A Study in Participants With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01185340
• Collaborator: (none)
• Enrollment: 1,056
• Locations: 49
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 21.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess whether LY2216684 12 milligrams (mg) or 18 mg flexible dose once daily is superior to placebo once daily in the adjunctive treatment of participants with major depressive disorder (MDD) who are partial responders to their selective serotonin reuptake inhibitor (SSRI) treatment.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: LY2216684; Drug: Placebo; Drug: SSRI	Phase 3

Detailed Description

Following the Confirmation (CF) Phase, participants were randomized to adjunctive LY2216684 or adjunctive placebo if they had <25% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score over the past 3 weeks and a current MADRS total score ≥14. Participants who did not meet criteria received adjunctive placebo to preserve the blind.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1056 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Placebo-Controlled, Double-Blind Study of LY2216684 Flexible-Dose 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2216684 + SSRI LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Prior to entering the Adjunctive Treatment (AT) Phase, participants completed a 3-week Confirmation (CF) Phase where they received placebo (administered orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to the LY2216684 treatment arm. For the first 2 weeks of the AT Phase, participants received a starting dose of 12 mg QD. Then, based on efficacy and tolerability, the dose could be increased to 18 mg QD over the next 6 weeks. Participants who had their dose increased to 18 mg QD could have had their dose decreased to 12 mg QD. Participants who completed the AT Phase or discontinued early had the option to enter the Discontinuation (DC) Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.	Drug: LY2216684; Other Names: Edivoxetine ; Drug: Placebo; Drug: SSRI; Participants should have been on their SSRI for at least 6 weeks prior and were to continue on their stable dose throughout the study; Other Names: selective serotonin reuptake inhibitor
Placebo Comparator: Placebo + SSRI Placebo: Administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Prior to entering the Adjunctive Treatment (AT) Phase, participants completed a 3-week Confirmation (CF) Phase where they received placebo (administered orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to the placebo treatment arm. During the AT Phase, participants received placebo (administered orally, QD) adjunctive to their SSRI for 8 weeks. Participants who completed the AT Phase or discontinued early had the option to enter the Discontinuation (DC) Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.	Drug: Placebo; Drug: SSRI; Participants should have been on their SSRI for at least 6 weeks prior and were to continue on their stable dose throughout the study; Other Names: selective serotonin reuptake inhibitor

Outcome Measures

Primary Outcome Measures

1. Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [Randomization, 8 weeks]

   The Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

Secondary Outcome Measures

1. Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Score [Randomization, 8 weeks]

   The Sheehan Disability Scale (SDS) was completed by the participant and used to assess the effect of the participant's symptoms on their work (Item 1), social (Item 2), and family life (Item 3). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. The Global Functional Impairment Score is the sum of the 3 items, and scores ranged from 0 to 30 with higher values indicating greater disruption in the participant's work life (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

2. Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Impact Subscale Score [Randomization, 8 weeks]

   The Fatigue Associated with Depression (FAsD) is a participant-rated scale with a total of 13 items. Six of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Seven of the 13 items ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The impact subscale score was derived by taking the mean of Items 7 through 13 (applicable items only). Item 12 applied only to participants with a spouse or significant other, and Item 13 applied to participants who had a job or who went to school. The FAsD impact subscale score ranges from 1 to 5. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.

3. Probability of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 at Week 8 [8 weeks]

   A Montgomery-Asberg Depression Rating Scale (MADRS) total score of less than or equal to 10 was defined as remission criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). A categorical repeated measures analysis modeled the probability of remission at each visit, and the estimated probabilities were adjusted for treatment, visit, baseline MADRS total score, and treatment-by-visit.

4. Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement [Randomization up to 8 weeks]

   A Montgomery-Asberg Depression Rating Scale (MADRS) total score of less than or equal to 10 for at least 2 consecutive measurements, including the participant's last measurement was defined as remission criteria at last 2 consecutive visits. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Percentage of participants was calculated by dividing the number of participants who meet criteria for remission at last 2 consecutive visits by the total number of participants analyzed, multiplied by 100%.

5. Change From Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score [Randomization, 8 weeks]

   The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression subscale. Scores of 11 or more on either subscale were considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.

6. Probability of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8 [8 weeks]

   A greater than or equal to 50 percent improvement (that is, a decrease from baseline) in the Montgomery-Asberg Depression Rating Scale (MADRS) total score was defined as response criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). A categorical repeated measures analysis modeled the probability of response at each visit, and the estimated probabilities were adjusted for treatment, visit, baseline MADRS total score, and treatment-by-visit.

7. Change From Randomization to Week 8 in The Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score [Randomization, 8 weeks]

   The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression subscale. Scores of 11 or more on either subscale were considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.

8. Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items [Randomization, 8 weeks]

   The Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline item score, treatment-by-visit and baseline item score-by-visit.

9. Change From Randomization to Week 8 in Clinical Global Impressions of Severity (CGI-S) [Randomization, 8 weeks]

   Clinical Global Impression - Severity (CGI-S) measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

10. Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score [Randomization, 8 weeks]

    The Fatigue Associated with Depression (FAsD) is a participant-rated scale with a total of 13 items. Six of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Seven of the 13 items ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score was derived by taking the mean of Items 1 through 6, and the average score was the mean of Items 1 through 13 (derived by taking the mean of all applicable items for each participant). Item 12 applied only to participants with a spouse or significant other, and Item 13 applied to participants who had a job or who went to school. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

11. Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items [Randomization, 8 weeks]

    The Sheehan Disability Scale (SDS) was completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline item score, treatment-by-visit, and baseline item score-by-visit.

12. Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) [Randomization, 8 weeks]

    The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) is a self-administered, 16-item questionnaire measuring degree of enjoyment and satisfaction experienced in various areas of daily life during the past week on a 5-point Likert scale (1=very poor and 5=very good). The total raw score is the sum of Items 1 to 14 and ranges from 14 to 70. The raw scores are converted to and expressed as the percentage of the maximum possible score. Higher scores indicate higher levels of enjoyment/satisfaction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

13. Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D) [Randomization, 8 weeks]

    The EQ-5D Visual Analog Scale is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score is self-reported using a visual analogue scale, marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

14. Percentage of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) [Randomization up to 8 weeks]

    The Columbia-Suicide Severity Rating Scale (C-SSRS) captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation was defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which included a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present at baseline. Percentage of participants was calculated by dividing the number of participants with suicide-related TE events by the total number of participants at risk, multiplied by 100%. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

15. Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale [Randomization, 8 weeks]

    The Arizona Sexual Experiences (ASEX) scale was used to assess sexual functioning in both males and females. The ASEX total score for the male and female version was calculated as the sum of the responses (rated from 1 [extremely] to 6 [no/never]) of the 5 items of the ASEX scale. Total scores ranged from 5 to 30, with higher scores indicating greater sexual dysfunction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

16. Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) [Randomization, 8 weeks]

    The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item was scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total scores ranged from 7 to 42. Higher scores indicate greater disease severity. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

17. Change From Randomization to Week 8 in Blood Pressure [Randomization, 8 weeks]

    Blood pressure measurements were collected when the participant was in a sitting position. Three measurements of sitting blood pressure collected at approximately 1-minute intervals at every visit were averaged and used as the value for the visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.

18. Change From Randomization to Week 8 in Pulse Rate [Randomization, 8 weeks]

    Pulse measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women of child-bearing potential may participate but must test negative for pregnancy at the time of study entry; both women/men agree to use a reliable method of birth control

• Are being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, or fluvoxamine; for at least 6 weeks prior to investigational product dispensing with at least the last 4 weeks at a stable, optimized dose

• Drug and dosage should be within the labeling guidelines for the specific country

• Meet criteria for major depressive disorder (MDD), as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR) criteria

• Meet criteria for partial response, as defined by investigator's opinion that the participant has experienced a minimal clinically meaningful improvement with SSRI

• Have a GRID 17-Item Hamilton Depression Rating Scale (GRID-HAMD17) total score greater than or equal to 16 at screening

• Have less than or equal to 75% improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ)

Exclusion Criteria:

• Have had or currently have any additional ongoing DSM-IV-TR Axis 1 condition other than major depression within 1 year of screening

• Have had any anxiety disorder that was considered a primary diagnosis within the past year (including panic disorder, obsessive-compulsive disorder [OCD], post-traumatic stress disorder [PTSD], generalized anxiety disorder [GAD], and social phobia, but excluding specific phobias)

• Have a current or previous diagnosis of a bipolar disorder, schizophrenia, or other psychotic disorder

• Have a history of substance abuse and/or dependence within the past year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine

• Have an Axis II disorder that, in the judgment of the investigator, would interfere with compliance with protocol

• Unstable medical conditions that contraindicate the use of LY2216684

• Have any diagnosed medical condition that could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, history of urinary hesitancy or retention

• Use of excluded concomitant or psychotropic medication other than SSRI

• Have initiated or discontinued hormone therapy within the 3 months prior to enrollment

• History of treatment-resistant depression as shown by lack of response of the current depressive episode to 2 or more adequate courses of antidepressant therapy at a clinically appropriate dose for at least 4 weeks or, in the judgment of the investigator, the participant has treatment-resistant depression

• Have a lifetime history of vagal nerve stimulation (VNS), transcranial magnetic stimulation (TMS), or psychosurgery

• Have received electroconvulsive therapy (ECT) in the past year

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Garden Grove	California	United States	92845
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oakland	California	United States	94612
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Temecula	California	United States	92591
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Waterbury	Connecticut	United States	06708
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boca Raton	Florida	United States	33432
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Myers	Florida	United States	33912
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	North Bay Village	Florida	United States	33141
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oakland Park	Florida	United States	33334
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orlando	Florida	United States	32839
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	West Palm Beach	Florida	United States	33407
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shreveport	Louisiana	United States	71101
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lincoln	Nebraska	United States	68526
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Marlton	New Jersey	United States	08053
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Brooklyn	New York	United States	11241
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York	United States	10003
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Staten Island	New York	United States	10312
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cincinnati	Ohio	United States	45215
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Media	Pennsylvania	United States	19063
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Herndon	Virginia	United States	20170
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Richmond	Virginia	United States	23230
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Everton Park	Queensland	Australia	4053
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Spring Hill	Queensland	Australia	4000
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Frankston	Victoria	Australia	3199
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Heidelberg	Victoria	Australia	3084
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Malvern	Victoria	Australia	3144
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Melbourne	Victoria	Australia	3004
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vienna		Austria	A1090
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Diest		Belgium	3290
29	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Liège		Belgium	4000
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mont-Godinne		Belgium	5530
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bad Saarow		Germany	15526
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	12209
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bochum		Germany	44892
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cham		Germany	93413
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dresden		Germany	01097
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hattingen		Germany	45525
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leipzig		Germany	04107
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Munich		Germany	80331
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nürnberg		Germany	90402
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Prien		Germany	83209
41	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Schwerin		Germany	19053
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Goteborg		Sweden	41685
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lund		Sweden	222 22
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Malmo		Sweden	21153
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Solna		Sweden	171 45
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stockholm		Sweden	11486
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bexhill-On-Sea	East Sussex	United Kingdom	TN40 1JJ
48	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Glasgow	Scotland	United Kingdom	G20 0XA
49	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chesterfield		United Kingdom	S40 4TF

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01185340
• Other Study ID Numbers: 12183; H9P-MC-LNBR
• First Posted: Aug 19, 2010
• Last Update Posted: Apr 27, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Eli Lilly and Company: Depression; MDD
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Serotonin; Serotonin Uptake Inhibitors

Study Results

Participant Flow

Pre-assignment Detail	The first 3 weeks of the study was a double-blind Confirmation Phase during which participants continued to receive their SSRI with adjunctive placebo. If randomization criteria were met, participants were randomized to adjunctive LY2216684 or adjunctive placebo. If criteria were not met, participants continued on placebo to maintain the blind.

Arm/Group Title	Placebo + SSRI (Pre-randomized Participants)	LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)	Placebo + SSRI (Non-randomized Participants)
Arm/Group Description	Placebo: Administered orally, once daily for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Period Title: Confirmation (CF) Phase, 3 Weeks
STARTED	1056	0	0	0
Entered Discontinuation (DC) Phase	18	0	0	0
COMPLETED	968	0	0	0
NOT COMPLETED	88	0	0	0
Period Title: Confirmation (CF) Phase, 3 Weeks
STARTED	0	230	219	519
Entered Discontinuation (DC) Phase	0	206	204	483
COMPLETED	0	195	186	458
NOT COMPLETED	0	35	33	61

Baseline Characteristics

Arm/Group Title	LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)	Placebo + SSRI (Non-randomized Participants)	Total
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Total of all reporting groups
Overall Participants	230	219	519	968
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.29 (11.90)	48.44 (11.39)	47.39 (12.68)	47.84 (12.21)
Sex: Female, Male (Count of Participants)
Female	155 67.4%	145 66.2%	354 68.2%	654 67.6%
Male	75 32.6%	74 33.8%	165 31.8%	314 32.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 8.3%	12 5.5%	31 6%	62 6.4%
Not Hispanic or Latino	164 71.3%	158 72.1%	370 71.3%	692 71.5%
Unknown or Not Reported	47 20.4%	49 22.4%	118 22.7%	214 22.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	3 0.6%	3 0.3%
Asian	2 0.9%	1 0.5%	3 0.6%	6 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	17 7.4%	31 14.2%	53 10.2%	101 10.4%
White	207 90%	185 84.5%	457 88.1%	849 87.7%
More than one race	4 1.7%	2 0.9%	2 0.4%	8 0.8%
Unknown or Not Reported	0 0%	0 0%	1 0.2%	1 0.1%
Region of Enrollment (Count of Participants)
United States	93 40.4%	89 40.6%	195 37.6%	377 38.9%
Belgium	7 3%	4 1.8%	13 2.5%	24 2.5%
Austria	10 4.3%	10 4.6%	25 4.8%	45 4.6%
Australia	22 9.6%	20 9.1%	84 16.2%	126 13%
Germany	58 25.2%	63 28.8%	95 18.3%	216 22.3%
United Kingdom	19 8.3%	15 6.8%	30 5.8%	64 6.6%
Sweden	21 9.1%	18 8.2%	77 14.8%	116 12%

Outcome Measures

1. Primary Outcome

Title	Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description	The Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	225	217
Least Squares Mean (Standard Error) [units on a scale]	-8.73 (0.55)	-8.49 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2216684 + SSRI, Placebo + SSRI
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.751
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Score
Description	The Sheehan Disability Scale (SDS) was completed by the participant and used to assess the effect of the participant's symptoms on their work (Item 1), social (Item 2), and family life (Item 3). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. The Global Functional Impairment Score is the sum of the 3 items, and scores ranged from 0 to 30 with higher values indicating greater disruption in the participant's work life (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	218	208
Least Squares Mean (Standard Error) [units on a scale]	-4.50 (0.47)	-4.38 (0.48)

3. Secondary Outcome

Title	Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Impact Subscale Score
Description	The Fatigue Associated with Depression (FAsD) is a participant-rated scale with a total of 13 items. Six of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Seven of the 13 items ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The impact subscale score was derived by taking the mean of Items 7 through 13 (applicable items only). Item 12 applied only to participants with a spouse or significant other, and Item 13 applied to participants who had a job or who went to school. The FAsD impact subscale score ranges from 1 to 5. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	218	209
Least Squares Mean (Standard Error) [units on a scale]	-0.69 (0.06)	-0.59 (0.07)

4. Secondary Outcome

Title	Probability of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 at Week 8
Description	A Montgomery-Asberg Depression Rating Scale (MADRS) total score of less than or equal to 10 was defined as remission criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). A categorical repeated measures analysis modeled the probability of remission at each visit, and the estimated probabilities were adjusted for treatment, visit, baseline MADRS total score, and treatment-by-visit.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	225	217
Least Squares Mean (Standard Error) [probability]	0.313 (0.034)	0.251 (0.032)

5. Secondary Outcome

Title	Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement
Description	A Montgomery-Asberg Depression Rating Scale (MADRS) total score of less than or equal to 10 for at least 2 consecutive measurements, including the participant's last measurement was defined as remission criteria at last 2 consecutive visits. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Percentage of participants was calculated by dividing the number of participants who meet criteria for remission at last 2 consecutive visits by the total number of participants analyzed, multiplied by 100%.
Time Frame	Randomization up to 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	225	218
Number [percentage of participants]	20.89 9.1%	17.89 8.2%

6. Secondary Outcome

Title	Change From Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score
Description	The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression subscale. Scores of 11 or more on either subscale were considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	224	217
Least Squares Mean (Standard Error) [units on a scale]	-2.20 (0.22)	-1.78 (0.23)

7. Secondary Outcome

Title	Probability of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8
Description	A greater than or equal to 50 percent improvement (that is, a decrease from baseline) in the Montgomery-Asberg Depression Rating Scale (MADRS) total score was defined as response criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). A categorical repeated measures analysis modeled the probability of response at each visit, and the estimated probabilities were adjusted for treatment, visit, baseline MADRS total score, and treatment-by-visit.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	225	217
Least Squares Mean (Standard Error) [probability]	0.357 (0.034)	0.352 (0.034)

8. Secondary Outcome

Title	Change From Randomization to Week 8 in The Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score
Description	The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression subscale. Scores of 11 or more on either subscale were considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	224	217
Least Squares Mean (Standard Error) [units on a scale]	-2.82 (0.27)	-2.64 (0.27)

9. Secondary Outcome

Title	Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Description	The Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline item score, treatment-by-visit and baseline item score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	225	217
Apparent Sadness	-1.10 (0.09)	-1.26 (0.09)
Reported Sadness	-1.17 (0.09)	-1.19 (0.09)
Inner Tension	-0.72 (0.08)	-0.71 (0.09)
Reduced Sleep	-0.83 (0.09)	-0.76 (0.10)
Reduced Appetite	-0.54 (0.08)	-0.72 (0.08)
Concentration Difficulties	-1.07 (0.09)	-0.82 (0.09)
Lassitude	-1.11 (0.09)	-0.98 (0.09)
Inability to Feel	-1.17 (0.09)	-1.08 (0.09)
Pessimistic Thoughts	-0.88 (0.08)	-0.77 (0.08)
Suicidal Thoughts	-0.23 (0.05)	-0.24 (0.05)

10. Secondary Outcome

Title	Change From Randomization to Week 8 in Clinical Global Impressions of Severity (CGI-S)
Description	Clinical Global Impression - Severity (CGI-S) measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	224	217
Least Squares Mean (Standard Error) [units on a scale]	-1.08 (0.08)	-1.02 (0.08)

11. Secondary Outcome

Title	Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score
Description	The Fatigue Associated with Depression (FAsD) is a participant-rated scale with a total of 13 items. Six of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Seven of the 13 items ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score was derived by taking the mean of Items 1 through 6, and the average score was the mean of Items 1 through 13 (derived by taking the mean of all applicable items for each participant). Item 12 applied only to participants with a spouse or significant other, and Item 13 applied to participants who had a job or who went to school. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	217	210
FAsD average score	-0.62 (0.06)	-0.55 (0.06)
FAsD experience subscale score	-0.57 (0.06)	-0.50 (0.06)

12. Secondary Outcome

Title	Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items
Description	The Sheehan Disability Scale (SDS) was completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline item score, treatment-by-visit, and baseline item score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	218	209
Work impairment score	-1.41 (0.22)	-1.20 (0.22)
Social life impairment score	-1.64 (0.17)	-1.53 (0.17)
Family life impairment score	-1.56 (0.17)	-1.53 (0.17)

13. Secondary Outcome

Title	Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)
Description	The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) is a self-administered, 16-item questionnaire measuring degree of enjoyment and satisfaction experienced in various areas of daily life during the past week on a 5-point Likert scale (1=very poor and 5=very good). The total raw score is the sum of Items 1 to 14 and ranges from 14 to 70. The raw scores are converted to and expressed as the percentage of the maximum possible score. Higher scores indicate higher levels of enjoyment/satisfaction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	218	208
Least Squares Mean (Standard Error) [percentage of the maximum possible score]	10.37 (1.09)	9.30 (1.12)

14. Secondary Outcome

Title	Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)
Description	The EQ-5D Visual Analog Scale is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score is self-reported using a visual analogue scale, marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	216	209
Least Squares Mean (Standard Error) [units on a scale]	10.367 (1.218)	9.644 (1.252)

15. Secondary Outcome

Title	Percentage of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	The Columbia-Suicide Severity Rating Scale (C-SSRS) captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation was defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which included a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present at baseline. Percentage of participants was calculated by dividing the number of participants with suicide-related TE events by the total number of participants at risk, multiplied by 100%. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time Frame	Randomization up to 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	224	218
TE suicidal ideation	4.46 1.9%	5.96 2.7%
TE suicidal behavior	0.00 0%	0.52 0.2%

16. Secondary Outcome

Title	Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale
Description	The Arizona Sexual Experiences (ASEX) scale was used to assess sexual functioning in both males and females. The ASEX total score for the male and female version was calculated as the sum of the responses (rated from 1 [extremely] to 6 [no/never]) of the 5 items of the ASEX scale. Total scores ranged from 5 to 30, with higher scores indicating greater sexual dysfunction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	214	204
Least Squares Mean (Standard Error) [units on a scale]	-0.92 (0.25)	-0.68 (0.26)

17. Secondary Outcome

Title	Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
Description	The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item was scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total scores ranged from 7 to 42. Higher scores indicate greater disease severity. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	218	210
Least Squares Mean (Standard Error) [units on a scale]	-4.12 (0.39)	-3.68 (0.40)

18. Secondary Outcome

Title	Change From Randomization to Week 8 in Blood Pressure
Description	Blood pressure measurements were collected when the participant was in a sitting position. Three measurements of sitting blood pressure collected at approximately 1-minute intervals at every visit were averaged and used as the value for the visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	225	217
Systolic blood pressure	3.09 (0.67)	0.27 (0.69)
Diastolic blood pressure	4.54 (0.53)	0.53 (0.54)

19. Secondary Outcome

Title	Change From Randomization to Week 8 in Pulse Rate
Description	Pulse measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.
Time Frame	Randomization, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Measure Participants	225	216
Least Squares Mean (Standard Error) [beats per minute (bpm)]	9.64 (0.67)	-1.49 (0.69)

Adverse Events

Time Frame	Confirmation (CF) Phase: Week 0 through Week 3 Adjunctive Treatment (AT) Phase: Week 4 through Week 11 Discontinuation (DC) Phase: The week following completion of the AT Phase (Week 12) or early discontinuation of the CF Phase or AT Phase
Arm/Group Title	Placebo + SSRI (Pre-randomized) - CF Phase		LY2216684 + SSRI (Randomized) - AT Phase		Placebo + SSRI (Randomized) - AT Phase		Placebo + SSRI (Non-randomized) - AT Phase		Placebo + SSRI (Pre-randomized) - DC Phase		LY2216684 + SSRI (Randomized) - DC Phase		Placebo + SSRI (Randomized) - DC Phase		Placebo + SSRI (Non-randomized) - DC Phase
Arm/Group Description	Placebo: Administered orally, once daily for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes all enrolled participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Confirmation (CF) Phase.		LY2216684: 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.		Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.		Placebo: Administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes all non-randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.		No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week. Includes all enrolled participants who abruptly discontinued placebo after early withdrawal during the Confirmation (CF) Phase and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.		No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week. Includes all randomized participants who abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.		No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week. Includes all randomized participants who abruptly discontinued placebo either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.		No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week. Includes all non-randomized participants who abruptly discontinued placebo either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
All Cause Mortality
	Placebo + SSRI (Pre-randomized) - CF Phase		LY2216684 + SSRI (Randomized) - AT Phase		Placebo + SSRI (Randomized) - AT Phase		Placebo + SSRI (Non-randomized) - AT Phase		Placebo + SSRI (Pre-randomized) - DC Phase		LY2216684 + SSRI (Randomized) - DC Phase		Placebo + SSRI (Randomized) - DC Phase		Placebo + SSRI (Non-randomized) - DC Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + SSRI (Pre-randomized) - CF Phase		LY2216684 + SSRI (Randomized) - AT Phase		Placebo + SSRI (Randomized) - AT Phase		Placebo + SSRI (Non-randomized) - AT Phase		Placebo + SSRI (Pre-randomized) - DC Phase		LY2216684 + SSRI (Randomized) - DC Phase		Placebo + SSRI (Randomized) - DC Phase		Placebo + SSRI (Non-randomized) - DC Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/1052 (0.9%)		7/228 (3.1%)		7/218 (3.2%)		12/519 (2.3%)		1/18 (5.6%)		2/206 (1%)		4/202 (2%)		4/482 (0.8%)
Cardiac disorders
Atrial fibrillation	0/1052 (0%)	0	0/228 (0%)	0	2/218 (0.9%)	2	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	1/202 (0.5%)	1	0/482 (0%)	0
Myocardial infarction	0/1052 (0%)	0	1/228 (0.4%)	1	0/218 (0%)	0	0/519 (0%)	0	0/18 (0%)	0	1/206 (0.5%)	1	0/202 (0%)	0	0/482 (0%)	0
Gastrointestinal disorders
Faecaloma	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Food poisoning	0/1052 (0%)	0	1/228 (0.4%)	1	0/218 (0%)	0	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Gastritis	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	1/482 (0.2%)	1
General disorders
Non-cardiac chest pain	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Infections and infestations
Pneumonia	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	1/482 (0.2%)	1
Postoperative wound infection	1/1052 (0.1%)	1	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Injury, poisoning and procedural complications
Facial bones fracture	1/1052 (0.1%)	1	0/228 (0%)	0	0/218 (0%)	0	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Multiple injuries	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Road traffic accident	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Tibia fracture	1/1052 (0.1%)	1	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Investigations
Blood creatinine increased	0/1052 (0%)	0	1/228 (0.4%)	1	1/218 (0.5%)	1	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Blood urea increased	0/1052 (0%)	0	1/228 (0.4%)	1	0/218 (0%)	0	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus	1/1052 (0.1%)	1	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome	1/1052 (0.1%)	1	0/228 (0%)	0	1/218 (0.5%)	1	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	1/202 (0.5%)	1	0/482 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/1052 (0%)	0	1/228 (0.4%)	1	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Nervous system disorders
Cerebral infarction	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Sciatica	1/1052 (0.1%)	1	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	1/482 (0.2%)	1
Psychiatric disorders
Anxiety	1/1052 (0.1%)	1	0/228 (0%)	0	0/218 (0%)	0	0/519 (0%)	0	1/18 (5.6%)	1	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Depression	1/1052 (0.1%)	1	2/228 (0.9%)	2	0/218 (0%)	0	0/519 (0%)	0	0/18 (0%)	0	1/206 (0.5%)	1	0/202 (0%)	0	0/482 (0%)	0
Major depression	0/1052 (0%)	0	1/228 (0.4%)	1	0/218 (0%)	0	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Suicidal ideation	0/1052 (0%)	0	0/228 (0%)	0	2/218 (0.9%)	2	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	2/202 (1%)	2	0/482 (0%)	0
Suicide attempt	1/1052 (0.1%)	1	0/228 (0%)	0	2/218 (0.9%)	2	0/519 (0%)	0	0/18 (0%)	0	0/206 (0%)	0	1/202 (0.5%)	1	0/482 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	1/482 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/1052 (0%)	0	0/228 (0%)	0	0/218 (0%)	0	1/519 (0.2%)	1	0/18 (0%)	0	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo + SSRI (Pre-randomized) - CF Phase		LY2216684 + SSRI (Randomized) - AT Phase		Placebo + SSRI (Randomized) - AT Phase		Placebo + SSRI (Non-randomized) - AT Phase		Placebo + SSRI (Pre-randomized) - DC Phase		LY2216684 + SSRI (Randomized) - DC Phase		Placebo + SSRI (Randomized) - DC Phase		Placebo + SSRI (Non-randomized) - DC Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	270/1052 (25.7%)		87/228 (38.2%)		44/218 (20.2%)		128/519 (24.7%)		5/18 (27.8%)		39/206 (18.9%)		22/202 (10.9%)		70/482 (14.5%)
Gastrointestinal disorders
Abdominal discomfort	6/1052 (0.6%)	7	2/228 (0.9%)	2	0/218 (0%)	0	2/519 (0.4%)	2	1/18 (5.6%)	1	1/206 (0.5%)	1	0/202 (0%)	0	2/482 (0.4%)	2
Dry mouth	33/1052 (3.1%)	35	9/228 (3.9%)	9	4/218 (1.8%)	4	7/519 (1.3%)	7	1/18 (5.6%)	1	2/206 (1%)	2	0/202 (0%)	0	1/482 (0.2%)	1
Nausea	54/1052 (5.1%)	56	19/228 (8.3%)	24	7/218 (3.2%)	9	16/519 (3.1%)	17	2/18 (11.1%)	2	4/206 (1.9%)	4	5/202 (2.5%)	5	10/482 (2.1%)	10
Vomiting	7/1052 (0.7%)	7	14/228 (6.1%)	16	4/218 (1.8%)	5	7/519 (1.3%)	7	1/18 (5.6%)	1	2/206 (1%)	2	1/202 (0.5%)	1	1/482 (0.2%)	1
Infections and infestations
Nasopharyngitis	36/1052 (3.4%)	37	12/228 (5.3%)	13	11/218 (5%)	12	31/519 (6%)	31	1/18 (5.6%)	1	2/206 (1%)	2	0/202 (0%)	0	6/482 (1.2%)	6
Nervous system disorders
Dizziness	28/1052 (2.7%)	30	14/228 (6.1%)	14	6/218 (2.8%)	6	7/519 (1.3%)	7	1/18 (5.6%)	1	3/206 (1.5%)	3	4/202 (2%)	4	9/482 (1.9%)	9
Headache	117/1052 (11.1%)	137	26/228 (11.4%)	35	14/218 (6.4%)	17	53/519 (10.2%)	64	3/18 (16.7%)	3	27/206 (13.1%)	30	14/202 (6.9%)	14	47/482 (9.8%)	53
Somnolence	11/1052 (1%)	12	0/228 (0%)	0	1/218 (0.5%)	1	3/519 (0.6%)	3	1/18 (5.6%)	1	0/206 (0%)	0	0/202 (0%)	0	2/482 (0.4%)	2
Tension headache	2/1052 (0.2%)	2	1/228 (0.4%)	1	1/218 (0.5%)	1	3/519 (0.6%)	3	1/18 (5.6%)	1	0/206 (0%)	0	0/202 (0%)	0	0/482 (0%)	0
Tremor	4/1052 (0.4%)	4	4/228 (1.8%)	5	0/218 (0%)	0	4/519 (0.8%)	4	1/18 (5.6%)	1	2/206 (1%)	2	1/202 (0.5%)	1	4/482 (0.8%)	4
Psychiatric disorders
Disorientation	0/1052 (0%)	0	1/228 (0.4%)	1	0/218 (0%)	0	0/519 (0%)	0	1/18 (5.6%)	1	0/206 (0%)	0	0/202 (0%)	0	1/482 (0.2%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	29/1052 (2.8%)	29	27/228 (11.8%)	27	2/218 (0.9%)	2	14/519 (2.7%)	14	0/18 (0%)	0	4/206 (1.9%)	4	1/202 (0.5%)	1	1/482 (0.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.