The objective of the current study is to investigate the safety and efficacy of a single dose of intranasal (IN) ketamine in treatment-resistant depression (TRD).

Inclusion Criteria:

1. Male or female patients, 21-65 years;
2. Women of childbearing potential must agree to use a medically accepted means of contraception for the duration of the study;
3. Primary diagnosis of major depressive disorder as assessed by the SCID-P;
4. Current depressive episode;
5. History of a failure to respond to at least one (1) adequate pharmacotherapy trials in the current major depressive episode;
6. Subjects must have scored ≥ 30 on the IDS-C30 at Screening ≥ 24 at Treatment Day #1 and #2;
7. Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
8. Subjects must be able to identify a family member, physician, or friend who will participate in the Treatment Contract and serve as an emergency contact.

Exclusion Criteria:

1. Women who plan to become pregnant, are pregnant or are breast-feeding;
2. Any unstable medical illness including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease;
3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
4. Lifetime history of schizophrenia, schizoaffective disorder, bipolar disorder, OCD, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
5. Drug or alcohol abuse or dependence within the preceding 6 months;
6. Lifetime abuse or dependence on ketamine or phencyclidine;
7. Patients judged by study investigator to be at high risk for suicide.
8. Previous participation in a ketamine study at Mount Sinai

one participant data information missing for history of Psychotherapy, and history of Failed Antidepressant Medications.

within 24 hours following treatment

No serious adverse events occurred during the study.

Small sample size. Ongoing treatment with psychotropic medication allowed at stable doses makes it difficult to distinguish an intrinsic effect of ketamine from benefits resulting from the combination of ketamine with other antidepressant agents.