The purpose of this study is to assess whether LY2216684 is superior to placebo in the treatment of adult patients with major depressive disorder.

• Drug: LY2216684
  Flexible Dosing: 6 mg, 9 mg, 12 mg and 18 mg (3 tablets) administered QD for up to 62 weeks
  Other Name: LY2216684
• Drug: Placebo
  Dose: 3 tablets QD for 62 weeks

• 1: Experimental
  Intervention: Drug: LY2216684
• 2: Placebo Comparator
  Intervention: Drug: Placebo

Inclusion Criteria:

• Adults age 18-65 years
• Meet criteria for MDD as defined by DSM-IV-TR criteria without psychotic features
• Women of child-bearing potential must test negative for pregnancy and agree to use a reliable method of birth control
• Grid Hamilton Rating Scale for Depression (GRID-HAMD17) total score >=18 at visit 1 and visit 2
• CGI-S score >=4 at visit 1 and visit 2

Exclusion Criteria:

• Are currently involved in or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug
• Have previously completed or withdrawn from this study or any other study investigating LY2216684
• Have had or currently have any additional ongoing DSM-IV-TR Axis 1 condition other than MDD
• Have had any anxiety disorder preceding the onset of depression that was considered the primary diagnosis within 1 year of visit 1
• Have an Axis II disorder which would interfere with compliance with the protocol
• Have a current or previous diagnosis of Bipolar I or II, psychotic depression, schizophrenia or other psychotic disorder
• Have a history of substance abuse within the past 1 year
• Women who are pregnant or breast-feeding
• Have had a lack of response of the current depressive episode to 2 or more adequate courses of antidepressant therapy, or in the judgement of the investigator considered to have treatment resistant depression
• Patients who are judged to be at serious suicidal risk
• Have a serious or unstable medical illness
• Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia or tachyarrhythmia, narrow angle glaucoma, or urinary hesitation or retention
• Have received treatment with a MAOI within 14 days prior to visit 1
• Have a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions
• Have a history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or psychosurgery within the last year
• Have a history of any seizure disorder (other than febrile seizures)
• Require psychotropic medication other than sedative/hypnotic medication for sleep
• Have a thyroid stimulating hormone (TSH ) level outside the established reference range.
• Are taking or have received treatment with any excluded medication within 7 days prior to visit 2
• Initiation or change in intensity of psychotherapy or other non-drug therapies within 6 weeks prior to enrollment
• A positive urine drug screen for any substance of abuse at visit 1
• Have initiate or discontinued hormone therapy within the previous 3 months prior to enrollment