The goal of this study is to compare the effectiveness of two formulations of ketamine - Spravato® and racemic ketamine - in people with treatment-resistant depression (TRD). The main questions it aims to answer are:
* How the two formulations compare in terms of their effectiveness in treating TRD. * How the two formulations compare in their acceptability to patients, safety, effects on patient quality of life and function, and cost effectiveness.
Participants will be randomised to receive either Spravato® or racemic ketamine treatment and asked to complete some questionnaires to assess the effects on mood, treatment acceptability, side effects, quality of life and function, and health economic outcomes.
Adult with treatment-resistant depression (TRD: not responded adequately to at least two different antidepressants of adequate dose and duration) who has a current depressive episode (DSM 5)
Assessed and attested by clinic psychiatrist as appropriate to receive either racemic ketamine or Spravato® ketamine treatment for TRD
MADRS score of ≥20 at study baseline, assessed by certified study rater
Aged ≥18 years
Not able to give informed consent
Any physical or mental condition which, in the opinion of the investigator, could interfere with study participation including outcome assessments
Any treatment with ketamine or Spravato® within 4 weeks prior to written informed consent for the research study
Patients who require an interpreter/translator for the clinic consent process, due to the infeasibility of obtaining an interpreter for research assessments, including self-rated scales
Parallel
Esketamine group
DrugThe recommended dosing for Spravato is: Weeks 1-4: Starting Day 1 dose: \< 65 years: 56 mg ≥ 65 years: 28 mg Subsequent doses: 28 mg (≥ 65 years), 56 mg or 84 mg twice weekly Weeks 5-8: 28 mg (≥ 65 years), 56 mg or 84 mg once weekly From Week 9: 28 mg (≥ 65 years), 56 mg or 84 mg every 2 weeks or once weekly
Racemic ketamine
DrugTypically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted as needed using an ascending dose titration schedule: 1. 0.5 mg/kg 2. 0.6 mg/kg 3. 0.75 mg/kg 4. 0.9 mg/kg 5. Further increments by 0.1-0.2 mg/kg, up to max 1.5 mg/kg
Montgomery-Asberg Depression Rating Scale (MADRS)
Change in score on the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is sensitive to change, and is commonly used for treatment trials in depression. MADRS includes questions on ten symptoms, each of which yields a score of 0 to 6. The total score ranges from 0 to 60. The higher the MADRS score the more severe the depression. Cutoff points are for levels of depression are: 0 to 6: normal /symptom absent 7 to 19: mild depression 20 to 34: moderate depression 35 to 60: severe depression.
Montgomery-Asberg Depression Rating Scale (MADRS) score
Score on the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is sensitive to change, and is commonly used for treatment trials in depression. See outcome 1 for minimum and maximum values, and whether higher scores indicate a better or worse outcome.
Response - Montgomery-Asberg Depression Rating Scale (MADRS)
Response (≥50% improvement in MADRS)
Remission - Montgomery-Asberg Depression Rating Scale (MADRS)
Remission (MADRS score ≤10)
DASS-21
Depression, Anxiety and Stress Scale (DASS-21) - will be used to measure psychological distress. It consists of three 7-item subscales, with items scored on a 4-point Likert scale (0-3) and summed to obtain subscale scores.
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The George Institute
Lead sponsor
The University of New South Wales
Collaborator
