A Study of Flexible or Fixed Dose LY2216684 as Adjunctive Treatment for Participants With Major Depressive Disorder Who Have Had a Partial Response to Selective Serotonin Reuptake Inhibitor (SSRI) Treatment

Following the Confirmation (CF) Phase, participants were randomized to adjunctive LY2216684
or adjunctive placebo if they had <25% improvement in the Montgomery-Åsberg Depression Rating
Scale (MADRS) total score over the past 3 weeks and a current MADRS total score ≥14.
Participants who did not meet criteria received adjunctive placebo to preserve the blind.

Inclusion Criteria:

- Clinical diagnosis of Major Depressive Disorder (MDD)

- Using a reliable method of birth control

- Are taking a selective serotonin reuptake inhibitor (SSRI) approved for MDD treatment
within the participant's country and the SSRI prescribed, including dose, should be
consistent with labeling guidelines within the participating country

- Have a partial response to SSRI treatment

- Meet inclusion scores on pre-defined psychiatric scales to assess diagnosis of
depression, disease severity, and response to SSRI treatment

- Reliable and able to keep all scheduled appointments

Exclusion Criteria:

- Presence of another primary psychiatric illness:

- Have had or currently have any additional ongoing Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition, Text Revision (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,
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 an Axis II disorder that, in the judgment of the investigator, would
interfere with compliance with protocol

- Have any diagnosed medical condition that could be exacerbated by noradrenergic
agents, including unstable hypertension, unstable heart disease, tachycardia,
tachyarrhythmia, narrow-angle glaucoma, and history of 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 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

- Enrollment in a clinical study for an investigational drug

- Serious or unstable medical condition

- History of seizure disorders

- Have initiated psychotherapy, change in intensity of psychotherapy or other nondrug
therapies (such as acupuncture or hypnosis) within 6 weeks prior to enrollment or any
time during the study

- Participants who, in the opinion of the investigator, are judged to be at serious risk
for harm to self or others