A Study of the Neurobiology of Depression

Inclusion Criteria

Major Depressive Disorder (MDD) participants:

• Are right-handed
• Meet criteria for single episode or recurrent MDD, without psychotic features, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and confirmed by Structured Clinical Interview for DSM-IV-TR (SCID-IV), without co-morbid DSM-IV Axis I or II disorder at screening
• Be free of current antidepressant medication for a minimum of 6 weeks for fluoxetine treatment or of 4 weeks of other antidepressant treatment
• Have a 17-item Hamilton Depression Rating Scale (HAMD17) total score of ≥18 at screening, and baseline
• Women of child-bearing potential must have negative urine pregnancy tests prior to enrollment and agree to use a reliable method of birth control during the study

Healthy Participants

• Are right-handed
• Have a HAMD17 total score of <7 at screening and baseline and must not meet the criteria for MDD based on the SCID-IV

Exclusion Criteria

MDD participants and healthy participants:

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device
• Treatment within the last 30 days with a drug that has not received regulatory approval
• Have previously completed or withdrawn from this study or any other study investigating duloxetine
• Have a history of substance abuse or dependence within the past 6 months
• A positive urine drug screen for any substances of abuse or dependence
• Have any current DSM-IV-TR co-morbid Axis I or II disorder as determined by participant's history or investigator assessment
• Have any history of bipolar disorder, a primary psychotic disorder (schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder), known Alzheimer's disease or mental retardation, or obsessive-compulsive disorder as determined by participant's history or investigator assessment
• Pregnant women, women who are breast-feeding, or women of childbearing potential who are not using a medically accepted means of contraception when engaging in sexual intercourse or have been surgically sterilized
• Are judged by the investigator to have serious suicidal risk or risk of self-harm
• Have a history of recurrent self-mutilation or self-harm
• Have uncontrolled narrow-angle glaucoma
• Have been diagnosed with an acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C)
• Have end-stage renal disease, a prior renal transplant, current renal dialysis, or severe renal impairment
• Have abnormal thyroid-stimulating hormone (TSH) concentration
• Have had electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or vagus nerve stimulation (VNS) within the past year
• Initiating psychotherapy within 6 weeks prior to study entry or during study participation, stopping, or changing psychotherapy after study entry
• Have frequent and/or severe allergic reactions with multiple medications, or known allergic reactions to the study medication
• Known hypersensitivity to duloxetine or any of the inactive ingredients
• Lack of response of the current episode to two or more adequate courses of antidepressant therapy at a clinically appropriate dose for a minimum of 4 weeks or in the judgment of the investigator the participant meets criteria for treatment-resistant depression
• Known human immunodeficiency virus (HIV) and other medical disorders that are known to affect central nervous system (CNS) structures or function as assessed by the investigator (for example, CNS neoplasms, neurosyphilis)
• Have a medical illness, a clinically significant laboratory abnormality, or is taking a CNS active medication that, in the opinion of the investigator, might interfere with study participation (for example, is likely to require hospitalization) or that, in the opinion of the investigator, might interfere with the interpretation of the primary endpo