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

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