female, Male Female	237 Participants n=5 Participants	259 Participants n=7 Participants	496 Participants n=5 Participants
Sex: Female, Male Male	135 Participants n=5 Participants	119 Participants n=7 Participants	254 Participants n=5 Participants
Race/Ethnicity, Customized African Descent	76 participants n=5 Participants	68 participants n=7 Participants	144 participants n=5 Participants
Race/Ethnicity, Customized Caucasian	231 participants n=5 Participants	241 participants n=7 Participants	472 participants n=5 Participants
Race/Ethnicity, Customized East/Southeast Asian	2 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	59 participants n=5 Participants	52 participants n=7 Participants	111 participants n=5 Participants
Race/Ethnicity, Customized Western Asian	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	7 participants n=7 Participants	10 participants n=5 Participants
Race/Ethnicity, Customized Missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	372 participants n=5 Participants	378 participants n=7 Participants	750 participants n=5 Participants
History, Met Diagnosis of Major Mood Disorder (MDD)	372 participants n=5 Participants	378 participants n=7 Participants	750 participants n=5 Participants
17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale Score	7.45 units on a scale STANDARD_DEVIATION 2.22 • n=5 Participants	7.42 units on a scale STANDARD_DEVIATION 2.25 • n=7 Participants	7.43 units on a scale STANDARD_DEVIATION 2.23 • n=5 Participants
17-Item Hamilton Depression Rating Scale (HAMD-17) Bech Subscale Score	12.97 units on a scale STANDARD_DEVIATION 2.13 • n=5 Participants	13.13 units on a scale STANDARD_DEVIATION 1.95 • n=7 Participants	13.05 units on a scale STANDARD_DEVIATION 2.04 • n=5 Participants
17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale Score	12.47 units on a scale STANDARD_DEVIATION 2.33 • n=5 Participants	12.48 units on a scale STANDARD_DEVIATION 2.22 • n=7 Participants	12.47 units on a scale STANDARD_DEVIATION 2.27 • n=5 Participants
17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation Subscale	8.36 units on a scale STANDARD_DEVIATION 1.55 • n=5 Participants	8.53 units on a scale STANDARD_DEVIATION 1.54 • n=7 Participants	8.45 units on a scale STANDARD_DEVIATION 1.55 • n=5 Participants
17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale Score	4.73 units on a scale STANDARD_DEVIATION 1.35 • n=5 Participants	4.77 units on a scale STANDARD_DEVIATION 1.33 • n=7 Participants	4.75 units on a scale STANDARD_DEVIATION 1.34 • n=5 Participants
17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score	25.03 units on a scale STANDARD_DEVIATION 4.44 • n=5 Participants	25.03 units on a scale STANDARD_DEVIATION 4.24 • n=7 Participants	25.03 units on a scale STANDARD_DEVIATION 4.34 • n=5 Participants
Brief Pain Inventory (BPI) Average 24-Hour Pain Score	2.64 units on a scale STANDARD_DEVIATION 2.74 • n=5 Participants	2.98 units on a scale STANDARD_DEVIATION 2.79 • n=7 Participants	2.81 units on a scale STANDARD_DEVIATION 2.77 • n=5 Participants
History, Age at First Episode	31.53 years STANDARD_DEVIATION 14.39 • n=5 Participants	30.42 years STANDARD_DEVIATION 14.30 • n=7 Participants	30.97 years STANDARD_DEVIATION 14.34 • n=5 Participants
History, Number of Previous MDD Episodes	6.74 episodes STANDARD_DEVIATION 15.32 • n=5 Participants	5.09 episodes STANDARD_DEVIATION 11.08 • n=7 Participants	5.91 episodes STANDARD_DEVIATION 13.37 • n=5 Participants
History, Time Since Most Recent MDD Episode	11.76 months STANDARD_DEVIATION 19.06 • n=5 Participants	11.92 months STANDARD_DEVIATION 30.69 • n=7 Participants	11.84 months STANDARD_DEVIATION 25.57 • n=5 Participants
Quick Inventory of Depressive Symptomatology (QIDS-SR) Total Score	21.64 units on a scale STANDARD_DEVIATION 1.71 • n=5 Participants	21.70 units on a scale STANDARD_DEVIATION 1.70 • n=7 Participants	21.67 units on a scale STANDARD_DEVIATION 1.701 • n=5 Participants
Sheehan Disability Scale (SDS) Global Functional Impairment Score	22.70 units on a scale STANDARD_DEVIATION 5.52 • n=5 Participants	22.72 units on a scale STANDARD_DEVIATION 6.05 • n=7 Participants	22.71 units on a scale STANDARD_DEVIATION 5.79 • n=5 Participants
Sheehan Disability Scale (SDS) Item 1: Symptoms Disrupted Work/School	7.00 units on a scale STANDARD_DEVIATION 2.40 • n=5 Participants	7.09 units on a scale STANDARD_DEVIATION 2.45 • n=7 Participants	7.05 units on a scale STANDARD_DEVIATION 2.42 • n=5 Participants
Sheehan Disability Scale (SDS) Item 2: Symptoms Disrupted Social Life/Leisure Activities	7.81 units on a scale STANDARD_DEVIATION 1.97 • n=5 Participants	7.82 units on a scale STANDARD_DEVIATION 2.13 • n=7 Participants	7.82 units on a scale STANDARD_DEVIATION 2.05 • n=5 Participants
Sheehan Disability Scale (SDS) Item 3: Symptoms Disrupted Family Life/Home Responsibilities	7.67 units on a scale STANDARD_DEVIATION 2.02 • n=5 Participants	7.68 units on a scale STANDARD_DEVIATION 2.28 • n=7 Participants	7.67 units on a scale STANDARD_DEVIATION 2.15 • n=5 Participants
Weight	86.62 kilograms (kg) STANDARD_DEVIATION 22.37 • n=5 Participants	86.23 kilograms (kg) STANDARD_DEVIATION 23.97 • n=7 Participants	86.42 kilograms (kg) STANDARD_DEVIATION 23.18 • n=5 Participants
World Health Organization Health and Work Performance Questionnaire (HPQ), Absolute Absenteeism	28.64 hours lost per week STANDARD_DEVIATION 59.28 • n=5 Participants	33.29 hours lost per week STANDARD_DEVIATION 72.90 • n=7 Participants	31.00 hours lost per week STANDARD_DEVIATION 66.48 • n=5 Participants
World Health Organization Health and Work Performance Questionnaire (HPQ), Absolute Presenteeism	48.85 units on a scale STANDARD_DEVIATION 22.47 • n=5 Participants	50.63 units on a scale STANDARD_DEVIATION 23.86 • n=7 Participants	49.74 units on a scale STANDARD_DEVIATION 23.16 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=366, SSRI N=371; and Week 12: Duloxetine N=273, SSRI N=284

Visitwise probability of participants per treatment meeting remission criteria (QIDS-SR total score [TS]</=5 at week 12 endpoint) were estimated using a pseudolikelihood-based mixed-models repeated measures analysis for a categorical outcome, model included fixed, categorical effects of treatment group (duloxetine vs. SSRIs), visit, treatment group-by-visit & continuous, fixed covariate of baseline QIDS-SR TS, and random effect of participant. Primary analysis contrasted remission probability at week 12 endpoint between treatment groups.

Outcome measures

Measure	Duloxetine n=273 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Probability of Remission [16-item Quick Inventory of Depressive Symptomatology (QIDS-SR) Score Less Than or Equal to 5 at 12-Week Endpoint]	0.36 Probability of remission Standard Error 0.03	0.32 Probability of remission Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=366, SSRI N=371; and Week 12: Duloxetine N=273, SSRI N=284

The QIDS-SR is a 16-item, participant-rated short form of the Inventory of Depressive Symptomatology that assesses 9 domains: sad mood, concentration, self-outlook, suicidal ideation, involvement, energy/fatigability, sleep disturbance, appetite/weight increase/decrease and psychomotor agitation/retardation. Scores range from 0 (none) to 27 (very severe). The QIDS-SR total score was used to derive the mean change from baseline to endpoint depression.

Outcome measures

Measure	Duloxetine n=273 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in QIDS-SR Total Score at 12-Week Endpoint (Mood Measure)	-13.4 units on a scale Standard Error 0.36	-12.6 units on a scale Standard Error 0.35

SECONDARY outcome

Timeframe: 12 weeks

Population: Intent to treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=365, SSRI N=371 and Week 12: Duloxetine N=272, SSRI N=283

Visitwise percentages of participants meeting remission criteria HAMD-17 total score [TS] </=7 at week 12 endpoint) were estimated using a categorical, pseudolike-lihood-based repeated measures approach, & included fixed, categorical effects of treatment group (duloxetine vs. SSRIs), visit, treatment group-by-visit interaction, & continuous, fixed covariate of baseline HAMD-17 TS. Primary analysis will be contrast of remission rates at week 12 endpoint between treatment groups, & represents estimated remission rates for each treatment group had all participants completed 12 weeks of therapy.

Outcome measures

Measure	Duloxetine n=272 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=283 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Probability of Remission [17-item Hamilton Depression Rating Scale (HAMD-17) (Mood Measure) Less Than or Equal to 7 at 12-Week Endpoint]	0.53 Probability of remission Standard Error 0.03	0.44 Probability of remission Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline, 12-Weeks

Population: Intent to treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=366, SSRI N=371; and Week 12: Duloxetine N=273, SSRI N=284

Visitwise percentages of participants meeting response criteria (50% reduction from baseline QIDS-SR total score at 12-week endpoint) were estimated using a categorical, pseudolikelihood-based repeated measures approach, & included fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, & continuous, fixed covariate of baseline QIDS-SR. The primary analysis will be the contrast of response rates at week 12 endpoint between treatment groups, and represents estimated response rates for each treatment group had all participants completed 12 weeks of therapy.

Outcome measures

Measure	Duloxetine n=273 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Probability of Response [QIDS-SR Total Score (Mood Measure) Greater Than Or Equal To 50 Percent Reduction From Baseline To 12 Week Endpoint]	0.71 Probability of response Standard Error 0.03	0.64 Probability of response Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline, 12-Weeks

Population: Intent to treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=365, SSRI N=371; and Week 12: Duloxetine N=272, SSRI N=283

Visitwise percentages of participants meeting response criteria 50% reduction from baseline in HAMD-17 total score at 12-Week endpoint) were estimated using a categorical, pseudolike-lihood-based repeated measures approach, & included fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, & continuous, fixed covariate of baseline HAMD-17 TS. Primary analysis will be the contrast of response rates at week 12 endpoint between treatment groups, & represents estimated response rates for each treatment group had all participants completed 12 weeks of therapy.

Outcome measures

Measure	Duloxetine n=272 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=283 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Probability of Response [HAMD-17 Total Score (Mood Measure) Greater Than Or Equal To 50 Percent Reduction From Baseline To 12 Week Endpoint]	0.73 Probability of response Standard Error 0.03	0.61 Probability of response Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=365, SSRI N=371; and; and Week 12: Duloxetine N=272, SSRI N=283

The HAMD-17 is a rater-administered assessment of depression severity and improvement, with total score ranges from 0 (not at all depressed) to 52 (most severely depressed).

Outcome measures

Measure	Duloxetine n=272 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=283 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in HAMD-17 Total Score at 12-Week Endpoint (Mood Measure)	-17.03 units on a scale Standard Error 0.43	-15.3 units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=367, SSRI N=371; and Week 12: Duloxetine N=274, SSRI N=284

HAMD-17 subscale consists of items 10, 11, 12, 13, 15, and 17 evaluates agitation, and severity of psychic and somatic manifestations of anxiety. Total subscale scores range from 0 (normal) to 18 (severe). Mean change from baseline to endpoint.

Outcome measures

Measure	Duloxetine n=274 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score at 12-Week Endpoint (Mood Measure)	-4.89 units on a scale Standard Error 0.16	-4.24 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=367, SSRI N=371; and Week 12: Duloxetine N=274, SSRI N=284

HAMD-17 Maier Subscale consists of Items 1, 2, 7, 8, 9, 10 and represents the "core" symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe).

Outcome measures

Measure	Duloxetine n=274 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in HAMD-17 Maier Subscale Score at 12-Week Endpoint (Mood Measure)	-9.01 units on a scale Standard Error 0.23	-8.16 units on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=367, SSRI N=371; and Week 12: Duloxetine N=274; SSRI N=284

HAMD-17 Bech subscale consists of items 1, 2, 7, 8, 10, and 13 used to evaluate core symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe).

Outcome measures

Measure	Duloxetine n=274 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in HAMD-17 Bech Subscale Score at 12-Week Endpoint (Mood Measure)	-9.21 units on a scale Standard Error 0.24	-8.40 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=366, SSRI N=371; and Week 12: Duloxetine N=273, SSRI N=284

The HAMD-17 Retardation subscale consists of Items 1, 7, 8, 14 and evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation. Total subscale scores range from 0 (normal) to 14 (severe).

Outcome measures

Measure	Duloxetine n=273 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in HAMD-17 Retardation Subscale Score at 12-Week Endpoint (Mood Measure)	-5.99 units on a scale Standard Error 0.16	-5.49 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=367, SSRI N=371; and Week 12: Duloxetine N=274, SSRI N=285

The HAMD-17 Sleep Subscale consists of Items 4, 5, 6 and evaluates initial, middle, and late insomnia. Total subscale scores range from 0 (no difficulty) to 6 (difficulty).

Outcome measures

Measure	Duloxetine n=274 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=285 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in HAMD-17 Sleep Subscale Score at 12-Week Endpoint (Mood Measure)	-2.77 units on a scale Standard Error 0.12	-2.58 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=211, SSRI N=233; and Week 12: Duloxetine N=156, N=166

The BPI is a self-reported scale measuring pain severity and pain-specific interference on function on a scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The BPI average 24-hour pain measure was used to derive the overall mean change from baseline to endpoint, in those participants who had a BPI average 24-hour pain score of 3 or greater at baseline.

Outcome measures

Measure	Duloxetine n=156 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=166 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in Brief Pain Inventory (BPI) Average 24-hour Pain Score, in Particpants With a Baseline BPI Average 24-hour Pain Score of 3 or Greater, at 12-Week Endpoint (Pain Measure)	-2.95 units on a scale Standard Error 0.21	-2.39 units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=346, SSRI N=348; and Week 12: Duloxetine N=249, SSRI N=257

The BPI is a self-reported scale measuring pain severity and pain-specific interference on function, with scores ranging from 0 (does not interfere) to 10 (completely interferes). The BPI average 24-hour pain measure was used to derive the overall mean change from baseline to endpoint.

Outcome measures

Measure	Duloxetine n=249 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=257 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in BPI Average 24 Hour Pain Score at 12-Week Endpoint (Pain Measure)	-1.83 units on a scale Standard Error 0.15	-1.43 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=362, SSRI N=370; and Week 12: Duloxetine N=270, SSRI N=283

The SDS is a participant-rated anchored visual analog scale to assess disability across the three domains of work/school, social life, and family life, with each item scored from 0 (not at all) to 10 (very severely), with a summarization of the 3 items to evaluate global functioning. The Global Functional Impairment Score is a total score score that ranges from 0 (unimpaired) to 30 (highly impaired), and was used to derived the mean change from baseline to endpoint.

Outcome measures

Measure	Duloxetine n=270 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=283 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment Score at 12-Week Endpoint (Functional Outcome Measure)	-13.56 units on a scale Standard Error 0.53	-11.53 units on a scale Standard Error 0.52

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=260,SSRI N=267; and Week 12: Duloxetine N=182, SSRI N=192

The SDS is completed by the participant and Item 1 is used to assess the effect of the participant's symptoms on their work/school schedule. Scores range from 0 to 10 with higher values indicating greater disruption in the participant's work/school life.

Outcome measures

Measure	Duloxetine n=182 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=192 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in SDS Work/School Item Score at 12-Week Endpoint (Functional Outcome Measure)	-4.52 units on a scale Standard Error 0.22	-3.85 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=363, SSRI N=370; and Week 12: Duloxetine N=271, SSRI N=283

The SDS is completed by the participant and Item 3 is used to assess the effect of the participant's symptoms on their family life/home responsibilities. Scores range from 0 to 10 with higher values indicating greater disruption in the participant's family life/home responsibilities.

Outcome measures

Measure	Duloxetine n=271 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=283 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in Sheehan Disability Scale (SDS) Family/Home Item Score at Week-12 Endpoint (Functional Outcome Measure)	-4.51 units on a scale Standard Error 0.19	-3.94 units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=362, SSRI N=370; and Week 12: Duloxetine N=270, SSRI N=283

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

Outcome measures

Measure	Duloxetine n=270 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=283 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in SDS Social Item Score at 12-Week Endpoint (Functional Outcome Measure)	-4.69 units on a scale Standard Error 0.18	-4.04 units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=367, SSRI N=371; and Week 12: Duloxetine N=274, SSRI N=285

Mean change from baseline to endpoint in systolic blood pressure

Outcome measures

Measure	Duloxetine n=274 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=285 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in Systolic Blood Pressure at Week-12 Endpoint	0.58 millimeters of mmercury (mmHg) Standard Error 0.69	0.55 millimeters of mmercury (mmHg) Standard Error 0.68

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=367, SSRI N=371: and Week 12: Duloxetine N=274, SSRI N=285

Mean change from baseline to endpoint in diastolic blood pressure

Outcome measures

Measure	Duloxetine n=274 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=285 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in Diastolic Blood Pressure at Week-12 Endpoint	-0.14 mmHg Standard Error 0.48	0.45 mmHg Standard Error 0.46

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=367, SSRI N=371; and Week 12: Duloxetine N=274, SSRI N=285

Mean change from baseline to endpoint in pulse rate

Outcome measures

Measure	Duloxetine n=274 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=285 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in Pulse Rate at Week-12 Endpoint	2.74 beats per minute (bpm) Standard Error 0.58	0.47 beats per minute (bpm) Standard Error 0.57

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Data based on number of subjects enrolled at Week 0: Duloxetine N=366, SSRI N=370; and Week 12: Duloxetine N=273, SSRI N=284

Mean change from baseline to endpoint in weight

Outcome measures

Measure	Duloxetine n=273 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=284 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in Weight at Week-12 Endpoint	-0.32 kilograms (kg) Standard Error 0.18	-0.17 kilograms (kg) Standard Error 0.18

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Last Observation Carried Forward.

WP score was calculated by taking midpoint of annual before-tax income reported on HPQ. A multiplier of 1.25 produced estimated direct & indirect (i.e. benefits) income. Annual hours expected to work were calculated from expected daily work hours, multiplied by 236 days. Hourly, indirect income was total direct + indirect income, divided by # of expected annual work hours. Indirect hours lost annually for WP=hours expected to be worked annually times WP percent, times hourly rate=dollars earned, and then subtracted from total direct + indirect income=dollars lost annually due to WP.

Outcome measures

Measure	Duloxetine n=130 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=132 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in World Health Organization Health and Work Performance Questionnaire, Clinical Trials 7-Day Version (HPQ), Dollars of Income Lost Due to Work Presenteeism (WP)Score, at Week-12 Endpoint	7250.93 dollars Standard Error 954.77	5074.09 dollars Standard Error 957.77

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 12 weeks

Population: Intent to Treat. Last Observation Carried Forward.

Self-administered assessment used to determine a participant's work performance in terms of employment status, absenteeism if employed, productivity while at work, usual occupation, and annual income. Tool assesses the potential impact of change in depressive symptoms on work productivity and its associated employer costs. Scale ranges from 0 to 100% of work days in past 30 days. Absenteeism and presenteeism were combined into a measure of total lost work performance by adding absenteeism to the value ([100-absenteeism] × [100-presenteeism]). Mean change baseline to endpoint.

Outcome measures

Measure	Duloxetine n=134 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=142 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in World Health Organization Health and Work Performance Questionnaire, Clinical Trials 7-Day Version (HPQ), Dollars of Income Lost Due to Work Absenteeism Score at Week-12 Endpoint	-3978.98 dollars Standard Error 1708.92	-1932.46 dollars Standard Error 1689.85

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Last Observation Carried Forward.

Self-administered assessment used to determine a subject's work performance in terms of employment status, absenteeism if employed, productivity while at work, usual occupation, and annual income. Tool assesses the potential impact of change in depressive symptoms on work productivity and its associated employer costs. Defined on a 0-100 scale for the percentage of work days the respondent missed in the past 30 days. Absolute absenteeism: actual hours worked minus expected hours equals number of missed work days. Mean change baseline to endpoint is reported.

Outcome measures

Measure	Duloxetine n=137 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=146 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in World Health Organization Health and Work Performance Questionnaire, Clinical Trials 7-Day Version (HPQ), Absenteeism at 12-Week Endpoint	-9.56 hours lost per week Standard Error 5.14	0.41 hours lost per week Standard Error 5.05

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 12 Weeks

Population: Intent to Treat. Last Observation Carried Forward.

Self-administered assessment used to determine a participant's work performance (employment status, absenteeism if employed, productivity while at work, usual occupation, & annual income). Tool assesses the potential impact of change in depressive symptoms on work productivity & its associated employer costs using a 0-100 scale in which 0 meant doing no work at all on days spent at work and 100 meant performing at the level of a top worker. Absolute presenteeism: difference between "score for self" and "score for average worker in same job". Mean change baseline to endpoint is reported.

Outcome measures

Measure	Duloxetine n=136 Participants 30-120 milligrams (mgs) orally daily for 12 weeks	Selective Serotonin Reuptake Inhibitor (SSRI) n=139 Participants all comparator SSRIs pooled together: citalopram 20-40 mgs orally daily for 12 weeks; fluoxetine 20-80 mg orally daily for 12 weeks; paroxetine 20-50 mgs orally daily for 12 weeks; and sertraline 50-200 mgs orally daily for 12 weeks
Change From Baseline in World Health Organization Health and Work Performance Questionnaire, Clinical Trials 7-Day Version (HPQ), Presenteeism Score, at Week-12 Endpoint	24.56 units on a scale Standard Error 2.14	20.73 units on a scale Standard Error 2.11

Adverse Events

Duloxetine

Serious events: 4 serious events

Other events: 277 other events

Deaths: 0 deaths

Citalopram

Serious events: 2 serious events

Other events: 112 other events

Deaths: 0 deaths

Fluoxetine

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

Paroxetine

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

Sertraline

Serious events: 2 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Measure	Duloxetine n=372 participants at risk 30-120 mg orally daily for 12 weeks	Citalopram n=157 participants at risk 20-40 mg orally daily for 12 weeks	Fluoxetine n=57 participants at risk 20-80 mg orally daily for 12 weeks	Paroxetine n=45 participants at risk 20-50 mg orally daily for 12 weeks	Sertraline n=119 participants at risk 50-200 mg orally daily for 12 weeks
Infections and infestations Pneumonia	0.00% 0/372	0.64% 1/157 • Number of events 1	0.00% 0/57	0.00% 0/45	0.00% 0/119
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/372	0.00% 0/157	0.00% 0/57	0.00% 0/45	0.84% 1/119 • Number of events 1
Injury, poisoning and procedural complications Tibia fracture	0.27% 1/372 • Number of events 1	0.00% 0/157	0.00% 0/57	0.00% 0/45	0.00% 0/119
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/372	0.00% 0/157	0.00% 0/57	2.2% 1/45 • Number of events 1	0.00% 0/119
Nervous system disorders Cerebrovascular accident	0.00% 0/372	0.00% 0/157	1.8% 1/57 • Number of events 1	0.00% 0/45	0.00% 0/119
Nervous system disorders Temporal lobe epilepsy	0.27% 1/372 • Number of events 1	0.00% 0/157	0.00% 0/57	0.00% 0/45	0.00% 0/119
Psychiatric disorders Post-traumatic stress disorder	0.00% 0/372	0.00% 0/157	0.00% 0/57	0.00% 0/45	0.84% 1/119 • Number of events 1
Psychiatric disorders Suicidal ideation	0.27% 1/372 • Number of events 1	0.00% 0/157	0.00% 0/57	0.00% 0/45	0.00% 0/119
Renal and urinary disorders Nephrolithiasis	0.27% 1/372 • Number of events 1	0.00% 0/157	0.00% 0/57	0.00% 0/45	0.00% 0/119
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/372	0.64% 1/157 • Number of events 1	0.00% 0/57	0.00% 0/45	0.00% 0/119

Other adverse events

Measure	Duloxetine n=372 participants at risk 30-120 mg orally daily for 12 weeks	Citalopram n=157 participants at risk 20-40 mg orally daily for 12 weeks	Fluoxetine n=57 participants at risk 20-80 mg orally daily for 12 weeks	Paroxetine n=45 participants at risk 20-50 mg orally daily for 12 weeks	Sertraline n=119 participants at risk 50-200 mg orally daily for 12 weeks
Gastrointestinal disorders Constipation	8.9% 33/372 • Number of events 35	5.1% 8/157 • Number of events 8	1.8% 1/57 • Number of events 2	4.4% 2/45 • Number of events 2	2.5% 3/119 • Number of events 3
Gastrointestinal disorders Diarrhoea	9.7% 36/372 • Number of events 41	10.8% 17/157 • Number of events 18	17.5% 10/57 • Number of events 10	6.7% 3/45 • Number of events 3	15.1% 18/119 • Number of events 20
Gastrointestinal disorders Dry mouth	17.7% 66/372 • Number of events 67	10.2% 16/157 • Number of events 16	19.3% 11/57 • Number of events 11	8.9% 4/45 • Number of events 4	10.9% 13/119 • Number of events 13
Gastrointestinal disorders Nausea	16.9% 63/372 • Number of events 70	10.8% 17/157 • Number of events 18	14.0% 8/57 • Number of events 9	17.8% 8/45 • Number of events 8	12.6% 15/119 • Number of events 16
General disorders Fatigue	7.3% 27/372 • Number of events 28	6.4% 10/157 • Number of events 10	3.5% 2/57 • Number of events 3	17.8% 8/45 • Number of events 8	2.5% 3/119 • Number of events 3
Infections and infestations Nasopharyngitis	3.0% 11/372 • Number of events 11	3.2% 5/157 • Number of events 5	1.8% 1/57 • Number of events 2	8.9% 4/45 • Number of events 4	4.2% 5/119 • Number of events 5
Infections and infestations Upper respiratory tract infection	2.7% 10/372 • Number of events 10	5.1% 8/157 • Number of events 8	3.5% 2/57 • Number of events 2	2.2% 1/45 • Number of events 1	4.2% 5/119 • Number of events 5
Metabolism and nutrition disorders Decreased appetite	4.8% 18/372 • Number of events 18	3.2% 5/157 • Number of events 5	7.0% 4/57 • Number of events 4	0.00% 0/45	0.84% 1/119 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	1.3% 5/372 • Number of events 6	1.9% 3/157 • Number of events 5	5.3% 3/57 • Number of events 3	4.4% 2/45 • Number of events 2	1.7% 2/119 • Number of events 2
Musculoskeletal and connective tissue disorders Back pain	2.7% 10/372 • Number of events 13	2.5% 4/157 • Number of events 4	5.3% 3/57 • Number of events 3	2.2% 1/45 • Number of events 1	1.7% 2/119 • Number of events 2
Nervous system disorders Dizziness	6.2% 23/372 • Number of events 26	2.5% 4/157 • Number of events 4	1.8% 1/57 • Number of events 1	11.1% 5/45 • Number of events 5	5.9% 7/119 • Number of events 7
Nervous system disorders Headache	14.8% 55/372 • Number of events 62	10.2% 16/157 • Number of events 18	14.0% 8/57 • Number of events 11	13.3% 6/45 • Number of events 6	13.4% 16/119 • Number of events 19
Nervous system disorders Somnolence	7.3% 27/372 • Number of events 27	7.0% 11/157 • Number of events 11	3.5% 2/57 • Number of events 2	6.7% 3/45 • Number of events 3	2.5% 3/119 • Number of events 3
Psychiatric disorders Anorgasmia	1.1% 4/372 • Number of events 4	1.9% 3/157 • Number of events 3	1.8% 1/57 • Number of events 1	6.7% 3/45 • Number of events 3	0.00% 0/119
Psychiatric disorders Insomnia	6.7% 25/372 • Number of events 25	1.9% 3/157 • Number of events 3	14.0% 8/57 • Number of events 9	6.7% 3/45 • Number of events 3	3.4% 4/119 • Number of events 4
Skin and subcutaneous tissue disorders Hyperhidrosis	3.2% 12/372 • Number of events 13	0.64% 1/157 • Number of events 1	5.3% 3/57 • Number of events 3	6.7% 3/45 • Number of events 3	5.0% 6/119 • Number of events 6

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