There are many common pharmacological treatments for major depression disorder (MDD), however the efficacy of these drugs often fails in severe cases. Intravenous (IV) administered ketamine may offer the potential for remission of the symptoms in patients with MDD; however it has not yet been approved by FDA for this purpose. This study will make use of an electroencephalography (EEG) machine to measure the brain's activity and response while the IV ketamine is being delivered. The objective of this study is to characterize the change in EEG response of patients with MDD, during and 4 weeks after a course of IV ketamine infusions.

This study will enroll 35 patients with major depressive disorder. Candidates for participation in the study will typically be either referred to the clinic through their healthcare provider or will have sought out participation on their own accord based on advertising. Subjects will be screened for eligibility and suitable patients will be invited to attend a screening visit in the clinic and complete informed consent.

Upon determining eligibility, subjects will have their first treatment session booked within 42 days of screening (Baseline, visit 0). Three subsequent weekly (±3 days) ketamine therapy treatment sessions will occur on days 7, 14 and 21, for a total of four ketamine infusions over four weeks. All patients will return for a follow-up visit at 4-weeks post final treatment visit, day 49.

Inclusion Criteria:

1. Individuals between 18 and 70 years of age, inclusive
2. Adult patients with a documented primary Axis I clinical diagnosis meeting criteria from the DSM-V for a major depressive disorder
3. Score of <15 on the DES
4. Moderate to severe symptoms objectively documented using MADRS total score of ≥ 20
5. Ability to maintain scheduled appointments for screenings, 4 treatment visits and follow-up EEG visit.
6. History of major depressive disorder.
7. Females of child-bearing potential who are sexually active must agree to use two forms of contraception. A pregnancy test will be performed before the first treatment.
8. Must have stable residence address, internet and mobile phone.
9. Must speak fluent English.

Exclusion Criteria:

1. Known allergy to ketamine or any other drug used in the study.
2. Use of ketamine in a therapeutic model within the preceding 12 months of the study.
3. Current or any history of schizoaffective disorder(s).
4. Score of ≥ 15 on DES
5. History of illicit active substance abuse or dependence including ketamine as determined on by the SCID-5-CT and/or drug urine screening during study visits.
6. Pregnancy, breastfeeding or desire to become pregnant during the course of the study.
7. Serious, unstable illnesses including, but not limited to; hepatic, gastro-intestinal, respiratory, cardiovascular (including ischemic heart disease and coronary heart disease). History of ischemic stroke, atrial fibrillation, severe endocrinological, neurological, immunological or hematological disease.
8. Any history of cerebral vascular events including stroke, bleeding into the brain and subdural hematomas.
9. Any implantable metallic device(s) or implant(s) above the level of shoulders.
10. Any non-removable metallic piercings.
11. Patients with cochlear implants and non-removable hearing aids.
12. Current use of: Dilantin, Depakote, Phenobarbital, Gabapentin, Pregabalin and Benzodiazepines. Certain candidates with long use of Benzodiazepines may qualify at PI's discretion.
13. Severe labile hypertension.
14. Significant uncontrolled hypertension (i.e., SBP > 150 mmHG, DBP > 100 mmHG)
15. Uncontrolled diabetes mellitus.
16. Patients on renal dialysis.
17. Inability to achieve consistent IV access.