Major Depressive Episode
Conditions
Keywords
oral ketamine, major depressive episodes, oral midazolam
Brief summary
Patients with depression are acutely distressed, often suicidal, and unable to meet the demands of everyday life. If proven effective in a rigorously conducted multicenter randomized controlled trial (RCT), oral ketamine would provide an affordable and scalable, intervention suitable for integration into routine psychiatric services.This study will establish an indigenous, cost-effective therapeutic strategy that could improve accessibility, hasten therapeutic response, and inform treatment guidelines, if found to be safe and effective.
Detailed description
Background: Conventional antidepressant treatment for major depressive episodes typically requires 3-6 weeks of drug use before meaningful clinical improvement is noted. Consequently, patients have to put their lives and responsibilities on hold while waiting for a therapeutic response. Problem statement and rationale: There is a distinct need for a safe, acceptable, and effective, rapidly acting antidepressant in MDE to limit the impact on daily life. As an inexpensive, generic medication administered through a convenient route, oral ketamine has the potential to overcome the logistical barriers associated with existing ketamine formulations. If proven effective in a rigorous multicenter randomized controlled trial (RCT), oral ketamine would provide an affordable, scalable, and pragmatic intervention suitable for integration into routine psychiatric services. Objectives- Primary: To assess the efficacy of adjunctive oral ketamine vs oral midazolam on clinical depression ratings at the end of study week 3- primary endpoint assessed using Hamilton Depression rating scale. Secondary: To assess the efficacy of adjunctive oral ketamine vs oral midazolam on clinical depression ratings at study day 2, day 7, and end of study weeks 2 and 4 and suicide ideation ratings at study day 2, study day 7, end of study week 2, week 3, and week 4. To assess the efficacy of adjunctive oral ketamine vs oral midazolam on between-group response and remission rates, self-rated functioning, and self-rated quality of life at the end of study week 2, week 3, and week 4. To compare psychophysiological and adverse effects between groups during each treatment session until the end (at 2 hours) and to compare adverse effects between groups at study day 2, day 7, and the end of study week 2, week 3, and week 4. Methodology: This study uses a randomized, double-blind, active-placebo controlled, multicenter, RCT design to compare the efficacy and safety of repeated dosing with adjunctive oral ketamine vs oral midazolam in patients with moderate to severe MDE. Safety and efficacy endpoints will be assessed by separate outcome raters. Expected outcomes: This study will establish an indigenous, cost-effective therapeutic strategy that could improve accessibility, hasten therapeutic response, and inform treatment guidelines, if found to be safe and effective.
Interventions
DRUGOral ketamine
Nine sessions of oral ketamine
DRUGOral midazolam
Nine sessions of oral midazolam
Sponsors
Jawaharlal Institute of Postgraduate Medical Education & Research
Indian Council of Medical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Consenting adult outpatients or inpatients with at least moderately severe major depressive episode (MDE), denoted by HAM- D more than or equal to 20, associated with major depressive disorder or bipolar disorder, with diagnosis confirmed using a structured diagnostic interview.
Exclusion criteria
* Patients with co-morbid obsessive-compulsive disorder or intellectual disability disorder or co-morbid substance dependence other than nicotine or patients concurrently receiving neuromodulation treatments or those with psychotic symptoms. Patients with current or ongoing suicide risk, such as active suicidal ideation with a specific plan or some intent in the last 3 days, will be excluded if they are treated as outpatients. Patients in whom, in the subjective opinion of the PI, the MDE symptoms appear to be significantly driven by acute life events or circumstances. Patients with abnormalities of concern detected in the electrocardiogram, or with uncontrolled hypertension or those with ongoing pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HAM-D) | End of study week 3 (±2 days) | Endpoint HAM-D scores. Minimum 0 and maximum 52. Higher scores denote worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HAM-D) | Study day 2 (± 1 day), day 7 (± 1 day), and the end of study weeks 2 (± 1 day) and week 4 (±2 days) | Endpoint HAM-D scores. Minimum 0 and maximum 52. Higher scores denote worse outcomes. |
| Montgomery-Asberg Depression Rating Scale (MADRS) | End of study day 2 (± 1 day), day 7 (± 1 day), end of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days) | Endpoint MADRS scores. Minimum 0 and maximum 60. Higher scores denote worse outcomes. |
| Patient Health Questionnaire (PHQ)-9 | End of study day 2 (± 1 day), day 7 (± 1 day), end of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days) | Endpoint PHQ scores. Minimum 0 and maximum 27. Higher scores denote worse outcomes. |
| Hamilton Depression Rating Scale (HAM-D)/Montgomery-Asberg Depression Rating Scale (MADRS) | End of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days) | Response and remisssion rates. HAM-D-Minimum 0 and maximum 52. MADRS-Minimum 0 and maximum 60.For both scales, higher scores denote worse outcomes. |
| Visual Analogue Scale for self-rated functioning & quality of life | End of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days) | Percentage change from baseline. Scores range from 0 to 100. Higher scores denote better outcome. |
| Intrasession adverse effects checklist | During each treatment session until the end (at 2 hours) | Proportion and frequency of adverse effects. Checklist used for adverse effects. |
| Systematic assessment for treatment-emergent effects (SAFTEE) checklist | At study day 2 (± 1 day), day 7 (± 1 day), end of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days) | Proportion and frequency of adverse effects. Checklist used for the systematic assessment of side effects in clinical trials |
Countries
India
Contacts
CONTACTVikas Menon, MD
Outcome results
None listed