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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Depression
Interventions:	Drug: duloxetine Drug: fluoxetine Drug: citalopram Drug: paroxetine Drug: sertraline

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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).

	Duloxetine	Selective Serotonin Reuptake Inhibitor (SSRI)
STARTED	372	378
COMPLETED	272	281
NOT COMPLETED	100	97
Lost to Follow-up	39	35
Protocol Violation	23	24
Adverse Event	22	12
Withdrawal by Subject	13	17
Lack of Efficacy	3	6
Physician Decision	0	2
Sponsor decision	0	1

Baseline Characteristics

Reporting Groups

	Description
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

Baseline Measures

	Duloxetine	Selective Serotonin Reuptake Inhibitor (SSRI)	Total
Number of Participants [units: participants]	372	378	750
Age [units: years] Mean ± Standard Deviation	44.3 ± 13.01	43.8 ± 13.05	44.1 ± 13.02
Gender [units: participants]
Female	237	259	496
Male	135	119	254
Race/Ethnicity, Customized [units: participants]
African Descent	76	68	144
Caucasian	231	241	472
East/Southeast Asian	2	7	9
Hispanic	59	52	111
Western Asian	1	2	3
Other	3	7	10
Missing	0	1	1
Region of Enrollment ^[1] [units: participants]
United States	372	378	750
History, Met Diagnosis of Major Mood Disorder (MDD) [units: participants]	372	378	750
17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale Score ^[2] [units: units on a scale] Mean ± Standard Deviation	7.45 ± 2.22	7.42 ± 2.25	7.43 ± 2.23
17-Item Hamilton Depression Rating Scale (HAMD-17) Bech Subscale Score ^[3] [units: units on a scale] Mean ± Standard Deviation	12.97 ± 2.13	13.13 ± 1.95	13.05 ± 2.04
17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale Score ^[4] [units: units on a scale] Mean ± Standard Deviation	12.47 ± 2.33	12.48 ± 2.22	12.47 ± 2.27
17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation Subscale ^[5] [units: units on a scale] Mean ± Standard Deviation	8.36 ± 1.55	8.53 ± 1.54	8.45 ± 1.55
17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale Score ^[6] [units: units on a scale] Mean ± Standard Deviation	4.73 ± 1.35	4.77 ± 1.33	4.75 ± 1.34
17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score ^[7] [units: units on a scale] Mean ± Standard Deviation	25.03 ± 4.44	25.03 ± 4.24	25.03 ± 4.34
Brief Pain Inventory (BPI) Average 24-Hour Pain Score ^[8] [units: units on a scale] Mean ± Standard Deviation	2.64 ± 2.74	2.98 ± 2.79	2.81 ± 2.77
History, Age at First Episode ^[9] [units: years] Mean ± Standard Deviation	31.53 ± 14.39	30.42 ± 14.30	30.97 ± 14.34
History, Number of Previous MDD Episodes ^[10] [units: episodes] Mean ± Standard Deviation	6.74 ± 15.32	5.09 ± 11.08	5.91 ± 13.37
History, Time Since Most Recent MDD Episode ^[11] [units: months] Mean ± Standard Deviation	11.76 ± 19.06	11.92 ± 30.69	11.84 ± 25.57
Quick Inventory of Depressive Symptomatology (QIDS-SR) Total Score ^[12] [units: units on a scale] Mean ± Standard Deviation	21.64 ± 1.71	21.70 ± 1.70	21.67 ± 1.701
Sheehan Disability Scale (SDS) Global Functional Impairment Score ^[13] [units: units on a scale] Mean ± Standard Deviation	22.70 ± 5.52	22.72 ± 6.05	22.71 ± 5.79
Sheehan Disability Scale (SDS) Item 1: Symptoms Disrupted Work/School ^[14] [units: units on a scale] Mean ± Standard Deviation	7.00 ± 2.40	7.09 ± 2.45	7.05 ± 2.42
Sheehan Disability Scale (SDS) Item 2: Symptoms Disrupted Social Life/Leisure Activities ^[15] [units: units on a scale] Mean ± Standard Deviation	7.81 ± 1.97	7.82 ± 2.13	7.82 ± 2.05
Sheehan Disability Scale (SDS) Item 3: Symptoms Disrupted Family Life/Home Responsibilities ^[16] [units: units on a scale] Mean ± Standard Deviation	7.67 ± 2.02	7.68 ± 2.28	7.67 ± 2.15
Weight [units: kilograms (kg)] Mean ± Standard Deviation	86.62 ± 22.37	86.23 ± 23.97	86.42 ± 23.18
World Health Organization Health and Work Performance Questionnaire (HPQ), Absolute Absenteeism ^[17] [units: hours lost per week] Mean ± Standard Deviation	28.64 ± 59.28	33.29 ± 72.90	31.00 ± 66.48
World Health Organization Health and Work Performance Questionnaire (HPQ), Absolute Presenteeism ^[18] [units: units on a scale] Mean ± Standard Deviation	48.85 ± 22.47	50.63 ± 23.86	49.74 ± 23.16

[1]	United States study
[2]	HAMD-17 Anxiety/Somatization 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).
[3]	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).
[4]	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).
[5]	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).
[6]	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).
[7]	The HAMD-17 Total Score 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).
[8]	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).
[9]	Age when first MDD episode occurred
[10]	Number of previous MDD episodes
[11]	Number of months since most recent MDD episode
[12]	The QIDS-SR Total Score 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) depression.
[13]	The SDS Global Functional Impairment Score is a total score that is calculated by summing the SDS Item 1, 2, and 3; the score ranges from 0 (unimpaired) to 30 (highly impaired).
[14]	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.
[15]	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.
[16]	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.
[17]	The HPQ was used to assess the total hours of missed work (absenteeism) per week. The calculation for absolute absenteeism is actual hours worked minus expected hours equals number of missed work days.
[18]	The HPQ was used to assess the participant's performance at work. Participants rated their overall performance on the days worked in the last week on a scale of 0 (worst performance) to 10 (top performance). Values were then multiplied by 10 to create a percentage scale between 0 and 100 percent. Absolute presenteeism equals the difference between the "score for self" and "score for average worker in same job".

Outcome Measures

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1. Primary:

Probability of Remission [16-item Quick Inventory of Depressive Symptomatology (QIDS-SR) Score Less Than or Equal to 5 at 12-Week Endpoint] [ Time Frame: 12 weeks ]

Show Outcome Measure 1

2. Secondary:

Change From Baseline in QIDS-SR Total Score at 12-Week Endpoint (Mood Measure) [ Time Frame: Baseline, 12 weeks ]

Show Outcome Measure 2

3. Secondary:

Probability of Remission [17-item Hamilton Depression Rating Scale (HAMD-17) (Mood Measure) Less Than or Equal to 7 at 12-Week Endpoint] [ Time Frame: 12 weeks ]

Show Outcome Measure 3

4. Secondary:

Probability of Response [QIDS-SR Total Score (Mood Measure) Greater Than Or Equal To 50 Percent Reduction From Baseline To 12 Week Endpoint] [ Time Frame: Baseline, 12-Weeks ]

Show Outcome Measure 4

5. Secondary:

Probability of Response [HAMD-17 Total Score (Mood Measure) Greater Than Or Equal To 50 Percent Reduction From Baseline To 12 Week Endpoint] [ Time Frame: Baseline, 12-Weeks ]

Show Outcome Measure 5

6. Secondary:

Change From Baseline in HAMD-17 Total Score at 12-Week Endpoint (Mood Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 6

7. Secondary:

Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score at 12-Week Endpoint (Mood Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 7

8. Secondary:

Change From Baseline in HAMD-17 Maier Subscale Score at 12-Week Endpoint (Mood Measure) [ Time Frame: Baseline, 12 weeks ]

Show Outcome Measure 8

9. Secondary:

Change From Baseline in HAMD-17 Bech Subscale Score at 12-Week Endpoint (Mood Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 9

10. Secondary:

Change From Baseline in HAMD-17 Retardation Subscale Score at 12-Week Endpoint (Mood Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 10

11. Secondary:

Change From Baseline in HAMD-17 Sleep Subscale Score at 12-Week Endpoint (Mood Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 11

12. Secondary:

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) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 12

13. Secondary:

Change From Baseline in BPI Average 24 Hour Pain Score at 12-Week Endpoint (Pain Measure) [ Time Frame: Baseline, 12 weeks ]

Show Outcome Measure 13

14. Secondary:

Change From Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment Score at 12-Week Endpoint (Functional Outcome Measure) [ Time Frame: Baseline, 12 weeks ]

Show Outcome Measure 14

15. Secondary:

Change From Baseline in SDS Work/School Item Score at 12-Week Endpoint (Functional Outcome Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 15

16. Secondary:

Change From Baseline in Sheehan Disability Scale (SDS) Family/Home Item Score at Week-12 Endpoint (Functional Outcome Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 16

17. Secondary:

Change From Baseline in SDS Social Item Score at 12-Week Endpoint (Functional Outcome Measure) [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 17

18. Secondary:

Change From Baseline in Systolic Blood Pressure at Week-12 Endpoint [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 18

19. Secondary:

Change From Baseline in Diastolic Blood Pressure at Week-12 Endpoint [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 19

20. Secondary:

Change From Baseline in Pulse Rate at Week-12 Endpoint [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 20

21. Secondary:

Change From Baseline in Weight at Week-12 Endpoint [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 21

22. Other Pre-specified:

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 [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 22

23. Other Pre-specified:

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 [ Time Frame: Baseline, 12 weeks ]

Show Outcome Measure 23

24. Other Pre-specified:

Change From Baseline in World Health Organization Health and Work Performance Questionnaire, Clinical Trials 7-Day Version (HPQ), Absenteeism at 12-Week Endpoint [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 24

25. Other Pre-specified:

Change From Baseline in World Health Organization Health and Work Performance Questionnaire, Clinical Trials 7-Day Version (HPQ), Presenteeism Score, at Week-12 Endpoint [ Time Frame: Baseline, 12 Weeks ]

Show Outcome Measure 25

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979

No publications provided by Eli Lilly and Company

Publications automatically indexed to this study:

Martinez JM, Katon W, Greist JH, Kroenke K, Thase ME, Meyers AL, Edwards SE, Marangell LB, Shoemaker S, Swindle R. A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode. Int Clin Psychopharmacol. 2012 Jan;27(1):17-26.

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00666757 History of Changes
Other Study ID Numbers:	11715, F1J-US-HMFT
Study First Received:	April 23, 2008
Results First Received:	February 16, 2010
Last Updated:	May 12, 2010
Health Authority:	United States: Institutional Review Board