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 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.