The purpose of this study is to explore benefits of duloxetine in enhancing psychological resilience and to understand the relevance of inhibiting of both serotonin (5HT) and norepinephrine (NE)to therapeutic responses.

This is an investigator-initiated, single-site study consisting of 8 weeks of open-label, fixed-dose treatment with duloxetine (30mg-60mg/day) in patients with Major Depressive Disorder (MDD).

Inclusion Criteria:

• ages 18-65
• primary diagnosis of MDD based on Diagnostic Standard Manual(DSM-IV) criteria and assessed by the MINI International Neuropsychiatric Interview
• Montgomery-Asberg Depression Rating Scale (MADRS)score of at least 20 on baseline
• Minimum Clinical Global Impressions of Severity (CGS) severity score of 4
• Ability to provide written consent form
• A negative serum pregnancy test for women of childbearing potential

Exclusion Criteria:

• Current DSM-IV diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, mental retardation or other pervasive developmental disorder or cognitive disorder due to a general medical condition
• History of substance abuse or dependence within the last 6 months
• Suicide risk or serious suicide attempt within the last year
• Clinically significant medical condition or laboratory abnormality
• Women of childbearing potential who are unwilling to practice an acceptable method of contraception
• Subjects needing concurrent use of psychotropic medications
• History of sensitivity to duloxetine
• History of failure to respond to an adequate trial of duloxetine (at least 60mg/day for 4 weeks)
• Subjects taking monoamine oxidase inhibitors (MAOIs)
• Subjects with uncontrolled narrow-angle glaucoma