Clinical TrialParallelTreatment-Resistant Depression (TRD)KetamineKetamineKetaminePlaceboCompleted

Ketamine for Treatment Resistant Late-Life Depression

Randomized, quadruple-masked Bayesian adaptive dose-finding trial in 33 veterans with late-life treatment-resistant depression, comparing single-infusion IV ketamine 0.1, 0.25, or 0.5 mg/kg with active-control midazolam 0.03 mg/kg.

Ask Blossom about this trial
Target Enrollment
33 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind

Detailed Description

The trial used Bayesian adaptive randomization to identify the best single IV ketamine dose for late-life treatment-resistant depression. The primary endpoint was MADRS treatment response, defined as at least 50% improvement from baseline, at 7 days post-infusion.

Participants were randomized to ketamine 0.1 mg/kg, ketamine 0.25 mg/kg, ketamine 0.5 mg/kg, or midazolam 0.03 mg/kg, each infused over 40 minutes. Midazolam allocations from both adaptive-randomization strata were combined for analysis.

Study Protocol

Preparation

sessions

Dosing

1 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine 0.10 mg/kg

experimental

Single 40-minute IV infusion of ketamine 0.10 mg/kg.

Interventions

  • Ketamine0.1 mg/kg
    via IV• single dose• 1 doses total

    40-minute infusion.

Ketamine 0.25 mg/kg

experimental

Single 40-minute IV infusion of ketamine 0.25 mg/kg.

Interventions

  • Ketamine0.25 mg/kg
    via IV• single dose• 1 doses total

    40-minute infusion.

Ketamine 0.50 mg/kg

experimental

Single 40-minute IV infusion of ketamine 0.50 mg/kg.

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    40-minute infusion.

Midazolam 0.03 mg/kg

active comparator

Single 40-minute IV infusion of midazolam 0.03 mg/kg as active placebo.

Interventions

  • Placebo0.03 mg/kg
    via IV• single dose• 1 doses total

    Active comparator midazolam; Blossom has no dedicated midazolam compound report.

Participants

Ages
55 – ?
Sexes
Male & Female

Inclusion Criteria

  • Veterans at least 55 years old with recurrent or chronic major depressive disorder, treatment resistance to at least two adequate antidepressant trials, and moderate-to-severe depressive symptoms at screening/randomization.

Exclusion Criteria

  • Key exclusions included psychotic disorder, bipolar disorder, recent substance or alcohol use disorder, use of NMDAR or AMPAR medications, and unstable medical or neurological illness.

Study Details

Locations

Michael E. DeBakey VA Medical Center — Houston, Texas, United States

Related Publications

PaywallindividualPrimary

Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial

This randomized Bayesian adaptive dose-finding trial compared single-infusion IV ketamine 0.1, 0.25, and 0.5 mg/kg with active-control midazolam in 33 veterans with late-life treatment-resistant depression. Ketamine 0.5 mg/kg had the strongest day-7 MADRS response signal and better day-28 response durability among day-7 responders.

Published
Journal
Neuropsychopharmacology
Authors
Haile, C. N., Hirsch, L. C.
PaywallindividualSecondary analysis

Neural complexity EEG biomarkers of rapid and post-rapid ketamine effects in late-life treatment-resistant depression: a randomized control trial

In older adults with treatment‑resistant depression, a single sub‑anaesthetic ketamine infusion produced transient increases in EEG neural complexity (Lempel‑Ziv complexity and multiscale entropy) 30 minutes post‑infusion and subsequent reductions in MSE at later post‑rapid timepoints. These time‑varying, system‑wide complexity changes — detectable beyond the gamma oscillation window — suggest neural complexity is a promising non‑linear, amplitude‑independent biomarker of ketamine’s cortical effects, although it did not predict clinical improvement.

Published
Journal
Neuropsychopharmacology
Authors
Murphy, N., Tamman, A. J. F., Lijffijt, M., Amarneh, D., Iqbal, S., Swann, A., Averill, L. A., O'brien, B., Mathew, S. J.