Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboTerminated

N-methyl-D-aspartate Antagonist (Ketamine) Augmentation of Electroconvulsive Treatment for Severe Major Depression

The investigators propose to assess the efficacy, feasibility, tolerability and safety of N-methyl-D-aspartate antagonist augmentation of ECT using ketamine.

Target Enrollment
17 participants
Study Type
Phase IV interventional
Design
Randomized, double Blind

Detailed Description

Randomized, double-blind, parallel-group Phase IV trial comparing IV ketamine 0.5 mg/kg versus IV saline given before the first three right-unilateral ECT treatments in adults with severe major depressive disorder; primary outcome is time to remission (HAM-D-28).

Secondary aims examine ECT-related cognitive side effects using a neuropsychological battery at baseline, end of acute series and 3-month follow-up; safety and tolerability monitored throughout. Repeated EEG will assess functional connectivity before, during and after ECT.

Planned recruitment was 30 over 24 months; registry record indicates actual count N=17. Conducted at Massachusetts General Hospital, Boston, USA.

Study Protocol

Preparation

sessions

Dosing

3 sessions

Integration

sessions

Study Arms & Interventions

Ketamine + ECT

experimental

IV ketamine (0.5 mg/kg) administered before ECT; right-unilateral ECT at 5-6x seizure threshold three times per week.

Interventions

  • Ketamine0.5 mg/kg
    via IV• before first three ECT treatments• 3 doses total

    Infusion given prior to first three ECT sessions.

  • Compound
    via Other• as per ECT schedule

    Right unilateral ECT at 5-6x seizure threshold; 3x/week.

  • Compound
    via Other

    Routine muscle relaxant given with ECT.

  • Compound
    via Other

    Routine anesthetic agents given with ECT.

Saline + ECT

inactive

IV saline (placebo) administered before ECT; right-unilateral ECT at 5-6x seizure threshold three times per week.

Interventions

  • Placebo
    via IV• before first three ECT treatments• 3 doses total

    IV saline placebo prior to ECT.

  • Compound
    via Other• as per ECT schedule

    Right unilateral ECT at 5-6x seizure threshold; 3x/week.

  • Compound
    via Other

    Routine muscle relaxant given with ECT.

  • Compound
    via Other

    Routine anesthetic agents given with ECT.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. males and females between the ages of 18-65,
  • 2. DSM-IV diagnosis of Major Depressive Disorder (MDD), without psychotic features
  • 3. HAM-D-28 score of 20 or higher
  • 4. requiring ECT treatment as part of their psychiatric care
  • Comorbid anxiety disorders (OCD, Generalized anxiety, panic disorder) will be allowed as long as the clinician administering the SCID believes that they are not the primary diagnosis.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. MDD with a score of <20 on the HAM-D 28,
  • 2. Other DSM-IV primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia
  • 3. any history of psychosis
  • 4. substance use disorder (abuse or dependence with active use within the last 6 months), and any lifetime history of ketamine abuse or dependence
  • 5. organic mental disorders
  • 6. seizure disorder or chronic antiepileptic medications
  • 7. severe or unstable medical illness, including history of closed head injury resulting in loss of consciousness, medical contraindication to anesthesia or to ECT (i.e. recent myocardial infarction, increased intracranial pressure)
  • 8. current treatment with memantine
  • 9. pregnancy, or females of reproductive age who are not using an accepted method of contraception (birth control pill, IUD, combination of barrier methods)
  • 10. known hypersensitivity to ketamine

Study Details

Locations

Massachusetts General Hospital — Boston, Massachusetts, United States

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