Ketamine Infusion for Adolescent Depression and Anxiety
Condition: Major Depressive Disorder; Anxiety Disorder
MeSH terms: Depression; Depressive Disorder; Anxiety Disorders; Depressive Disorder, Major
Intervention: Ketamine; Midazolam
Intervention description: A single dose of 0.5mg/kg of Ketamine will be administered Intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.; A single dose of 0.045mg/kg of Midazolam will be administered intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.
Intervention MeSH terms: Midazolam; Ketamine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants were randomly assigned the treatment order, with participants receiving a single infusion of either ketamine hydrochloride (0.5 mg/kg) or midazolam (0.045 mg/kg) on Day 1, and the alternate compound 2 weeks later.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Midazolam was chosen as an active placebo in keeping with its similar pharmacokinetic profile and precedent as a reasonable comparator for nonspecific behavioral effects of ketamine
Enrollment: 17.0
Sex: All
Minimum age: 13 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Ketamine; Depression; Major Depressive Disorder; Anxiety; School refusal; Suicide; Generalized Anxiety; Suicidal Ideation

Summary:

      The purpose of this study is to determine the tolerability and short-term efficacy of a
      single ketamine infusion for the treatment of adolescents with 1) medication-refractory major
      depressive disorder (MDD) and/or 2) medication-refractory anxiety disorders (social anxiety
      disorder, panic disorder, generalized anxiety disorder and/or separation anxiety disorder).
    

Eligibility criteria:

        Inclusion:

        MDD Cohort:

          -  Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID)

          -  CDRS-R score >40.

          -  Failure to achieve remission with at least 1 adequate prior antidepressant trial (e.g.
             SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at
             least 4 weeks of stable dosing.

        Anxiety Cohort:

          -  Meet DSM-5 criteria for any of the following anxiety disorders: Social Anxiety
             Disorders, Generalized Anxiety Disorder, Separation Anxiety Disorder and/or Panic
             Disorder by structured interview (MINI-KID)

          -  ADIS Clinical Severity Rating ≥4 (moderately severe) for any of the 4 included anxiety
             disorders

          -  Failure to achieve remission with at least 1 adequate prior anxiolytic medication
             trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing,
             including at least 4 weeks of stable dosing.

          -  Failure to achieve remission with previous CBT or subject declines current CBT therapy

        Both cohorts:

          -  Stable psychiatric medications and doses for the month prior to enrollment. Subjects
             may continue to engage in any ongoing psychotherapy.

          -  Medically and neurologically healthy on the basis of physical examination and medical
             history.

          -  Parents able to provide written informed consent and adolescents must additionally
             provide assent.

        Exclusion:

          -  Current inpatient hospitalization or active suicidal ideation requiring referral for
             inpatient hospitalization for safety.

          -  History of psychotic disorder or manic episode diagnosed by MINI-KID

          -  History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive
             urine toxicology.

          -  Pregnancy (urine pregnancy tests on the day of scans for menstruating girls).

          -  Inability to provide written informed consent according to the Yale Human
             Investigation Committee (HIC) guidelines in English.