Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Doubly-Randomized, Placebo-Controlled Study of Intranasal Esketamine in an Adaptive Treatment Protocol to Assess Safety and Efficacy in Treatment-Resistant Depression (SYNAPSE)
Brief Summary: The purpose of this study is to assess the efficacy and dose response of intranasal esketamine (Panel A: 28 mg, 56 mg, and 84 mg and Panel B: 14 mg and 56 mg) compared with placebo in improving depressive symptoms in participants with treatment-resistant depression (TRD).


Options:
A: Inclusion Criteria:

* Documented clinical diagnosis meeting criteria from the DSM-IV by structured clinical interview,major depressive disorder, single episode or recurrent
* Outpatient status at screening and at randomisation

Exclusion Criteria:

* A major depression disorder which has a major impact on the subjects current psychiatric status
* Subjects not allowed to use mood stabilizers, antidepressants or other antipsychotic or psychoactive drugs
* Subjects with lifetime history of schizophrenia, bi-polar, psychosis and psychotic depression
B: Inclusion Criteria:

* Diagnosis of Depression
* Inadequate response to an adequate course of antidepressants

Exclusion Criteria:

* Psychiatric disorder other than depression
* Pregnancy or lactation
* Current diagnosis of cancer
C: Inclusion Criteria:

--Participant must meet Diagnostic and Statistical Manual of Mental Disorders -Fourth Edition -Text Revised (DSM-IV-TR) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment, and confirmed by the Mini International Neuropsychiatric Interview (MINI)-Participant's major depressive episode and treatment response must be deemed "valid" by remote independent raters-Participant must have had an inadequate response to at least 2 antidepressants, at least one of which is in the current episode of depression; the antidepressant treatment response questionnaire (ATRQ) will be used to assess antidepressant treatment response during the current episode; prior medication history will be used to determine antidepressant treatment response in prior episode(s) -Have an Inventory of Depressive Symptoms-Clinician rated, 30-item (IDS-C30) total score \>=34 at Screening and predose at Day 1

Exclusion Criteria:

-Participant has a current DSM-IV-TR diagnosis of bipolar and related disorders, intellectual disability, or cluster b personality disorder (e.g., borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder) -Participant has a current or prior DSM-IV-TR diagnosis of a psychotic disorder, MDD with psychosis, post-traumatic stress disorder (PTSD), or obsessive compulsive disorder (OCD) -Anatomical or medical conditions that may impede delivery or absorption of study medication (e.g., undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; signs and symptoms of rhinitis) -Has an abnormal or deviated nasal septum with any 1 or more of the following symptoms: blockage of 1 or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, and at times has facial pain, headaches, and postnasal drip -Has a history of substance abuse (drug or alcohol) or dependence (except nicotine or caffeine) within the previous 1 year of the screening visit -Participant has known allergies, hypersensitivity, intolerance, or contraindication to esketamine/ketamine or its excipients
D: 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.

Answer: C