LY2216684 is being studied as adjunctive treatment for major depressive disorder (MDD) in participants who are partial responders to selective serotonin reuptake inhibitors (SSRIs). Sertraline is a medication that is widely used to treat MDD and is a known substrate of cytochrome P450s (CYP450s), including CYP450 2D6 (CYP2D6), CYP450 2C19 (CYP2C19), CYPP450 3A4 (CYP3A4), and a modest inhibitor of CYP2D6. Based on the diversity of hepatic metabolic clearance pathways for LY2216684 and its elimination by the kidney, it is expected that CYP2D6 inhibition by sertraline will not result in a substantial change in the pharmacokinetic (PK) profile of LY2216684. LY2216684 is only known to be a moderate inhibitor of CYP2C19, so it is unlikely that coadministration of sertraline with LY2216684 will result in a clinically meaningful change in the PK of sertraline. This study is being conducted to test these hypotheses.

Inclusion Criteria:

• Are overtly healthy as determined by medical history and physical examination.
• Male participants - Agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug.
• Female participants - 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 + 1 month following the last dose of study drug; or are women not of child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone (FSH) level ≥40 mass International Units per milliliter (mIU/mL).
• Body mass index (BMI) up to 32.0 kilograms per square meter (kg/m^2).
• 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 according to the protocol.
• Have normal blood pressure and pulse rate (supine position and standing) as determined by the investigator.
• Are reliable and willing to be available for the duration of the study and willing to follow study procedures.
• Provided 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/intolerance to LY2216684, sertraline, or related compounds.
• Are persons who previously completed or discontinued from this study, or any other study investigating LY2216684 within 6 months prior to screening.
• Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) as determined by the investigator.
• Have significant history of or current cardiovascular (including dysrhythmias), respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders 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 a history of seizure disorders.
• Have a history or presence of the signs and/or symptoms of hyponatremia.
• Have a history or presence of the signs and/or symptoms of hyperthyroidism as determined by an abnormal thyroid stimulating hormone (TSH) at screening.
• Have a history or presence of the signs and/or symptoms of urinary retention or benign prostatic hypertrophy.
• Show evidence of significant active neuropsychiatric disease or a history of suicidal thoughts or suicide attempt.
• 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.
• Intend to use over-the-counter or prescription medication within 14 days prior to dosing unless deemed acceptable by the investigator and sponsor's medical monitor.
• Have donated blood of more than 500 milliliters (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 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 participants unwilling to adhere to study caffeine restrictions.
• Have used any tobacco-containing or nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment.
• Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment and during the study.
• Have a documented or suspected history of glaucoma.
• Participants determined to be unsuitable by the investigator for any reason.