Neurobiological Bases of Placebo Response in Major Depressive Disorder

We are doing this research study to find out if people who get better while taking a specific kind of antidepressant medication (a selective serotonin reuptake inhibitor, or SSRI) and people who get better while taking placebo (an inactive substance) have similar chemicals in their brains. Some participants may complete a procedure called Acute Tryptophan Depletion (ATD), which is a way to study the role of serotonin in depression. Some participants may also undergo a magnetic resonance-positron emission tomography (MR-PET) scan.


Eligibility Criteria:
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