Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboTerminated

Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy

Double-blind, randomised, parallel-group RCT (n=24 adolescents) comparing six 0.5 mg/kg IV ketamine infusions (2/week for 3 weeks) versus six midazolam infusions; primary outcome CDRS at Day 18; 6-month open extension offers ketamine to midazolam non-responders.

Target Enrollment
24 participants
Study Type
Phase II/III interventional
Design
Randomized, double Blind

Detailed Description

Phase 1 is a 3-week double-blind parallel trial comparing six ketamine infusions (0.5 mg/kg over 40 minutes) with six midazolam infusions in 24 adolescents with treatment-resistant major depressive disorder; primary endpoint is CDRS at Day 18.

Phase 2 is a 6-month open extension offering ketamine (six infusions over 3 weeks) to midazolam non-responders; all participants are followed weekly for 6 months with monthly neurocognitive assessments and monitoring for time to relapse and safety outcomes.

Study Protocol

Preparation

sessions

Dosing

6 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

IV ketamine infusions (0.5 mg/kg) given twice weekly for 3 weeks (6 infusions).

Interventions

  • Ketamine0.5 mg/kg
    via IV• two per week for 3 weeks• 6 doses total

    0.5 mg/kg IV infusion over 40 minutes; max single dose 40 mg (≈80 kg).

Midazolam

active comparator

Active control midazolam infusions to maintain blinding.

Interventions

  • Placebo0.045 mg/kg
    via IV• two per week for 3 weeks• 6 doses total

    Midazolam 0.045 mg/kg (max 3.6 mg per infusion) IV; used as active control.

Participants

Ages
13 – 17
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Male or female ages 13-17 years
  • 2. Meet DSM-5 (Diagnostic and Statistical Manual 5) criteria for Major Depressive Disorder by structured interview (MINI-KID)
  • 3. Children's Depression Rating Scale, Revised CDRS score ≥40 at screening
  • 4. Failure to achieve remission with at least 2 antidepressant trials (e.g. SSRI, SNRI or TCA), meaning at least 6 weeks at therapeutic dosing, including at least 4 weeks of stable dosing
  • 5. Stable psychiatric medications and doses for the month prior to enrollment. Subjects may continue to engage in any ongoing psychotherapy.
  • 6. Medically and neurologically healthy on the basis of physical examination and medical history.
  • 7. Parents able to provide written informed consent and adolescents must additionally provide assent.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. History of psychotic disorder, manic episode, autism spectrum disorder diagnosed by MINI-KID
  • 2. History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology.
  • 3. Intellectual disability (IQ<70) per medical history
  • 4. Pregnancy (urine pregnancy tests on the day of infusions for menstruating girls) or lactation
  • 5. Prior treatment with ketamine for depression or prior recreational use of ketamine.
  • 6. Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.

Study Details

Locations

Yale Child Study Center — New Haven, Connecticut, United States

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