Please select the eligibility criteria that correspond to the clinical trial below.
Title: Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression
Brief Summary: This study is designed to compare the effectiveness of two medications, Ketamine and Midazolam, for rapidly relieving suicidal thoughts in people suffering from depression.

The first drug, Ketamine, is an experimental antidepressant that early studies have shown may quickly reduce suicidal thoughts, but we are not sure how well it may work. Midazolam, the comparison drug, is not thought to reduce depression or suicidal thoughts.


Options:
A: 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.
B: Inclusion Criteria:

* Male or female, 18-70 years old.
* Able to read, understand, and provide written, dated informed consent prior to screening.
* 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.
* Has a history of TRD during the current MDE.
* Meet the threshold on the total MADRS score of greater than or equal to 20 at both screening and baseline visits (Day -7/-28 and Day 0), as confirmed by the remote centralized MGH CTNI rater between the screen visit and the baseline visit.
* In good general health
* For female participants, status of non-childbearing potential or use of an acceptable form of birth control
* Body mass index between 18-35 kg/m2
* Concurrent psychotherapy will be allowed if the type and frequency of the therapy has been stable for at least three months prior to screening and is expected to remain stable during participation in the study
* Concurrent hypnotic therapy 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:

* Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study
* Female that is pregnant or breastfeeding
* Female with a positive pregnancy test at screening or baseline
* History during the current MDE of failure to achieve a satisfactory response to \>7 treatment courses of a therapeutic dose of an antidepressant therapy of at least 8 weeks duration during the current episode
* Total MADRS score of \<20 at the screen or baseline visits, or as assessed by the remote, independent MGH CTNI rater and reported to the site
* Current diagnosis of a Substance Use Disorder (Abuse or Dependence) with the exception of nicotine dependence, at screening or within 6 months prior to screening
* Current Axis I disorder that is the principal focus of treatment and MDD the secondary focus of treatment for the past 6 months or more
* History of bipolar disorder, schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes
* History of eating disorders within five years of screening
* Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant at any time within 6 months prior to screening
* Subject is considered at significant risk for suicidal behavior during the course of their participation in the study
* Has failed to respond to electroconvulsive therapy (ECT) during the current depressive episode
* Has received vagus nerve stimulation (VNS) at any time prior to screening
* Has dementia, delirium, amnestic, or any other cognitive disorder
* Has a clinically significant abnormality on the screening physical examination
* Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation
* Current episode of:

  1. Hypertension, Stage 1 as defined by a systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90 mmHg at screening on two of three measurements (standing and supine) at least 15 minutes apart.
  2. Hypertension, Stage 1 as defined by a systolic blood pressure ≥155 mmHg or diastolic blood pressure ≥99 mmHg at the Baseline Visit (Visit 1) within 1.5 hours prior to randomization on two of three measurements (standing and supine) at least 15 minutes apart.
  3. Recent myocardial infarction (within one year) or a history of myocardial infarction.
  4. Syncopal event within the past year.
  5. Congestive heart failure (CHF) New York Heart Association Criteria \>Stage 2
  6. Angina pectoris.
  7. Heart rate \<50 or \>105 beats per minute at screening or randomization (Baseline Visit).
  8. QTcF (Fridericia-corrected) ≥450 msec at screening or randomization (Baseline Visit).
* Current history of hypertension, or on antihypertensives for the purpose of lowering blood pressure, who have either had an increase in antihypertensive dose or increase in the number of antihypertensive drugs used to treat hypertension over the last 2 months.
* Chronic lung disease excluding asthma.
* Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system disorder, epilepsy, mental retardation, or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system, or a history of significant head trauma within the past 2 years
* Presents with any of the following lab abnormalities:

  1. Thyroid stimulating hormone 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. Patients with diabetes mellitus fulfilling any of the following criteria:

  i. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) \>8.5% at screening ii. Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus related illness in the past 12 weeks iii. Not under physician care for diabetes mellitus iv. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 weeks.

  c. Any other clinically significant abnormal laboratory result (as determined after evaluation by study investigator and MGH CTNI medical monitor) at the time of the screening exam.
* History of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than 2 months prior to screening. (Subjects on a stable dosage of thyroid replacement medication for at least 2 months or more prior to screening are eligible for enrollment.)
* History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening
* 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
* History of positive screening urine test for drugs of abuse at screening
* Patients with exclusionary laboratory values, or requiring treatment with exclusionary concomitant medications
* Patients on exclusionary concomitant psychotropic medications, the half-life of which would not allow sufficient time for patients to have been free of the medication post-taper for five half-lives within the maximum screening period (28 days).
* Patient who have participated in studies of ketamine or AZD6765 or other NMDA receptor antagonists for depression and received active treatment.
* Patients with narrow angle glaucoma
* Patients with a lifetime history of PCP/Ketamine drug use
* Liver Function Tests higher than 2.5 times upper limit of normal
C: Inclusion Criteria:

* DSM-IV diagnosis of major depression .
* HAMD scale score of ≥20 despite at least two adequate antidepressant treatment trials during the current episode.

Exclusion Criteria:

* Underwent ECT treatment during the 3 months preceding the study.
* Change in psychotropic medications doses during the 3 weeks preceding the study.
* Concurrent unstable medical or neurological illness.
* Patients are judged to be potentially violent towards themselves or others, or have a history of drug/alcohol abuse.
D: 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

Answer: A