Trial of MR-guided Focused Ultrasound for Treatment of Refractory Major Depression

Inclusion Criteria:

1. Men and women ≥20 and ≤80 years of age.
2. Patients who are able and willing to give consent and physically and practically ableto attend study visits, as determined by both study Psychiatrist and the surgeon.
3. DSM-V diagnosis of major depressive episode, as a component of an Axis I disorder,such as Major Depressive Disorder, Bipolar Disorder, Anxiety Disorder, EatingDisorder, Substance Abuse/Dependence Disorder ,or Personality Disorder
4. At least 5-year illness history of the primary disorder and at least 6 months sincethe onset of the first episode of major depression.
5. A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed (patients with bipolar disorder may be rapid cycling, but have to have at least 2weeks of major depression at the time the HAMD is conducted)
6. Medication-refractoriness as determined by an adequate dose and duration of standardpsychiatric treatments (including psychotherapy and/or pharmacology) as determined bytwo psychiatrists associated with the study. Including specifically:
7. Failed to respond or tolerate adequate trial of three or more medicationsaccepted as first line in the treatment of depression
8. Failed to respond or tolerate augmentation with or combination,of at least 2medications known to be first line treatments for depression
9. An adequate trial of cognitive behavioural therapy or other evidence-supportedpsychotherapy, delivered by a therapist experienced in treating depression
10. Able to communicate sensations during the ExAblate MRgFUS treatment
11. A consistent dose of any and all medications in the 30 days prior to study entry.
12. Women of childbearing potential must agree to use a contraception method throughoutthe study.

Exclusion Criteria:

1. Patients with unstable cardiac status [e.g. Unstable angina pectoris on medication,Patients with documented myocardial infarction within six months, Congestive heartfailure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs,Severe hypertension (diastolic BP > 100 on medication)]
2. Patients with standard contraindications for MR imaging such as non-MRI compatibleimplanted metallic devices including cardiac pacemakers, size limitations, etc.
3. Severely impaired renal function (estimated glomerular filtration rate < 30ml/min/1.73m2) or receiving dialysis
4. Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy, includingrisk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal INR)
5. Cerebrovascular disease (e.g. CVA within 6 months) or history of intracranialhemorrhage
6. Untreated, uncontrolled sleep apnea
7. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy withinone week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
8. Individuals who are not able or willing to tolerate the required prolonged stationarysupine position during treatment
9. Are participating or have participated in another clinical trial in the last 30 days
10. Patients unable to communicate with the investigator and staff.
11. Presence of significant cognitive impairment
12. Presence of psychosis on clinical evaluation.
13. Patients with brain tumors already known or revealed on pretreatment MRI
14. Currently pregnant (as determined by history and serum HCG) or lactating.