Ketamine Versus Electroconvulsive Therapy in Depression

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

While there are effective treatments for depression available, some patients do not see results with these options. Often, these patients are referred to electroconvulsive therapy (ECT) which has drawbacks such as adverse side effects, cost, and limited access. Recent research shows that intravenous ketamine may be an alternative option for these patients due to its rapid antidepressant effect sustained with multiple treatments.

This study will recruit 240 participants from the ECT waiting list at the five participating hospitals, and randomize them to either the ketamine or ECT treatment arm. Participants in the ketamine treatment arm will receive 0.5mg/kg ketamine intravenously (IV) over 40 minutes as described in the study schedule. Participants in the ECT treatment arm will receive ECT as described in the study schedule and as decided by their treating physician. Throughout the study, clinical, neuroimaging, molecular, and cognitive assessments will be conducted.

The aim of this study is to show that compared to ECT, ketamine treatment produces faster results, has less side effects, requires less or shorter hospitalizations, and is less expensive. The measures collected throughout the study (clinician scales, self-reports, blood samples, and neuroimaging) may help with predicting if future patients will respond to ECT or ketamine. This could lead to faster, more effective treatment for patient with depression.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Ottawa
• Collaborators: McGill University; Queen's University; Sunnybrook Health Sciences Centre; University Health Network, Toronto
• Treatments: Ketamine

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:

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 5.2x1012/L in females and under 4.4 or over 5.7x1012/L in males

• MCV under 80 or over 100 fL

• WBC under 4 or over 10x109/L

• Neutrophil over 0.7x109/L

• Lymphocyte under 1.0 or over 4.0x109/L

• Monocyte under 0.1 or over 1.0x109/L

• Eosinophil over 0.45x109/L

• Basophils over 0.10x109/L

• Platelets under 130 or over 400x109/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).