Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboActive not yet recruiting

Study of Ketamine for Youth Depression

Randomised, parallel Phase III trial (n=140) of low-dose subcutaneous ketamine (starting 0.6 mg/kg, titrated up to 0.9 mg/kg; weekly ×4) versus low-dose midazolam in 16–25-year-olds with moderate-to-severe major depressive disorder.

Target Enrollment
140 participants
Study Type
Phase III interventional
Design
Randomized, single Blind

Detailed Description

Randomised, parallel, blinded Phase III study comparing weekly subcutaneous ketamine to low-dose midazolam in young people (16–25 years) with moderate-to-severe major depressive disorder; total sample size 140.

Intervention: ketamine starting at 0.6 mg/kg subcutaneously once weekly for four weeks with escalation to 0.9 mg/kg for inadequate response and reduction to 0.5 mg/kg for intolerance; comparator: midazolam 0.03 mg/kg with analogous titration (max 0.045 mg/kg, min 0.025 mg/kg). Acute observation: 4 hours after first dosing and 2 hours after subsequent doses.

Primary outcome is change in MADRS at 4 weeks versus baseline; additional follow-ups at Week 8 (Day 56) and Week 26 (Day 182) assess sustained change.

Study Protocol

Preparation

sessions

Dosing

4 sessions
240 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Low-dose subcutaneous ketamine with dose escalation for inadequate response and dose reduction for intolerance.

Interventions

  • Ketamine0.6 - 0.9 mg/kg
    via Other• weekly• 4 doses total

    Subcutaneous injection; starting 0.6 mg/kg, escalation up to 0.9 mg/kg for inadequate response; reduction down to 0.5 mg/kg if not tolerated; initial observation 4 h, subsequent 2 h.

Midazolam

active comparator

Low-dose subcutaneous midazolam active comparator with titration rules matching ketamine schedule.

Interventions

  • Placebo0.03 - 0.045 mg/kg
    via Other• weekly• 4 doses total

    Subcutaneous injection; starting 0.03 mg/kg, escalation to 0.045 mg/kg for inadequate response, reduction to 0.025 mg/kg if not tolerated.

Participants

Ages
16 – 25
Sexes
Male & Female

Inclusion Criteria

  • Age 16–25 years inclusive at the time of providing informed consent.
  • Current MDD as assessed using the Structured Clinical Interview for DSM-5 (SCID-5).
  • MADRS score greater than or equal to 22 within 7 days of the first treatment visit.
  • Treatment with either a stable dose of an antidepressant or no antidepressant medication for greater than or equal to 2 weeks.
  • Ability to provide written informed consent, including adequate intellectual capacity and fluency in the English language.

Exclusion Criteria

  • Severe disturbance such that the young person would be unable to comply with informed consent or the study protocol, as determined by the trial doctor.
  • History of psychosis or bipolar disorder (assessed with SCID-5).
  • Any unstable medical or neurologic condition, or medical or pharmaceutical contraindication to ketamine or midazolam use.
  • Any history of a ketamine use disorder of any severity, or presence of a substance use disorder of at least moderate severity (DSM-5) within the preceding 6 months.
  • Females who are pregnant or currently breastfeeding, or who are not using effective contraception.
  • Participation in any other clinical intervention trial from SKY-D baseline to the Week 8 follow-up.

Study Details

Locations

Unknown facility — Australia

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