A Study in Adult Patients With Major Depressive Disorder

Inclusion Criteria:

- Adults age 18-65 years

- 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 without psychotic features

- Women of child-bearing potential must test negative for pregnancy and agree to use a
reliable method of birth control

- Grid 17-item Hamilton Rating Scale for Depression (GRID-HAMD17) total score ≥18 at
Visit 1 and Visit 2

- Clinical global impressions of severity (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- Have previously completed or withdrawn from this study or any other study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 that would interfere with protocol compliance

- 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 judgment of the investigator, considered
to have treatment-resistant depression

- Participants 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 monoamine oxidase inhibitor (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 initiated or discontinued hormone therapy within the previous 3 months prior to
enrollment