Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboWithdrawn

Endogenous Opioid Modulation by Ketamine

Randomized, double-blind, parallel study (withdrawn) testing IV ketamine 0.5 mg/kg infusion over 40 min in adults with treatment-resistant major depressive disorder (actual n=0).

Target Enrollment
Not specified
Study Type
Phase III interventional
Design
Randomized, double Blind

Detailed Description

This randomized, double-blind, parallel study aimed to test whether IV ketamine acutely activates endogenous µ-opioid neurotransmission in adults with treatment-resistant major depressive disorder.

Participants received a single 40-minute infusion of ketamine (0.5 mg/kg total, infused at 0.75 mg/kg/hr) or matching saline; outcomes included PET/neuroimaging measures of µ-opioid system activation and clinical depression ratings.

Study Protocol

Preparation

sessions

Dosing

1 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

IV ketamine infusion (active experimental arm).

Interventions

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

    Infused over 40 minutes at 0.75 mg/kg/hr (total 0.5 mg/kg).

Placebo

inactive

Normal saline infusion (placebo comparator).

Interventions

  • Placebo
    via IV• single dose• 1 doses total

    Normal saline infusion matching ketamine (0.75 mg/kg/hr over 40 minutes).

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Age 18-65
  • DSM-5 major depressive disorder
  • Current moderate-to-severe, treatment-resistant, depressive episode
  • Patient Health Questionnaire (PHQ-9) total score ≥ 10
  • PHQ-9 item score ≥ 2 on "Little interest or pleasure" item
  • PHQ-9 item score ≥ 2 on "Feeling down, depressed, or hopeless" item
  • Medical documentation of depression for at least 2 months
  • Inadequate response to at least one adequate antidepressant medication trial in the current episode

Exclusion Criteria

  • Exclusion Criteria:
  • Current episode duration >5 years
  • Moderate-to-severe DSM-5 substance use disorder (past year)
  • Cognitive disorder (past year)
  • Post-traumatic stress disorder (past year)
  • Obsessive compulsive disorder (past year)
  • Personality disorder (past year)
  • Positive urine drug screen
  • Psychotic symptoms
  • Mania
  • Significant neurologic disorder or injury
  • Breastfeeding or pregnancy
  • Imminent suicide risk
  • Current use of CYP3A4 inhibitors (e.g., ketoconazole or erythromycin)
  • Other unstable psychiatric or medical condition requiring a higher level of care
  • Contraindication to ketamine, MRI, or PET

Study Details

Locations

Huntsman Cancer Institute — Salt Lake City, Utah, United States

Your Library