Neurobiological Bases of Placebo Response in Major Depressive Disorder

Inclusion Criteria: * Meets diagnostic criteria for Major Depressive Disorder * Written informed consent * Men or women aged 18-60 years old * A score of 18 or greater on the HAMD-28 * Patient must continue to meet criteria for current MDD at baseline. Patients must have Clinical Global Impression Improvement (CGI) scores ≥ 3 (i.e. minimally improved or less) from the screen to the baseline visit * Agreeing to, and eligible for all procedures (only patients 18-45 will be eligible for MR-PET study) Exclusion Criteria: * Pregnant women or women of child bearing potential not using a medically accepted means of contraception * Patients who are a serious suicide or homicide risk * Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, uncontrolled seizure disorder * The following DSM-IV diagnoses: a) organic mental disorders b) substance use disorders, including alcohol, active within the last year; c) schizophrenia; d) delusional disorder; e) psychotic disorders not elsewhere classified; f) bipolar disorder; g) acute bereavement; h) borderline or antisocial personality disorder i) current primary diagnoses of panic disorder, social phobia, GAD, or OCD (disorders that present as chief complaint and/or have their onset preceding the onset of MDD), l) Patients with mood congruent or mood incongruent psychotic features * Currently taking any of the following exclusionary medications: antipsychotics, anticonvulsants, mood stabilizers, stimulants, antidepressants, potential antidepressant augmenting agents (e.g., T3, SAMe, St. John's Wort, lithium, buspirone, Omega 3 fatty acids). If it is determined that it is safe to discontinue a medication, the patient will be required to wait a period equivalent to at least 5 half lives of the drug before the screening * Patients who have taken an investigational psychotropic drug within the last year * Patients who have not responded to one or more antidepressant trials of adequate doses (e.g., fluoxetine 40 mg/day or higher) and duration (e.g., for six weeks or more) over the past five years, as defined by the MGH-ATRQ * History of inadequate response or poor tolerability to citalopram or escitalopram * Any concomitant form of psychotherapy (depression-focused) * Receiving or have received during the index episode Vagal nerve stimulation, ECT or rTMS, or other somatic antidepressant treatments * Any reason not listed, determined by the site PI or study clinician, constituting good clinical practice and making participation in the study hazardous * Contraindications to fMRI scanning and MR-PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia) * MR-PET-specific exclusion criteria: Patients who are younger than 18 or older than 45 years of age