DBS for TRD With the Medtronic Summit RC+S

Inclusion Criteria:

• Age 25-70 years old.

• Ability to provide written informed consent.

• Lives within commuting distance to New York City and study location (Mount SinaiWest Hospital)

• Primary psychiatric diagnosis of Major Depressive Disorder (MDD), either singleepisode or recurrent type, without psychotic features, currently experiencing aMajor Depressive Episode (MDE), as diagnosed by Structured Clinical Interview forDSM IV-TR (SCID). Two independent psychiatrists will confirm the diagnosis.

• Current depressive episode of at least two years duration OR a history of more than 3 lifetime depressive episodes.

• Minimum score at study entry of 20 on the 17-item Hamilton Depression Rating Scale (HDRS-17)

• Average pre-operative HDRS-17 score of 20 or greater (averaged over four weeklypre-surgical evaluations during the four weeks prior to surgery) and an averagepre-operative HDRS-17 score no more than 30% lower than the baseline screeningHDRS-17 score.

• A maximum Global Assessment of Functioning of 50 or less.

• Confirmed to have treatment-resistant depression (TRD). Treatment-resistance will bedefined as:

1. Failure to respond to a minimum of four different antidepressant treatments (including at least three medications from at least three different drugclasses), evidence-based psychotherapy, or electroconvulsive therapy (ECT)administered at adequate doses and duration during the current episode. We willrequire documentation (i.e., statement from the treating psychiatrist) that atreatment trial has failed (either no response to maximum tolerable doses for aminimum of 4 weeks, or side effects at sub-maximal doses) as coded by a revisedAntidepressant Treatment History Form (ATHF). The study investigators willconfirm each treatment via review of records from referring psychiatristsand/or pharmacy records.

2. Failure or intolerance of an adequate course of electroconvulsive therapy (ECT)during any episode (confirmed by medical records) or not receiving ECT due to areason considered valid by the study psychiatrist. Such reasons might includelack of availability of ECT providers in the patient's location, concernregarding the impact of cognitive side effects of ECT on current ability towork or function, or inability to obtain third-party payment for ECT.Additionally, it is recognized that the probability that a patient who hasfailed four medications in the current episode will achieve a lasting responsewith ECT is about 18% (60% probability of an acute response and 30% ofmaintaining response for at least 24 weeks); patients who have refused ECTbecause they feel the chance of benefit does not outweigh the risks associatedwith ECT will be considered eligible.

• Able to undergo preoperative MRI

• Have a designated caregiver available to assist in compliance with study procedures

• Willing and able to comply with all study-related appointments and procedures

Exclusion criteria:

• Other Axis I comorbid conditions

• Active suicidal ideation with intent, suicide attempt within the last six months,more than three suicide attempts within the last two years, or serious suicide riskas determined by the study psychiatrists

• Other primary neurological disorders or unstable medical illness

• Conditions requiring anticoagulant therapy which cannot be discontinued for theperioperative period, as required

• Conditions requiring MRI scans or diathermy

• Pregnancy or plan to come pregnant during the study

• Contraindications for general anesthesia, neurosurgery, or an MRI scan

• Currently implanted with a cardiac pacemaker / defibrillator or other implantedelectrical device which may interfere with DBS stimulator or the function of whichmay be impacted by its implantation.

• Patients who lack the capacity for proper device usage and maintenance, in theopinion of the research team