Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboTemporarily not available

Ketamine Versus Electroconvulsive Therapy in Depression

Randomised, multi-centre, crossover trial (n=240) comparing IV ketamine (0.5 mg/kg IV over 40 minutes, thrice weekly initial course) versus electroconvulsive therapy (ECT) in patients referred for ECT for severe depression.

Target Enrollment
240 participants
Study Type
Phase III interventional
Design
Randomized, single Blind

Detailed Description

Multi-centre randomised crossover trial enrolling 240 adults referred for ECT to compare efficacy, speed of antidepressant effect, side-effect profile, hospitalisation needs and cost between IV ketamine and ECT.

Participants receive either IV ketamine 0.5 mg/kg infused over 40 minutes thrice weekly for 3–4 weeks (9–12 sessions; upper=12) with a maintenance schedule for responders, or ECT administered per treating physician; responders and non-responders may follow maintenance or crossover pathways as specified.

Outcomes include clinician-rated and self-report measures, neuroimaging, molecular biomarkers and cognitive assessments to evaluate response predictors and comparative effectiveness.

Study Protocol

Preparation

sessions

Dosing

12 sessions
40 min each

Integration

sessions

Study Arms & Interventions

IV ketamine

experimental

Intravenous ketamine arm: repeated 0.5 mg/kg infusions with maintenance for responders.

Interventions

  • Ketamine0.5 mg/kg
    via IV• thrice weekly• 12 doses total

    0.5 mg/kg IV infusion over 40 minutes; initial 3–4 week course (9–12 treatments, upper=12 used), maintenance weekly for one month then biweekly for two months then monthly for three months; may return to biweekly if relapse.

ECT

active comparator

Electroconvulsive therapy as decided by treating physician; thrice weekly initial course with maintenance per clinician.

Interventions

  • Placebo
    via Other• thrice weekly

    Electroconvulsive Therapy (procedure) per treating physician; initial 3–4 week course with maintenance as clinically indicated.

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Provision of written informed consent before initiation of any study-related procedures.
  • 2. Eligible subjects who have consented to standard ECT treatment for their mood disorder and are willing to accept randomization to either ECT or IV ketamine group.
  • 3. Men and women aged between 18 and 70 years, inclusive with a body mass index (BMI) < 35. They must have a Montreal Cognitive Assessment (MOCA) score ≥ 24.
  • 4. Patients meeting criteria for Major Depressive Disorder (MDD) or Bipolar Disorder (BP) without psychotic symptoms according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) currently in a Major Depressive Episode (MDE) as confirmed by the MINI International Neuropsychiatric Interview (MINI).
  • 5. A Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥ 26 at screening and at randomization, with no more than 20% improvement between these two visits.
  • 6. Female subjects of childbearing potential must have a negative urine pregnancy test at enrolment (Visit 1) and be willing to use a reliable method of birth control (i.e., double-barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation) during the study.
  • 7. Abstain from consuming grapefruit juice (a potent 3A4 cytochrome inhibitor) on the day of the ketamine infusions as it may slow down the elimination of ketamine.
  • 8. Be able to understand and comply with the requirements of the study, as judged by the investigator(s).

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Depression secondary to stroke, cancer or other severe medical illnesses.
  • 2. Prior or current substance abuse or dependence (except for caffeine or nicotine dependence) and/or recent history (last 12 months) of current alcohol abuse or dependence, as defined in DSM-5 criteria ("a problematic pattern of using alcohol or another substance that results in impairment in daily life or noticeable distress").
  • 3. A positive toxicology screen for drugs that are not prescribed.
  • 4. Unwilling to maintain current antidepressant regimen.
  • 5. Unwilling or unable to hold benzodiazepines from the evening prior to the infusion of ketamine.
  • 6. Unwilling to discontinue any narcotic for a minimum of 5 drug half-lives prior to injections.
  • 7. Pregnant, lactating, or of childbearing potential and not willing to use an approved method of contraception during the study.
  • 8. Evidence of clinically relevant disease, e.g., uncontrolled hypertension, renal or hepatic impairment, significant coronary artery disease (myocardial infarct within a year prior to initial randomization), cerebrovascular disease, history of cerebrovascular accident, viral hepatitis B or C, acquired immunodeficiency syndrome.
  • 9. A clinical finding that is unstable or that, in the opinion of the investigator(s), would be negatively affected by the study medication or that would affect the study medication (e.g., diabetes mellitus, hypertension, unstable angina).
  • 10. Liver function tests AST and ALT three times the upper normal limit at screening.
  • 11. Uncorrected hypothyroidism or hyperthyroidism. Subjects needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of the medication for 30 days prior to enrolment (Visit 1).
  • 12. Clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator(s). Including:
  • * Sodium under 135 or over 145 mmol/L
  • * Potassium under 3.5 or over 5.0 mmol/L
  • * Chloride under 98 or over 106 mmol/L
  • * ALT under 17 or over 63 U/L
  • * AST under 18 or over 40 U/L
  • * Total bilirubin over 26 mmol/L
  • * GGT under 9 or over 48 U/L
  • * Fasting glucose under 3.3 or over 5.8 mmol/L
  • * BUN under 2.5 or over 8.0 mmol/L
  • * Creatinine under 50 or over 90 mmol/L in females, and under 70 or over 120 mmol/L in males
  • * TSH under 0.4 or over 5.0 mU/L
  • * CBC indicating:
  • * Hemoglobin under 123 or over 157 g/L in females, and under 130 or over 170 g/L in males
  • * Hematocrit under 0.370 or over 0.460 in females, and under 0.380 or over 0.50 in males
  • * RBC under 4.0 or over 5.2x10^12/L in females and under 4.4 or over 5.7x10^12/L in males
  • * MCV under 80 or over 100 fL
  • * WBC under 4 or over 10x10^9/L
  • * Neutrophil over 0.7x10^9/L
  • * Lymphocyte under 1.0 or over 4.0x10^9/L
  • * Monocyte under 0.1 or over 1.0x10^9/L
  • * Eosinophil over 0.45x10^9/L
  • * Basophils over 0.10x10^9/L
  • * Platelets under 130 or over 400x10^9/L
  • 13. ECG results considered clinically significant as determined by the investigator(s), or outside of normal range as per cardiologist analysis.
  • 14. History of seizure disorder, except febrile convulsions.
  • 15. Known history of intolerance or hypersensitivity to ketamine.
  • 16. Any other condition that, in the opinion of the investigator(s), would adversely affect the subject's ability to complete the study or its measure.
  • Note: active suicidal intent in MDD with the absence of psychotic symptoms is not an exclusion criterion.

Study Details

Locations

Providence Care Hospital — Kingston, Ontario, Canada
Royal Ottawa Mental Health Centre — Ottawa, Ontario, Canada
University Health Network — Toronto, Ontario, Canada
Ontario Shores Centre for Mental Health Sciences — Whitby, Ontario, Canada

Your Library