A Study of LY2216684 in Major Depressive Disorder in Patients Taking Selective Serotonin Reuptake Inhibitors

Inclusion Criteria:

- Are patients that have been diagnosed with major depressive disorder (MDD) and are on
a stable dose of an selective serotonin reuptake inhibitor (SSRI) for at least 4 weeks
prior to enrollment, as determined by medical history and physical examination.

- Male patients: Agree to use a reliable method of birth control during the study and
for 3 months following the last dose of study drug.

- Female patients: Are women of child-bearing potential who test negative for pregnancy
at the time of enrollment, have used a reliable method of birth control for 6 weeks
prior to administration of study drug, and agree to use a reliable method of birth
control during the study and for 1 month following the last dose of study drug; or
Women not of child-bearing potential due to surgical sterilization (hysterectomy or
bilateral oophorectomy or tubal ligation) or menopause for at least 1 year without
menses or 6 months without menses and a follicle stimulating hormone (FSH) >40
milli-international-units/milliliter (mIU/mL).

- Have a body mass index (BMI) of up to 32.0 kilogram/squaremeter (kg/m2).

- Have normal blood pressure (BP) and pulse rate (systolic BP <140, diastolic BP <90;
supine position and standing) as determined by the investigator.

- Patients that have a diagnosis of hypertension but are well controlled on a stable
dose (at least 4 weeks of diuretic, angiotensin converting enzyme [ACE]-inhibitor, or
angiotensin 2 receptor inhibitor) are acceptable for inclusion in this study.
Allowance of a specific anti-hypertensive is per the investigator's discretion.

- Have screening clinical laboratory test results within normal reference range for the
population or investigator site, or results with acceptable deviations that are judged
to be not clinically significant by the investigator.

- Have venous access sufficient to allow blood sampling as per the protocol.

- Are reliable and willing to make themselves available for the duration of the study
and are willing to follow study procedures.

- Have given written informed consent approved by Lilly and the institutional review
board (IRB) governing the site.

Exclusion Criteria:

- Are currently enrolled in, or discontinued within the last 30 days from, a clinical
trial involving an investigational drug or device or off-label use of a drug or device
other than the study drug used in this study, or are concurrently enrolled in any
other type of medical research judged not to be scientifically or medically compatible
with this study.

- Have known allergies to any compound related to LY2216684.

- Are persons who have previously completed or withdrawn from this study or any other
study investigating LY2216684.

- Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) that,
in the opinion of the investigator, increases the risks associated with participating
in the study.

- Have a significant history of or presence of cardiovascular (including dysrhythmias),
respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or
neurological disorders, or any condition capable of significantly altering the
absorption, metabolism, or elimination of drugs; of constituting a risk when taking
the study medication; or of interfering with the interpretation of data.

- Have unequal BP (> 20 millimeter of mercury [mm Hg]) in the left arm versus right arm
(as measured with a BP cuff) or have absent or unequal radial pulses in either arm.

- Have a history of seizure disorders.

- Regularly use known drugs of abuse and/or show positive findings on urinary drug
screening.

- Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV
antibodies.

- Show evidence of hepatitis C and/or positive hepatitis C antibody.

- Show evidence of hepatitis B and/or positive hepatitis B surface antigen.

- Are women with a positive pregnancy test or women who are lactating.

- Use of over-the-counter or prescription medication (other than stable doses of SSRI as
noted above) with a narrow therapeutic index (including, but not limited to warfarin
or clopidogrel) or those that are known to have an effect on heart rate (e.g.,
beta-blockers) within 14 days prior to dosing.

- Use of any drugs or substances that are known to be a strong inducer or inhibitor of
cytochrome P450 2D6 (CYP2D6) or cytochrome P450 3A4 (CYP3A4) within 30 days prior to
check-in (study entry) and during the conduct of the study.

- Have donated blood of more than 500 milliliter (mL) within 4 weeks prior to screening.

- Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling
to stop alcohol consumption 48 hours prior to check-in (study entry)until the
completion of the study (1 unit = 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of
wine; 1.5 oz or 45 mL of distilled spirits).

- Consume 5 or more cups of coffee (or other beverages of comparable caffeine content)
per day, on a habitual basis, or any patients unwilling to adhere to study caffeine
restrictions.

- Patients must adhere to the smoking restrictions of the Clinical Research Unit (CRU)
while a resident of the CRU.

- Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment
or are unwilling to avoid during the study.

- Have a documented or suspected history of glaucoma.

- Patients determined to be unsuitable by the investigator for any reason.