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Trial record 10 of 1269 for:    depression AND Major Depression AND depressive symptoms | "Depression"

A Study in Prevention of Re-emergence of Depression Symptoms

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ClinicalTrials.gov Identifier: NCT01299272
Recruitment Status : Completed
First Posted : February 18, 2011
Results First Posted : April 17, 2018
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: LY2216684
Drug: Placebo
Drug: SSRI
Enrollment 1249

Recruitment Details  
Pre-assignment Details All enrolled participants entered the Acute Open-label (OL) Period. At Week 8, if remission criteria were met, participants entered the Stabilization OL Period. At Week 20, if randomization criteria were met, participants entered the 24-week Double-blind Randomized Withdrawal Period. Those who discontinued early entered the Discontinuation Period.
Arm/Group Title LY2216684 + SSRI (Acute Open-label Period) LY2216684 + SSRI (Stabilization Open-label Period) LY2216684 + SSRI (Double-blind Randomized Withdrawal Period) Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Hide Arm/Group Description Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for an additional 12 weeks. Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks. Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Period Title: Acute Open-label (OL) Period
Started 1249 0 0 0
Entered Discontinuation (DC) Period 271 [1] 0 0 0
Completed 835 [2] 0 0 0
Not Completed 414 0 0 0
Reason Not Completed
Remission Criteria Not Met             140             0             0             0
Adverse Event             140             0             0             0
Withdrawal by Subject             56             0             0             0
Protocol Violation             36             0             0             0
Lost to Follow-up             14             0             0             0
Sponsor Decision             13             0             0             0
Lack of Efficacy             10             0             0             0
Physician Decision             5             0             0             0
[1]
Participants who discontinued the Acute OL Period had the option to enter the DC Period.
[2]
Participants who completed the Acute OL Period entered the Stabilization OL Period.
Period Title: Stabilization Open-label (OL) Period
Started 0 835 0 0
Entered Discontinuation (DC) Period 0 164 [1] 0 0
Completed 0 586 [2] 0 0
Not Completed 0 249 0 0
Reason Not Completed
Randomization Criteria Not Met             0             80             0             0
Protocol Violation             0             44             0             0
Adverse Event             0             42             0             0
Withdrawal by Subject             0             42             0             0
Sponsor Decision             0             12             0             0
Lack of Efficacy             0             11             0             0
Lost to Follow-up             0             9             0             0
Reemergence of Study Condition Symptoms             0             6             0             0
Physician Decision             0             3             0             0
[1]
Participants who discontinued the Stabilization OL Period had the option to enter the DC Period.
[2]
Participants who completed the Stabilization OL Period were randomized to the DB Period.
Period Title: Double-blind (DB) Randomized Period
Started 0 0 294 292
Entered Taper Discontinuation Period 0 0 129 [1] 0
Entered Abrupt Discontinuation Period 0 0 132 [2] 268 [3]
Completed 0 0 224 234
Not Completed 0 0 70 58
Reason Not Completed
Withdrawal by Subject             0             0             22             15
Lack of Efficacy             0             0             20             10
Adverse Event             0             0             8             9
Protocol Violation             0             0             8             7
Lost to Follow-up             0             0             5             5
Reemergence of Study Condition Symptoms             0             0             4             10
Physician Decision             0             0             2             1
Sponsor Decision             0             0             1             1
[1]
Participants who completed or discontinued the DB Period were randomized to the taper DC Period.
[2]
Participants who completed or discontinued the DB Period were randomized to the abrupt DC Period.
[3]
Participants who completed or discontinued the DB Period entered the DC Period.
Arm/Group Title All Enrolled Participants
Hide Arm/Group Description All enrolled participants started on a flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for an additional 12 weeks. At 20 weeks, participants meeting criteria for randomization either 1) continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks or 2) were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Baseline Participants 1249
Hide Baseline Analysis Population Description
All enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1249 participants
47.4  (12.54)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1249 participants
Female 917
Male 332
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1249 participants
American Indian or Alaska Native 50
Asian 21
Native Hawaiian or Other Pacific Islander 0
Black or African American 99
White 1066
More than one race 13
Unknown or Not Reported 0
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1249 participants
Hispanic or Latino 254
Not Hispanic or Latino 622
Unknown or Not Reported 373
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1249 participants
United States 535
Slovakia 65
Greece 43
Spain 43
Turkey 30
Russia 96
Italy 44
France 61
Mexico 63
Puerto Rico 77
Argentina 62
Belgium 11
Croatia 9
Romania 19
Germany 73
South Korea 18
1.Primary Outcome
Title Percentage of Participants Who Meet Criteria for Re-emergence of Depressive Symptoms Estimated by Kaplan-Meier Product Limit Method (Double-blind Randomized Withdrawal Period)
Hide Description Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. Time from randomization to the first visit at which the participant met the reemergence criteria was calculated. The percentage of participants who meet criteria was estimated using the Kaplan-Meier product limit method. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high 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 (extremely ill).
Time Frame Randomization up to 44 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 294 292
Measure Type: Number
Unit of Measure: percentage of participants
10.43 8.24
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2216684 + SSRI, Placebo + SSRI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.485
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Re-emergence of Depressive Symptoms (Double-blind Randomized Withdrawal Period)
Hide Description Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. The percentage of participants with re-emergence of depressive symptoms was calculated by dividing the number of participants who meet any of the criteria by the total number of participants analyzed, multiplied by 100. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high 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 (extremely ill).
Time Frame Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 294 292
Measure Type: Number
Unit of Measure: percentage of participants
9.9 8.2
3.Secondary Outcome
Title Change From Randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, 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 a mixed model repeated measures (MMRM) analysis which includes terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline MADRS total score (individual item score) and baseline MADRS total score (individual item score)-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 290 292
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
MADRS Total Score 0.40  (0.33) 0.34  (0.33)
Item 1: Apparent Sadness 0.09  (0.05) 0.08  (0.05)
Item 2: Reported Sadness 0.09  (0.06) 0.05  (0.06)
Item 3: Inner Tension 0.06  (0.07) 0.14  (0.06)
Item 4: Reduced Sleep -0.02  (0.07) -0.06  (0.07)
Item 5: Reduced Appetite 0.00  (0.04) -0.00  (0.04)
Item 6: Concentration Difficulties 0.07  (0.06) 0.08  (0.06)
Item 7: Lassitude 0.02  (0.06) 0.07  (0.06)
Item 8: Inability to Feel -0.00  (0.05) -0.05  (0.05)
Item 9: Pessimistic Thoughts -0.01  (0.05) -0.02  (0.04)
Item 10: Suicidal Thoughts 0.02  (0.02) 0.01  (0.02)
4.Secondary Outcome
Title Change From Randomization in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are 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 a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline subscale score and baseline subscale score-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 286 285
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
HADS Anxiety Subscale Score -0.00  (0.22) 0.15  (0.22)
HADS Depression Subscale Score -0.18  (0.23) 0.15  (0.23)
5.Secondary Outcome
Title Change From Randomization in the Clinical Global Impression of Severity (CGI-S) Scores at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CGI-S score and baseline CGI-S score-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 290 292
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.01  (0.05) -0.00  (0.05)
6.Secondary Outcome
Title Change From Randomization in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description The FAsD is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 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 is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 286 286
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
FAsD Experience Subscale Score -0.05  (0.05) 0.05  (0.05)
FAsD Impact Subscale Score -0.06  (0.05) -0.01  (0.05)
FAsD Average Score -0.05  (0.05) 0.02  (0.05)
7.Secondary Outcome
Title Change From Randomization in the Sheehan Disability Scale (SDS) Items at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description The Sheehan Disability Scale (SDS) is 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 a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 289 289
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Work Impairment Score Number Analyzed 198 participants 212 participants
-0.24  (0.17) 0.02  (0.17)
Social Life Impairment Score Number Analyzed 286 participants 286 participants
-0.17  (0.14) -0.15  (0.14)
Family Life Impairment Score Number Analyzed 286 participants 286 participants
-0.26  (0.14) -0.08  (0.14)
8.Secondary Outcome
Title Change From Randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) model with main effects of treatment, country, and baseline score.
Time Frame Randomization, up to Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 278 285
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
EQ-5D US Number Analyzed 278 participants 284 participants
0.01  (0.01) 0.01  (0.01)
EQ-5D UK Number Analyzed 278 participants 284 participants
0.01  (0.02) 0.01  (0.02)
VAS Number Analyzed 278 participants 285 participants
1.87  (1.39) 0.61  (1.39)
9.Secondary Outcome
Title Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Double-blind Randomized Withdrawal Period)
Hide Description The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is 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 during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time Frame Randomization through Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 291 292
Measure Type: Number
Unit of Measure: participants
TE Suicidal Ideation Number Analyzed 291 participants 292 participants
5 4
TE Suicidal Behavior Number Analyzed 277 participants 278 participants
1 0
10.Secondary Outcome
Title Change From Randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline ASEX total score and baseline ASEX total score-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 280 277
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.39  (0.33) -0.08  (0.33)
11.Secondary Outcome
Title Change From Randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description 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 is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CPFQ total score and baseline CPFQ total score-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 286 286
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.27  (0.31) -0.05  (0.31)
12.Secondary Outcome
Title Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 8 (Acute Open-label Period)
Hide Description Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame Baseline, up to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Overall Number of Participants Analyzed 1214
Mean (Standard Deviation)
Unit of Measure: units on a scale
MADRS Total Score -13.21  (8.30)
Item 1: Apparent Sadness -1.82  (1.37)
Item 2: Reported Sadness -1.86  (1.39)
Item 3: Inner Tension -1.24  (1.37)
Item 4: Reduced Sleep -1.29  (1.57)
Item 5: Reduced Appetite -0.65  (1.47)
Item 6: Concentration Difficulties -1.49  (1.43)
Item 7: Lassitude -1.74  (1.44)
Item 8: Inability to Feel -1.65  (1.42)
Item 9: Pessimistic Thoughts -1.23  (1.28)
Item 10: Suicidal Thoughts -0.24  (0.70)
13.Secondary Outcome
Title Change From Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 20 (Stabilization Open-label Period)
Hide Description Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame Week 8, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 812
Mean (Standard Deviation)
Unit of Measure: units on a scale
MADRS Total Score -0.38  (6.09)
Item 1: Apparent Sadness -0.01  (1.01)
Item 2: Reported Sadness -0.08  (1.15)
Item 3: Inner Tension -0.05  (1.18)
Item 4: Reduced Sleep -0.12  (1.28)
Item 5: Reduced Appetite 0.00  (0.89)
Item 6: Concentration Difficulties -0.06  (1.19)
Item 7: Lassitude 0.02  (1.19)
Item 8: Inability to Feel -0.09  (1.08)
Item 9: Pessimistic Thoughts -0.04  (0.87)
Item 10: Suicidal Thoughts 0.03  (0.47)
14.Secondary Outcome
Title Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 8 (Acute Open-label Period)
Hide Description The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. 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'.
Time Frame Baseline, up to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Overall Number of Participants Analyzed 1199
Mean (Standard Deviation)
Unit of Measure: units on a scale
HADS Anxiety Subscale Score Number Analyzed 1198 participants
-3.02  (3.92)
HADS Depression Subscale Score Number Analyzed 1199 participants
-3.98  (4.41)
15.Secondary Outcome
Title Change From Week 8 in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 20 (Stabilization Open-label Period)
Hide Description The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'.
Time Frame Week 8, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 781
Mean (Standard Deviation)
Unit of Measure: units on a scale
HADS Anxiety Subscale Score -0.77  (3.73)
HADS Depression Subscale Score -0.74  (3.57)
16.Secondary Outcome
Title Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 8 (Acute Open-label Period)
Hide Description The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame Baseline, up to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Overall Number of Participants Analyzed 1214
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.51  (1.17)
17.Secondary Outcome
Title Change From Week 8 in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 20 (Stabilization Open-label Period)
Hide Description The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame Week 8, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 812
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.25  (0.95)
18.Secondary Outcome
Title Change From Baseline in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 8 (Acute Open-label Period)
Hide Description The Fatigue Associated With Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 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 is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.
Time Frame Baseline, up to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Overall Number of Participants Analyzed 1166
Mean (Standard Deviation)
Unit of Measure: units on a scale
FAsD Experience Subscale Score Number Analyzed 1166 participants
-0.82  (0.99)
FAsD Impact Subscale Score Number Analyzed 1164 participants
-0.88  (1.03)
FAsD Average Score Number Analyzed 1164 participants
-0.85  (0.93)
19.Secondary Outcome
Title Change From Week 8 in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 20 (Stabilization Open-label Period)
Hide Description The Fatigue Associated with Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 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 is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.
Time Frame Week 8, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 781
Mean (Standard Deviation)
Unit of Measure: units on a scale
FAsD Experience Subscale Score -0.22  (0.93)
FAsD Impact Subscale Score -0.15  (0.87)
FAsD Average Score -0.19  (0.84)
20.Secondary Outcome
Title Change From Baseline in the Sheehan Disability Scale (SDS) Items up to Week 8 (Acute Open-label Period)
Hide Description The Sheehan Disability Scale (SDS) is 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.
Time Frame Baseline, up to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Overall Number of Participants Analyzed 1197
Mean (Standard Deviation)
Unit of Measure: units on a scale
Work Impairment Score Number Analyzed 757 participants
-2.17  (2.65)
Social Life Impairment Score Number Analyzed 1197 participants
-2.38  (2.85)
Family Life Impairment Score Number Analyzed 1197 participants
-2.16  (2.81)
21.Secondary Outcome
Title Change From Week 8 in the Sheehan Disability Scale (SDS) Items up to Week 20 (Stabilization Open-label Period)
Hide Description The Sheehan Disability Scale (SDS) is 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.
Time Frame Week 8, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 781
Mean (Standard Deviation)
Unit of Measure: units on a scale
Work Impairment Score Number Analyzed 567 participants
-0.58  (2.61)
Social Life Impairment Score Number Analyzed 781 participants
-0.47  (2.54)
Family Life Impairment Score Number Analyzed 781 participants
-0.50  (2.50)
22.Secondary Outcome
Title Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 20 (Open-label Period)
Hide Description The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health).
Time Frame Baseline, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 779
Mean (Standard Deviation)
Unit of Measure: units on a scale
EQ-5D US Number Analyzed 773 participants
0.15  (0.19)
EQ-5D UK Number Analyzed 773 participants
0.21  (0.29)
VAS Number Analyzed 779 participants
18.07  (22.15)
23.Secondary Outcome
Title Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Open-label Period)
Hide Description The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is 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 is 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. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time Frame Baseline through Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 1216
Measure Type: Number
Unit of Measure: participants
TE Suicidal Ideation Number Analyzed 1216 participants
66
TE Suicidal Behavior Number Analyzed 1124 participants
5
24.Secondary Outcome
Title Change From Baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (Open-label Period)
Hide Description Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction.
Time Frame Baseline, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 1115
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.78  (4.98)
25.Secondary Outcome
Title Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 20 (Open-label Period)
Hide Description 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 is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment.
Time Frame Baseline, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 1167
Mean (Standard Deviation)
Unit of Measure: units on a scale
-6.68  (7.03)
26.Secondary Outcome
Title Change From Randomization in Blood Pressure at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 291 292
Least Squares Mean (Standard Error)
Unit of Measure: millimeters of mercury (mmHg)
Systolic blood pressure -0.20  (0.75) -4.19  (0.75)
Diastolic blood pressure 0.24  (0.55) -4.18  (0.55)
27.Secondary Outcome
Title Change From Baseline in Blood Pressure up to Week 20 (Open-label Period)
Hide Description Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis.
Time Frame Baseline, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 1214
Mean (Standard Deviation)
Unit of Measure: millimeters of mercury (mmHg)
Systolic blood pressure 2.30  (11.95)
Diastolic blood pressure 2.81  (8.63)
28.Secondary Outcome
Title Change From Randomization in Pulse Rate at Week 44 (Double-blind Randomized Withdrawal Period)
Hide Description Pulse rate measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.
Time Frame Randomization, Week 44
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Number of Participants Analyzed 291 292
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
-2.54  (0.74) -10.76  (0.74)
29.Secondary Outcome
Title Change From Baseline in Pulse Rate up to Week 20 (Open-label Period)
Hide Description Pulse measurements were collected when the participant was in a sitting position.
Time Frame Baseline, up to Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Overall Number of Participants Analyzed 1214
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
10.80  (12.47)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LY2216684 + SSRI (Acute Open-label Period) LY2216684 + SSRI (Stabilization Open-label Period) LY2216684 + SSRI (Double-blind Randomized Withdrawal Period) Placebo + SSRI (Double-blind Randomized Withdrawal Period) LY2216684 + SSRI (Randomized Tapered Discontinuation Period) LY2216684 + SSRI (Randomized Abrupt Discontinuation Period) Placebo + SSRI (Abrupt Discontinuation Period) LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
Hide Arm/Group Description

Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 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 Acute Open-label Period.

Same, stable dose of LY2216684 as in the Acute Open-label Period, orally, once daily (QD) for 12 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).

Includes all participants who completed the Acute Open-label Period and did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Stabilization Open-label Period.

Same, stable dose of LY2216684 as in the Stabilization Open-label Period, orally, once daily (QD) for 24 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 Double-blind Randomized Withdrawal Period.

Placebo, orally, once daily (QD) for 24 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 Double-blind Randomized Withdrawal Period.

12 milligrams (mg) LY2216684 for 4 days, 6 mg LY2216684 for 4 days, then placebo for 6 days, orally, once daily (QD), adjunctive to a selective serotonin reuptake inhibitor (SSRI).

Includes all randomized participants who tapered discontinuation of LY2216684 after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).

Includes all randomized participants who abruptly discontinued LY2216684 after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).

Includes all randomized participants who discontinued placebo after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).

Includes all non-randomized participants who discontinued early from either Open-label Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

All-Cause Mortality
LY2216684 + SSRI (Acute Open-label Period) LY2216684 + SSRI (Stabilization Open-label Period) LY2216684 + SSRI (Double-blind Randomized Withdrawal Period) Placebo + SSRI (Double-blind Randomized Withdrawal Period) LY2216684 + SSRI (Randomized Tapered Discontinuation Period) LY2216684 + SSRI (Randomized Abrupt Discontinuation Period) Placebo + SSRI (Abrupt Discontinuation Period) LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LY2216684 + SSRI (Acute Open-label Period) LY2216684 + SSRI (Stabilization Open-label Period) LY2216684 + SSRI (Double-blind Randomized Withdrawal Period) Placebo + SSRI (Double-blind Randomized Withdrawal Period) LY2216684 + SSRI (Randomized Tapered Discontinuation Period) LY2216684 + SSRI (Randomized Abrupt Discontinuation Period) Placebo + SSRI (Abrupt Discontinuation Period) LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
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   19/1244 (1.53%)      15/831 (1.81%)      2/294 (0.68%)      6/292 (2.05%)      2/128 (1.56%)      0/132 (0.00%)      2/267 (0.75%)      8/434 (1.84%)    
Cardiac disorders                 
Myocardial infarction  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Tachycardia  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Ventricular extrasystoles  1  0/1244 (0.00%)  0 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Gastrointestinal disorders                 
Abdominal pain upper  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Colitis ischaemic  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Intestinal obstruction  1  0/1244 (0.00%)  0 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Nausea  1  3/1244 (0.24%)  3 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Oesophageal spasm  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Vomiting  1  3/1244 (0.24%)  3 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
General disorders                 
Chest pain  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Infections and infestations                 
Diverticulitis  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Gastroenteritis  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Pneumonia  1  0/1244 (0.00%)  0 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Injury, poisoning and procedural complications                 
Intentional overdose  1  1/1244 (0.08%)  1 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Poisoning  1  0/1244 (0.00%)  0 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Road traffic accident  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Tendon rupture  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 1/294 (0.34%)  1 0/292 (0.00%)  0 1/128 (0.78%)  1 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Investigations                 
Blood creatine phosphokinase increased  1  1/1244 (0.08%)  1 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Blood glucose increased  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Metabolism and nutrition disorders                 
Dehydration  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Ketosis  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Intervertebral disc disorder  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Osteoarthritis  1  1/1244 (0.08%)  1 1/831 (0.12%)  1 0/294 (0.00%)  0 1/292 (0.34%)  1 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Angiomyolipoma  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 1/292 (0.34%)  1 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Breast cancer  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Cholesteatoma  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Metastases to liver  1  1/1244 (0.08%)  1 1/831 (0.12%)  1 0/294 (0.00%)  0 1/292 (0.34%)  1 0/128 (0.00%)  0 0/132 (0.00%)  0 1/267 (0.37%)  1 0/434 (0.00%)  0
Nervous system disorders                 
Convulsion  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Dizziness  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Encephalopathy  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Headache  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Hypoaesthesia  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Syncope  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Pregnancy, puerperium and perinatal conditions                 
Abortion  1  0/914 (0.00%)  0 1/641 (0.16%)  1 0/223 (0.00%)  0 0/226 (0.00%)  0 0/95 (0.00%)  0 0/105 (0.00%)  0 0/212 (0.00%)  0 0/307 (0.00%)  0
Blighted ovum  1  1/914 (0.11%)  1 0/641 (0.00%)  0 0/223 (0.00%)  0 0/226 (0.00%)  0 0/95 (0.00%)  0 0/105 (0.00%)  0 0/212 (0.00%)  0 1/307 (0.33%)  1
Psychiatric disorders                 
Alcohol abuse  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Depression  1  0/1244 (0.00%)  0 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Major depression  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 1/292 (0.34%)  1 1/128 (0.78%)  1 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Self injurious behaviour  1  1/1244 (0.08%)  1 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Suicidal behaviour  1  0/1244 (0.00%)  0 1/831 (0.12%)  2 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Suicidal ideation  1  0/1244 (0.00%)  0 1/831 (0.12%)  1 0/294 (0.00%)  0 1/292 (0.34%)  1 0/128 (0.00%)  0 0/132 (0.00%)  0 1/267 (0.37%)  1 0/434 (0.00%)  0
Suicide attempt  1  1/1244 (0.08%)  1 2/831 (0.24%)  2 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Renal and urinary disorders                 
Nephrolithiasis  1  1/1244 (0.08%)  1 1/831 (0.12%)  1 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Reproductive system and breast disorders                 
Vaginal polyp  1  0/914 (0.00%)  0 1/641 (0.16%)  1 1/223 (0.45%)  1 0/226 (0.00%)  0 0/95 (0.00%)  0 0/105 (0.00%)  0 0/212 (0.00%)  0 0/307 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                 
Dyspnoea  1  0/1244 (0.00%)  0 0/831 (0.00%)  0 0/294 (0.00%)  0 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Surgical and medical procedures                 
Hysterectomy  1  0/914 (0.00%)  0 1/641 (0.16%)  1 0/223 (0.00%)  0 0/226 (0.00%)  0 0/95 (0.00%)  0 0/105 (0.00%)  0 0/212 (0.00%)  0 0/307 (0.00%)  0
Vascular disorders                 
Hypertension  1  2/1244 (0.16%)  2 0/831 (0.00%)  0 0/294 (0.00%)  0 1/292 (0.34%)  1 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LY2216684 + SSRI (Acute Open-label Period) LY2216684 + SSRI (Stabilization Open-label Period) LY2216684 + SSRI (Double-blind Randomized Withdrawal Period) Placebo + SSRI (Double-blind Randomized Withdrawal Period) LY2216684 + SSRI (Randomized Tapered Discontinuation Period) LY2216684 + SSRI (Randomized Abrupt Discontinuation Period) Placebo + SSRI (Abrupt Discontinuation Period) LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
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   505/1244 (40.59%)      112/831 (13.48%)      37/294 (12.59%)      21/292 (7.19%)      9/128 (7.03%)      4/132 (3.03%)      16/267 (5.99%)      32/434 (7.37%)    
Gastrointestinal disorders                 
Constipation  1  132/1244 (10.61%)  134 14/831 (1.68%)  14 4/294 (1.36%)  5 2/292 (0.68%)  2 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 0/434 (0.00%)  0
Dry mouth  1  80/1244 (6.43%)  81 10/831 (1.20%)  10 3/294 (1.02%)  3 0/292 (0.00%)  0 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 1/434 (0.23%)  1
Nausea  1  147/1244 (11.82%)  155 18/831 (2.17%)  21 7/294 (2.38%)  7 5/292 (1.71%)  5 3/128 (2.34%)  3 1/132 (0.76%)  1 5/267 (1.87%)  6 8/434 (1.84%)  10
Nervous system disorders                 
Dizziness  1  83/1244 (6.67%)  86 8/831 (0.96%)  8 3/294 (1.02%)  3 4/292 (1.37%)  4 1/128 (0.78%)  1 1/132 (0.76%)  1 4/267 (1.50%)  4 4/434 (0.92%)  4
Headache  1  111/1244 (8.92%)  128 53/831 (6.38%)  54 18/294 (6.12%)  24 13/292 (4.45%)  13 7/128 (5.47%)  10 4/132 (3.03%)  5 11/267 (4.12%)  16 24/434 (5.53%)  30
Skin and subcutaneous tissue disorders                 
Hyperhidrosis  1  215/1244 (17.28%)  228 23/831 (2.77%)  24 8/294 (2.72%)  8 1/292 (0.34%)  1 0/128 (0.00%)  0 0/132 (0.00%)  0 0/267 (0.00%)  0 5/434 (1.15%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01299272     History of Changes
Other Study ID Numbers: 11317
H9P-MC-LNBN ( Other Identifier: Eli Lilly and Company )
First Submitted: February 16, 2011
First Posted: February 18, 2011
Results First Submitted: February 17, 2018
Results First Posted: April 17, 2018
Last Update Posted: April 17, 2018