Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboRecruiting

Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine

Early Phase I, randomized, triple-blind, placebo-controlled trial (n=250 MDD; +60 healthy controls) testing a single sub‑anesthetic IV ketamine infusion (0.5 mg/kg) versus saline to assess glutamate stress response, anhedonia, decision-making, and emotion processing.

Target Enrollment
250 participants
Study Type
Phase I interventional
Design
Randomized, triple Blind

Detailed Description

This study evaluates the glutamate stress response and its relation to motivation, valuation, and anhedonia in people with Major Depressive Disorder using multimodal neuroimaging, behavioural tasks, and questionnaires.

MDD participants are randomized to a single IV ketamine infusion (0.5 mg/kg) or saline placebo administered over 40–100 minutes; behavioural and imaging assessments are collected to measure acute and downstream effects.

A separate healthy control cohort (n≈60) completes a behavioural session and one neuroimaging session for baseline comparison and does not receive any intervention.

Study Protocol

Preparation

sessions

Dosing

1 sessions
100 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Single IV ketamine infusion (MDD participants).

Interventions

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

    Infusion over 40–100 minutes via indwelling catheter.

Placebo

inactive

Single IV saline infusion (MDD placebo comparator).

Interventions

  • Placebo
    via IV• single dose• 1 doses total

    Saline infusion over 40–100 minutes via indwelling catheter.

Healthy controls

waitlist

Healthy controls complete behavioural and one neuroimaging session; no intervention.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • MDD Patients:
  • willing and able to give written informed consent
  • men or women, 18-65 years of age
  • primary diagnosis of DSM-V MDD, current, as diagnosed by the SCID-I
  • score of ≥20 on the Beck Depression Inventory
  • off all antidepressant therapy for at least 8 weeks prior to the baseline visit
  • Healthy Controls:
  • willing and able to give written informed consent
  • men or women, 18-65 years of age

Exclusion Criteria

  • Exclusion Criteria:
  • MDD Patients:
  • history of any bipolar disorder or psychotic disorder
  • active psychotic symptoms of any type
  • substance abuse/dependence within 6 months of study entry (as determined by SCID)
  • unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease
  • active suicidal ideation as determined by a score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSR)
  • use of any recreational drugs as confirmed by urine drug screen at the time of scanning
  • pregnancy or lactation
  • use of glucocorticoids at any time during the study
  • Raynaud's disease that may interfere with the cold-pressor
  • contraindications for MRI
  • MMSE score <28
  • elevated blood pressure prior to infusion (systolic >160 or diastolic >100)
  • history of treatment resistance as determined by ATRQ
  • prior adverse reaction to ketamine
  • use of antipsychotic medications
  • use of greater than 2mg daily of lorazepam or similar benzodiazepine
  • Regular smoker as self-reported
  • Healthy Controls:
  • evidence of any psychiatric disorder with exception of specific phobia, and no history of any psychiatric disorder except mild past substance use disorder as diagnosed by the SCID-I
  • history of any substance abuse within the last 6 months
  • use of any recreational drugs as confirmed by urine drug screen at the time of scanning
  • pregnancy or lactation
  • use of glucocorticoids at any time during the study
  • Raynaud's disease that may interfere with the cold-pressor
  • contraindications for MRI
  • MMSE score <28
  • Regular smoker as self-reported

Study Details

Locations

Emory University — Atlanta, Georgia, United States

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