Inclusion Criteria:
* 21-55 years of age. MDD currently depressed subjects will meet DSM-V criteria for MDD based on the Mini-International Neuropsychiatric Interview (MINI) (http://www.medicaloutcomes.com/index/mini7fororganizations) with a 17-item Hamilton Depression Rating Scale (HamD17) (Hamilton, 1960) score \> 17.
* Subjects must have failed to enter remission with at least two prior antidepressant medications in the current episode (Vasavada et al., 2016)
* Must have been free of any medications known to significantly affect brain function for at least ten days prior to enrollment (except fluoxetine, which will require a five-week washout).
Exclusion Criteria:
* No unstable medical illness that would prevent completion of participation in the trial (determined as needed from physical examination, ECG, laboratory safety tests, as well as a review of systems).
* Clinically significant physical abnormalities as indicated by physical examination, hematological laboratory assay, or urinalysis, defined as:
hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) \< 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) \< 2 x the upper limit of normal;
* A screening ECG that demonstrates anything other than normal sinus rhythm, normal conduction, and no clinically significant arrhythmias
* History of epilepsy, seizures, or severe head trauma;
* Resting vital signs on any study visit outside of acceptable parameters (i.e., pulse of 60-100 bpm, blood pressures of 90-150 mm Hg systolic, 50- 90 mm Hg diastolic);
* Any indication of suicidal ideation (e.g. as assessed by the suicidality question on the HamD17or the Columbia Suicide Severity Rating Scale.
* Baseline QT prolongation (QTc\> 450 ms): Given that citalopram has been found to be associated with a dose-dependent risk of ECG QT interval prolongation, in order to avoid the potential risk of causing ventricular arrhythmias including Torsades de Pointes, we will exclude participants from the study who exhibit baseline QTc prolongation.
* For women of childbearing age, a positive urine pregnancy test, as well as women who are currently breastfeeding or not using a medically acceptable method of birth control
* Presence of any implanted medical device or metal in the body that would render it unsafe to perform TMS or an MRI.
* Axis I: the presence of any other primary mood, anxiety, or psychotic disorder, depression secondary to a general medical condition, or substance- induced illness. Subjects also will be excluded if they have current suicidal intent or plan, a history of substance abuse or dependence within the past six months (except nicotine and caffeine), Bipolar Disorder or psychotic disorder (lifetime), eating disorder (current or within the past year), Obsessive Compulsive Disorder (lifetime), Post-Traumatic Stress Disorder (PTSD, current or within the past year);
* Axis III: active medical illness known to significantly affect brain function or that could be etiologically related to the ongoing depression (e.g., untreated hypothyroidism);
* Current treatment with a medication known to affect brain function. This would include both psychiatric and centrally-acting neurological agents.
The investigators have chosen to exclude these subjects because current medication could affect measures of brain function as well as introduce an uncontrolled treatment effect into the study. Prospective subjects who are currently taking psychiatric medications will also be excluded as the risk of antidepressant discontinuation outweighs the potential benefit of study participation. A history of prior treatment with IV CIT. We have chosen to exclude subjects who have received this treatment because they may have a degree of treatment resistance that would make it less likely for them to respond to treatment in the current protocol. Additionally, if they previously have received CIT the PBO treatment blind in the current protocol may not be effective;
* Current treatment with a medication known to affect brain function. We have chosen to exclude these subjects because current medication could affect measures of brain function as well as introduce an uncontrolled treatment effect into the study. These medications include: antidepressants, barbiturates, anticonvulsants/mood stabilizers, benzodiazepines, anticholinergics, herbal preparations, antipsychotics, muscle relaxants, antimigraine, psychostimulants, anti-Parkinsonian medications, sedating antihistamines, corticosteroids (oral; topical preparations OK), Zyban (bupropion for use in smoking cessation);
* Treatment with any of the following medications within the last 30 days prior to randomization: antidepressants, anticonvulsants, hypnotics, antipsychotics, psychomotor stimulants, anti-anxiety agents, or cimetidine;
* Current illicit drug use. We will perform urine toxicology screens at baseline;
* History of stroke, skull fracture, brain surgery, or transient ischemic attacks, or other brain disease that could affect results;
* For women of childbearing age, a positive urine pregnancy test, as well as women who are currently breastfeeding or not using a medically acceptable method of birth control;
* History of allergic reaction or intolerance to citalopram (any formulation); and,
* History of ECT within the past six months, or history of failure to benefit from prior TMS treatment of MDD.
