A Safety Study in Participants With Major Depressive Disorder

Inclusion Criteria

• Adults competent and able to give informed consent
• 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
• Participants who are being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and 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 the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria
• Meet criteria for partial response, as defined by investigator's opinion that participant has experienced a minimal clinically meaningful improvement with SSRI
• Have a Grid Hamilton Rating Scale for Depression (GRID-HAMD17) total score greater than or equal to 16 at screening
• Have less than or equal to 75 percent improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Response Questionnaire (MGH-ATRQ)
• Meet all other inclusion criteria per protocol

Exclusion Criteria

• Presence of another primary psychiatric illnesses:
• Have had or currently have any additional ongoing DSM-IV-TR Axis I 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, post-traumatic stress disorder, generalized anxiety disorder, 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 1 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine
• Have a DSM-IV-TR 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 which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, urinary hesitation or retention
• Use of excluded concomitant or psychotropic medication other than SSRI
• Have initiated or discontinued hormone therapy within the previous 3 months of prior to enrollment
• History of treatment resistant depression as shown by:
• Have had 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 history of electroconvulsive therapy, transcranial magnetic stimulation, or psychosurgery within the last year
• Meet any other exclusion criteria per protocol