A Study of the Neurobiology of Depression
Condition: Major Depressive Disorder; Healthy Participants
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Duloxetine
Intervention description: 60 milligrams (mg) administered orally daily for 8 weeks then 60-120 mg if non remitter or 60 mg if remitter for 4 additional weeks
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 25 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Previous research studies have shown that depression is associated with changes in structure
      and activity in different parts of the brain and that antidepressant medication can affect
      brain activity in different parts of the brain in individuals suffering from depression. The
      primary purpose of the study is to find out more about how the antidepressant medication
      duloxetine affects brain activity and structure in individuals with depression.
    

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