Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Investigation of the Antidepressant Effects of the Selective NR2B Antagonist MK-0657 in Major Depression
Brief Summary: Purpose : This study will determine whether MK-0657, a selective NR2B Antagonist, can quickly improve symptoms of depressed mood, psychomotor retardation, poor motivation and reduced enjoyment of things in patients with major depression.

MK-0657 decreases the activity of a brain receptor called NMDA, which the chemical glutamate binds to, possibly inducing a rapid antidepressant response. People between 18 and 55 years of age who have major depression of at least 4 weeks' duration and have not been helped by two antidepressants approved for major depression may be eligible for this study. Women who are able to have children are excluded. Participants are admitted to the NIH Clinical Center for two study phases, as follows. Phase I (1 to 2 weeks): Patients are tapered off their current medications. Phase II (7 weeks): Patients are randomly assigned to take either MK-0657 or placebo (look-alike capsules with no active ingredient) by mouth for 12 days. At some point during the second part this phase, patients who had been taking MK-0657 are switched over to placebo and those who had been taking placebo are switched to MK-0657. Participants undergo the following procedures during the study:Physical examination twice (at the beginning and at the end of the study) Electrocardiogram (ECG) four times Blood tests about six times Rating scales up to 28 times to assess the effects of MK-0657 on mood and thinking Blood pressure measurements three times a day.

Study examines the effectiveness of a new medication, targeting a system called glutamate, will improve depression when compared with placebo.


Options:
A: INCLUSION CRITERIA:

1. Male or female (not of reproductive potential, unable to conceive) subjects, 18 to 55 years of age. A female patient not of reproductive potential is defined as one who: a) has reached menopause with: i) no menses for the past 3 or more years OR ii) no menses for greater than 1 year but less than 3 years with confirmation of FSH levels elevated into the postmenopausal range; or b) has undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation.
2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
3. Subjects must fulfill DSM-IV criteria for Major Depression (296.3) without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P.
4. Subjects must have an initial score of at least 22 on the MADRS at screen and at baseline of study phase II.
5. Current or past history of lack of response to two adequate antidepressant trials (may be from the same chemical class) operationally defined using the Antidepressant Treatment History Form (ATHF). If subjects have only failed to respond to one adequate antidepressant trial by history, they will be permitted to receive a prospective trial of a standard antidepressant. Subjects who fail to respond to this prospective trial will meet criteria for treatment-resistance and be eligible to randomize. Subjects responding to the prospective trial will be ineligible to randomize. (A CORE representative will be present when the subject is informed as to the decision to randomize or not).
6. Current major depressive episode of at least 4 weeks duration.

EXCLUSION CRITERIA:

1. Current or past history of bipolar disorder, psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV.
2. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (including for nicotine and caffeine) within the preceding 3 months.
3. Subjects with a diagnosis of Obsessive Compulsive Disorder or Posttraumatic Stress Disorder as defined in the DSM-IV.
4. Subjects with a diagnosis of Borderline or Antisocial Personality disorder. Other Axis II disorders do not qualify one for exclusion from the study.
5. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
6. Patient has a history of any cardiovascular disease, including myocardial infarction, cardiac arrhythmias or conduction abnormalities, cerebrovascular accident, transient ischemic attack (TIA), or peripheral vascular disease.
7. Patient has systolic blood pressure of less than 90 mm Hg or greater than 135 mm Hg at the screen visit or has orthostatic hypotension at the screen visit (greater than or equal to 20 mm Hg decline in systolic blood pressure compared with previous supine systolic blood pressure plus orthostatic symptoms within 3 minutes after standing).
8. Clinically significant abnormal laboratory test or electrocardiogram.
9. Subjects with uncorrected hypothyroidism or hyperthyroidism.
10. Subjects with one or more seizures without a clear and resolved etiology.
11. Previous lack of antidepressant response to ketamine or hypersensitivity to ketamine or amantadine.
12. Treatment with fluoxetine within 5 weeks prior to study phase I.
13. Treatment with any other concomitant medication not allowed 7 days (14 days for MAOIs) prior to study phase II.
14. Treatment with clozapine or ECT within 2 months prior to study phase II.
15. MADRS greater than 4 on item 10 (suicidal ideation).

No structured psychotherapy will be permitted during the study.
B: Inclusion Criteria:

1. Gender: female or male,
2. Age: 18 - 65 years old, inclusive, on the day of Screening,
3. Participant must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for depressive episode in Bipolar Disorder (BD) type I or II, without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI),
4. Participant must have in Montgomery-Asberg Depression Rating Scale (MADRS) total score of \>= 24 at Screening and predose on Day 1,
5. Participant is treatment resistant in the current episode of depression, defined as having an inadequate response to at least 2 adequate mood stabilizing treatment regimens administered for the sufficient duration and dose and administered in the current episode of depression,
6. Participant in the last mood stabilizing treatment regimen is to be administered at least one of the medication listed in the protocol,
7. Participant's last mood stabilizing treatment regimen is to be without antidepressant drugs from the class: SSRI, SNRI, TCA, MAOI or NaSSA,
8. Participant must be on stable mood stabilizing treatment regimen (listed in the protocol), remain non-responsive to it and continue the treatment from Screening to at least the duration of the double-blind treatment phase,
9. Participant's other drugs taken as a standard treatment for bipolar disorder, but not for depressive episode treatment, are to be allowed and may be continued through the study and it's administration is up to Investigator discretion,
10. Participant agrees to be hospitalized voluntarily for a period of 12 h before first administration and until the end of treatment phase on Day 14,
11. Participant must be medically stable on the basis of clinical laboratory tests, physical examination, vital signs, 12-lead ECG,
12. Participant agrees to blood sample collection for DNA analysis,
13. Participant of childbearing potential willing to use acceptable forms of contraception.

Exclusion Criteria:

1. Participant has a current DSM-5 diagnosis, according to MINI, of any other than BD disorder,
2. Participant has a BD with a rapid-cycling course (≥ 4 episodes per year),
3. Participant has in Young Mania Rating Scale (YMRS) total score of greater than 12 at Screening and every other assessment,
4. Participant has suicidal ideation in MADRS 'suicidal thoughts' subscale score greater or equal to 2 and/or in C-SSRS score greater or equal to 4 at Screening and/or has a history of suicidal thoughts within 6 months prior to Screening and/or history of suicidal attempt within 1 year prior to Screening,
5. Participant has a history or current signs and symptoms of chronic obstructive pulmonary disease (COPD), asthma, liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, neurologic, rheumatologic or metabolic disturbances that are uncontrolled with medication change during last three months before Screening and/or that could influence the present general health condition at the Investigator's discretion,
6. Participant has uncontrolled hypertension,
7. Upper respiratory tract and/or chest infection and/or inflammation within 2 weeks preceding the first administration and during the treatment phase,
8. Participant took part in other clinical trial within 90 days preceding the Screening,
9. Known allergy or hypersensitivity, intolerance or contraindication to Esketamine/ketamine or its derivatives and/or to any study product excipients,
10. Blood drawn within 30 days prior to inclusion to the study,
11. History of drug, alcohol, chemical, sedatives or sleeping medications abuse or dependence (except nicotine or caffeine) within 2 years prior to Screening,
12. Lifetime abuse or dependence on ketamine or phencyclidine,
13. Positive results from pregnancy test for female participants,
14. Lactation in female participants,
15. Positive drug screen (except benzodiazepines evaluation during follow-up) or alcohol breath test.
C: Inclusion Criteria:

* diagnosis of major depressive disorder consistent with DSM-IV-TR
* current episode greater than 8 weeks in duration
* Hamilton Depression score \>/- 21
* less than 25% reduction in depression during current episode assessed by ATRQ

Exclusion Criteria:

* Axis diagnosis of other psychiatric disorders
* Experiencing hallucinations, delusions, other psychotic symptomatology
* ECT during current episode
D: Inclusion Criteria:

* clinical laboratory values \< 2x the upper limit of normal
* ability to understand the requirements of the study and provide informed consent

Exclusion Criteria:

* alcohol abuse
* abuse of illicit substances
* current smoker
* currently taking prescription medications (other than for birth control)
* history of allergy to NMDA receptor ligands
* received another investigational drug within 30 days
* psychiatric disease

Answer: A