Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intranasal (IN) Ketamine in Treatment-Resistant Depression (TRD)
Brief Summary: 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).


Options:
A: Inclusion Criteria:

* Male or female patients between 18 and 85 years of age at screening.
* Patients must provide written informed consent prior to study entry.
* Patients must meet DSM-IV-TR (Diagnostic and Statistical Manual IV Text Revision) criteria for Major Depressive Episode of a severity mild, moderate or severe or in partial remission, as confirmed by the MINI.
* Patients must have a HAM-D (17-item) score of 16 or higher.
* Patients must have been on 1 of the following medications for 4 or more weeks at or above the listed dose with no psychiatric medication dose changes for the past 25 days:

  * 20 mg qD of fluoxetine (Once Daily)
  * 50 mg qD of sertraline
  * 20 mg qD of paroxetine
  * 200 mg qD of fluvoxamine
  * 20 mg qD of citalopram
  * 10 mg qD of escitalopram
  * 150 mg qD of venlafaxine or venlafaxine sustained release
  * 300 mg qD of bupropion or bupropion sustained or extended release
  * 15 mg qD of mirtazapine
  * 60 mg qD of duloxetine
* Participants must agree to keep the dose of their existing antidepressant(s) constant throughout the 8-week trial.

Exclusion Criteria:

* Diagnosis of bipolar disorder or schizophrenic or schizoaffective disorder.
* History of alcohol or drug abuse or dependence within 6 months of enrollment.
* Patients who have received ECT (Electroconvulsive Therapy) in the past 3 months.
* History of seizures.
* Moderate dementia (MMSE score of 20 or less).
* Active suicidal ideation: endorsing a 3 (most severe score) on QIDS-SR (Quick Inventory of Depression Symptomatology Self Reports) suicide item OR a score of 2 or higher for the past week on Suicide Scale items 4 or 5 (current suicidal ideation moderate or strong or would avoid taking steps to save life).
* Currently taking a mood stabilizer or antipsychotic (except lithium clearly used as an augmenting agent).
* Patients who, in the opinion of the investigator, might not be suitable for the study.
B: Inclusion Criteria:

* Female who is non-pregnant, nonlactating, using an acceptable method of birth control, or is not of child-bearing potential;
* be diagnosed with current major depressive disorder either mild or severe, as evidenced by a score of at least 9 but not more than 20 on the Quick Inventory of Depression Symptomatology - Clinician Rated (QIDS-C);
* be anti-depressant naïve;
* be able to refrain from all use of grapefruit containing products from the time of admission until the last assessment is performed at discharge;
* smokes less than or equal to 10 cigarettes or equivalent daily.

Exclusion Criteria:

* has any current and primary Axis I disorder other than major depressive disorder;
* has any history of bipolar I or II disorder, dysthymia, psychotic depression, psychotic disorders, posttraumatic stress disorder, borderline personality disorder, obsessive compulsive disorder, or eating disorder;
* the duration of the current depressive episode is longer than 2 years at screening;
* has any history of a significant suicide attempt, or poses a current risk of attempting suicide;
* is known to be human immunodeficiency virus (HIV) positive, or positive for hepatitis B surface antigen or hepatitis A antibodies or hepatitis C total antibodies;
* has any clinically significant concurrent endocrine, renal, respiratory, cardiovascular, hematological, immunological, cerebrovascular, neurological, malignancy, or any other concurrent medical condition, or has any history of diabetes mellitus;
* donation of blood within 60 days prior to the anticipated first dose of trial medication.
C: 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
D: Inclusion Criteria:

* At the time of signing the informed consent form (ICF), participant must be a man or woman 18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than \[\>\]18) to 64 years of age, inclusive
* At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single-episode MDD, the duration must be greater than or equal to \[\>=\] 2 years) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI)
* At the start of the screening/prospective observational phase, participant must have an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of greater than or equal to (\>=) 34
* At the start of the screening/prospective observational phase, participant must have had non-response (greater than or equal to \[\<=25\] percent \[%\] improvement) to ≥1 but less than or equal to (\<=) 5 (if current episode is \>2 years, upper limit is applicable to only the last 2 years) oral antidepressant treatments in the current episode of depression, assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented by medical history and pharmacy/prescription records, for the current episode of depression. In addition, the participant is taking a different oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2 weeks at or above the minimum therapeutic dose
* The participant's current major depressive episode, depression symptom severity (Week 1 MADRS total score \>=28 required), and antidepressant treatment response in the current depressive episode, must be confirmed using a Site Independent Qualification Assessment

Exclusion Criteria:

* Participants who have previously demonstrated nonresponse of depressive symptoms to esketamine or ketamine in the current major depressive episode, to all 4 of the oral antidepressant treatment options available for the double-blind induction phase (ie, duloxetine, escitalopram, sertraline, and venlafaxine extended release \[XR\]) in the current major depressive episode (based on MGH-ATRQ), or an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
* Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
* Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychosis, bipolar or related disorders (confirmed by the MINI), comorbid obsessive compulsive disorder, intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
* Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening/prospective observational phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)
* Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria

Answer: C