Ketamine in the Treatment of Depression
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Ketamine; Saline; Magnetic Resonance Imaging (MRI)
Intervention description: Single dose of 0.1, 0.2, 0.3, 0.4 or 0.5 mg/kg of ketamine given intravenously over 40 minutes.; Single infusion of saline given intravenously over 40 minutes.; 90-minute scan during the 40-minute infusion.
Intervention MeSH terms: Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Ketamine; Major Depressive Disorder; Treatment; Depression

Summary:

      Depressed patients will be offered experimental treatment with a new, potentially fast-acting
      antidepressant called ketamine while being scanned by magnetic resonance imaging (MRI) to
      measure the chemical effect of the drug. Ketamine will be given in a dose of 0.0 (placebo),
      0.1, 0.2, 0.3, 0.4, or 0.5 mg/kg. If a patient does not respond to ketamine after the first
      infusion, it may be because s/he received ketamine placebo or the dose of ketamine was too
      low. In that case, an optional second scan and infusion of active ketamine (0.5 mg/kg) will
      be offered. This second scan will occur no later than weeks after the first scan/infusion (as
      scheduling permits). There is no guarantee that the patient will respond to the second
      ketamine infusion. Patients enrolled in the study are eligible for up to 6 months treatment
      with their study psychiatrist after the ketamine infusion(s).

      Healthy Volunteers: Healthy controls will receive an infusion of ketamine at a single dose
      (0.5 mg/kg). Volunteers will only receive one MRI scan and infusion.
    

Eligibility criteria:

        Patient Inclusion Criteria:

          -  Patient suffering from a major depressive episode (MDE) as part of an major depressive
             disorder (MDD). Patients may be psychiatric medication-free or, if on psychiatric
             medications, not responding adequately.

          -  Patient scores at least 22 on the Montgomery-Åsberg Depression Rating Scale (MADRS)

          -  Age range 18-65 years

          -  Patient is off all psychotropic and other types of drugs likely to interact with
             glutamate for at least 14 days before starting the study with an exception of chloral
             hydrate or short acting benzodiazepines for distressing anxiety or insomnia

          -  Subject is likely to be able to tolerate a medication washout

          -  Female subjects of child-bearing potential must be using an acceptable method of birth
             control throughout the study.

          -  Must be enrolled in New York Psychiatric Institute (NYSPI) study #4815

        Patient Exclusion Criteria:

          -  Lifetime history of schizophrenia,schizoaffective illness, Bipolar Disorder, or
             psychosis.

          -  First-degree relative with schizophrenia, schizoaffective disorder, or bipolar
             disorder if the subject is less than 33 years old

          -  Significant uncontrolled physical illness particularly if it may affect the brain or
             glutamatergic system including blood dyscrasias lymphomas, hypersplenism,
             endocrinopathies, renal failure or severe chronic obstructive lung disease, autonomic
             neuropathies and active malignancy.

          -  Subjects will be excluded for baseline hypertension (BP>140/90) or significant history
             of cardiovascular illness

          -  Significant ECG abnormalities

          -  Lacks capacity to consent

          -  Patients who are actively suicidal as defined by a suicidal ideation score of 4 or 5
             or suicidal behavior score > 0 on the Columbia Suicide Severity Rating Scale (C-SSRS)
             at in-person screening interview will be excluded from participating as outpatients
             and may only participate as inpatients if the independent inpatient treatment team
             agrees with the plan to enroll the patient.

          -  Electroconvulsive therapy (ECT) within the last 3 months for this episode

          -  Pregnancy or plans to conceive during the course of study participation

          -  Heart pacemaker, body implant or other metal in body

          -  A neurological disease or prior head trauma with evidence of cognitive impairment.

          -  Patients who are responding satisfactorily to antidepressant medications because they
             will not be washed-out for purposes of this study

          -  Claustrophobia sufficient to preclude MRI

          -  Irremovable medicinal patch

          -  Prior ineffective trial of, or adverse effect to, ketamine

          -  Subjects judged unlikely to be able to tolerate a psychoactive medication washout of
             14 days

          -  Inadequate understanding of English

          -  IV drug use or history of ketamine use as a recreational drug ≥ 2 times or an adverse
             reaction to ketamine

        Control Inclusion Criteria:

          -  Age 18-65

          -  Physically healthy

          -  Absence of an Axis I diagnosis (specific phobia acceptable). Absence of Borderline
             Personality Disorder and Antisocial Personality Disorder.

          -  Not on any medications known to affect glutamatergic functioning

          -  Female subjects of child-bearing potential must be using an acceptable method of birth
             control throughout the study.

          -  Must be enrolled in NYSPI protocol #4815

        Control Exclusion Criteria:

          -  First degree relative with MDD; first degree relative with Schizophrenia,
             Schizoaffective Disorder, Bipolar disorder, if the subject is less than 33 years old,
             and therefore still at significant risk

          -  Significant active physical illness particularly if it may affect the brain or
             glutamatergic system including blood dyscrasias lymphomas, hypersplenism,
             endocrinopathies, renal failure or severe chronic obstructive lung disease,autonomic
             neuropathies and active malignancy.

          -  Subjects will be excluded for baseline hypertension (BP>140/90) or significant history
             of cardiovascular illness.

          -  Significant ECG abnormalities

          -  Pregnancy or plans to conceive during the course of study participation

          -  Heart pacemaker, body implant or other metal in body

          -  A neurological disease or prior head trauma with evidence of cognitive impairment.

          -  Claustrophobia sufficient to preclude MRI

          -  Irremovable Medicinal patch

          -  Inadequate understanding of English

          -  Lifetime history of substance dependence,current or past substance abuse will be
             excluded; IV drug use or history of ketamine use as a recreational drug ≥ 2 times or
             an adverse reaction to ketamine will be excluded.