Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboUnknown status

Evaluation of Schemes of Administration of Intravenous Ketamine in Depression

Double-blind randomised Phase III trial (n=30) testing eight IV ketamine infusions (0.5 mg/kg over 40 minutes, twice weekly) versus saline in adults 18–65 with treatment-resistant major depressive disorder, assessing clinical response and pgACC glutamate/GABA changes by H1-MRS.

Target Enrollment
30 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomised, double-blind, parallel-group trial of IV ketamine (0.5 mg/kg) given twice weekly for 4 weeks (8 infusions) versus saline placebo in adults with treatment-resistant depression.

Primary clinical outcomes assess response by HDRS/MADRS in the first 24 hours and up to 12 weeks; mechanistic outcomes evaluate glutamate and GABA changes in the pgACC using H1-MRS at baseline, during infusion, 24 hours and 1 week after the final infusion.

Blinded phase is followed by an open-label extension where placebo recipients receive ketamine; safety monitoring includes vitals, adverse events and clinical assessments with 12-week follow-up.

Study Protocol

Preparation

sessions

Dosing

8 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

IV ketamine 0.5 mg/kg over 40 minutes, twice weekly for 4 weeks (8 infusions).

Interventions

  • Ketamine0.5 mg/kg
    via IV• twice weekly• 8 doses total

    Diluted in 100 mL saline 0.9% over 40 minutes; brands: Ketalar/Anesket

Placebo

inactive

Saline 0.9% IV over 40 minutes, twice weekly; blinded placebo with later open-label ketamine crossover.

Interventions

  • Placebo
    via IV• twice weekly• 8 doses total

    Saline 0.9% over 40 minutes; blinded phase then open-label crossover to ketamine for placebo arm

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Age: 18-65 years
  • 2. MDD diagnosis as provided by DSM-5 criteria
  • 3. TRD as defined by failure to achieve response to two consecutive antidepressant therapies at an adequate dose and duration
  • 4. Patients approving inclusion by signing the informed consent

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Comorbidity with other mental and neurological disorders (except generalized anxiety disorder)
  • 2. Substance use disorders at least 3 months prior to enrollment
  • 3. Evidence of structural abnormalities in basal MRI
  • 4. Pregnancy or lactation
  • 5. Hypersensitivity to ketamine
  • 6. Cardiac failure
  • 7. Personal history of psychosis
  • 8. First-degree relatives with history of psychosis
  • 9. Uncontrolled close-angle glaucoma
  • 10. Neurological disease (present)
  • 11. Uncontrolled Hypertension
  • 12. Contraindications for the realization of H1-MRS.

Study Details

Locations

Instituto Nacional de Neurología y Neurocirugía (National Institute of Neurology and Neurosurgery) — Mexico City, Tlalpan, Mexico

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