Intervention: Duloxetine
Trial phase: Phase 4
ATC code: N06AX21
SMILES: CNCC[C@H](Oc1cccc2ccccc12)c1cccs1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 32
Group description: Duloxetine: Participants with major depressive disorder (MDD) received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters [defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score >7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose.
Eligibility criteria:
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Have previously completed or withdrawn from this study or any other study investigating duloxetine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 endpoint (for example, hypertension or diabetes)
Are unwilling or unable to comply with the study procedures