Clinical trial from which subjects were recruited closed to enrollment

This is an ancillary study to a clinical trial that is being conducted at Massachusetts General Hospital. Investigators at MGH are conducting a clinical trial to test the efficacy of ziprasidone together with escitalopram for treatment-resistant depression (NCT00633399). This observational study will involve magnetic resonance scans to examine brain chemistry (neurotransmitter levels), brain activity, and functional connections between brain regions before and after participating in the trial. The neurotransmitters of interest are glutamate, glutamine, and GABA. Comparisons will be made between individuals who receive ziprasidone and individuals who receive an inactive placebo. Differences between participants who respond to standard antidepressants and those who require additional medication will also be examined. All participants will have a baseline magnetic resonance scan before starting medication. The second scan will be after 8 weeks of escitalopram treatment for those who respond or following 8 weeks of escitalopram plus ziaprasidone or placebo (16 weeks after starting) for those who do not respond to escitalopram alone. Participants will complete standard rating scales for depression at each visit.

Inclusion Criteria:

• Aged 18-65
• Meets DSM-IV criteria for major depressive disorder
• Meets eligibility criteria for clinical trial of ziprasidone augmentation of escitalopram
• Capable of providing informed consent

Exclusion Criteria:

• Meets exclusion criteria for augmentation clinical trial protocol
• Pregnancy or unwillingness to avoid pregnancy during trial
• Current or past psychosis or bipolar disorder
• Substance abuse or dependence in the past six months
• Clinically significant suicidality
• Unstable cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizures
• Use of a concomitant medication that acts on glutamate or GABA neurotransmission
• Contraindication to magnetic resonance imaging (metal implant or device, occupational metal exposure, significant claustrophobia)

Participants in a clinical trial for treatment-resistant depression who agree to have magnetic resonance scans