Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Subjects Who Are Assessed to be at Imminent Risk for Suicide
Brief Summary: The purpose of this study is to evaluate the efficacy of intranasal esketamine 84 milligram (mg) compared with intranasal placebo along with standard care treatment, in reducing the symptoms of major depressive disorder (MDD) (an affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities, the mood disturbance is prominent and relatively persistent), including the risk for suicide as assessed by the Investigator, in participants who will be assessed to be at imminent risk for suicide.


Options:
A: Inclusion Criteria:

A subject will be eligible for inclusion only if all of the following criteria are met:

1. Male or female, 18 to 70 years of age, inclusive, at screening.
2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
3. Diagnosed with Major Depressive Disorder (MDD), single or recurrent, and currently experiencing a Major Depressive Episode (MDE) of at least eight weeks in duration, prior to screening, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR™). The diagnosis of MDD will be made by a site psychiatrist and supported by the Structured Clinical Interview for DSM-IV-TR™ (SCID-I/P) or the M.I.N.I International Neuropsychiatric Interview a short, structured psychiatric interview.
4. Has a history of TRD during the current MDE, as assessed by the investigator. TRD is defined as failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms), as perceived by the participant, to at least two "treatment courses" of a therapeutic dose of an antidepressant therapy of at least 8 weeks duration. The adequacy of dose and duration of the antidepressant therapy will be determined as per the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ) criteria. Participants must currently be on a stable (for at least 4 weeks) and adequate (according to the MGH ATRQ) dose of ongoing Selective serotonin reuptake inhibitor (SSRI) or Serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant therapy, of which total duration must be at least 8 weeks. Participants may also have a history of intolerance to at least 2 antidepressant medications. These patients with the intolerance history will not be required to be currently taking an antidepressant medication.
5. Meet the threshold on the total Hamilton Depression 17-item Scale (HAMD17) score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0).
6. In good general health, as ascertained by medical history, physical examination (PE) (including measurement of supine and standing vital signs), clinical laboratory evaluations, and 12-lead electrocardiogram (ECG).
7. If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:

   1. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or
   2. Childbearing potential, and meets the following criteria:

   i. Childbearing potential, including women using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent.

   ii.Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at randomization prior to receiving study treatment.

   iii.Willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence. The form of birth control will be documented at screening and baseline.
8. Body mass index between 18-35kg/m2.
9. Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive behavioral, insight-oriented, et al) and frequency (e.g., weekly or monthly) of the therapy has been stable for at least three months prior to screening and if the type and frequency of the therapy is expected to remain stable during the course of the subject's participation in the study.
10. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study.

Exclusion Criteria:

A potential participant will NOT be eligible for participation in this study if any of the following criteria are met:

1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
2. Female that is pregnant or breastfeeding.
3. Female with a positive pregnancy test at screening or baseline.
4. Total HAMD score of \<20 at the screen or baseline visits.

6. Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR™), with the exception of nicotine dependence, at screening or within six months prior to screening.

7. Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more).

8. History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes.

9. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within five years of screening.

10. Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant to their MDD at any time within six months prior to screening.

11. Considered at significant risk for suicide during the course of the study according to any of the following criteria:

12. In the judgment of the investigator, the subject is at significant risk for suicidal behavior during the course of his/her participation in the study.

13. Has dementia, delirium, amnestic, or any other cognitive disorder.

14. Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results.

15. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.

16. Known history or current episode of:

a. QTcF (a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle-Fridericia-corrected) ≥450 msec at screening (Visit 1) or randomization b. Syncopal event within the past year. c. Congestive heart failure (CHF) New York Heart Association Criteria \>Stage 2 d. Angina pectoris e. Heart rate \<50 or \>105 beats per minute at screening or randomization

17. Chronic lung disease.

18. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system (CNS), or a history of significant head trauma within the past two years.

19. Presents with any of the following lab abnormalities w/in the past 6 months:

1. Thyroid stimulating hormone (TSH) outside of the normal limits and clinically significant as determined by the investigator. Free thyroxine (T4) levels may be measured if TSH level is high. Subject will be excluded if T4 level is clinically significant.
2. Any other clinically significant abnormal laboratory result at the time of the screening exam.

   20. History of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than six months prior to screening.(Subjects on a stable dosage of thyroid replacement medication for at least six months or more prior to screening are eligible for enrollment.)

   21. History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening.

   22. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.

   23. History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.

   24. Chronic use of opiates.
B: Inclusion Criteria:

* Participants must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for major depressive disorder
* Participants must have current suicidal ideation with intent
* In the Investigator's opinion, participant must be in need of acute psychiatric hospitalization due to imminent risk of suicide
* Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than or equal to (\>=) 22 predose on Day 1
* As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 5 days after randomization (that is, through Day 5), and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)

Exclusion Criteria:

* Participant has a current clinical diagnosis of bipolar or related disorders, intellectual disability, or cluster b personality disorder (example, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder)
* Participant meets DSM-IV criteria for borderline personality disorder, based on clinical interview
* Participant has a current or prior diagnosis of a psychotic disorder, major depressive disorder (MDD) with psychosis, or obsessive compulsive disorder
* Participant with a history or current signs and symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances
* Participant has uncontrolled hypertension (systolic blood pressure greater than \[\>\] 160 millimeter of mercury \[mmHg\] or diastolic blood pressure \> 90 mmHg) despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment at Screening; or any past history of hypertensive crisis
C: INCLUSION CRITERIA:

* Unipolar depression with current major depressive episode (MDE). Participants may be psychiatric medication-free, or if on psychiatric medication, not responding adequately given current MDE with suicidal ideation (See 2).
* Moderate to severe suicidal ideation
* 18-65 years old
* Participants must agree to a voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI)for the infusion(s), for a brief stay, or longer if clinically necessary.
* Pre-menopausal female participants of child-bearing potential must be willing to use an acceptable form of birth control during study participation such as condoms, diaphragm, or oral contraceptive pills.
* Able to provide informed consent
* Participants 61-65 years old must score a 25 or higher on the Mini-Mental State Examination (MMSE) at screening.

EXCLUSION CRITERIA:

* Unstable medical condition or neurological illness, including baseline hypertension (BP\>140/90) or significant history of cardiovascular illness.
* Significant ECG abnormality
* Pregnant or lactating
* Diagnosis of bipolar disorder or psychotic disorder
* Contraindication to any study treatment.
* Inadequate understanding of English.
* Prior ineffective trial of or adverse reaction to Ketamine or Midazolam.
* Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3 days pre-infusion.
* A diagnosis of sleep apnea.
D: Inclusion Criteria:

* Patients with a diagnosis of Major Depressive Disorder, currently depressed without psychotic features
* Females must be of non-childbearing potential.

Exclusion Criteria:

* Treatment with Clozapine or ECT within 3 months prior to study
* Current or past history of psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV

Answer: B