A Phase 3 interventional study of Oral ketamine and Oral midazolam in Major Depressive Episode, sponsored by Jawaharlal Institute of Postgraduate Medical Education & Research. Not yet recruiting at 5 sites in India. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-01.
Sponsored by Jawaharlal Institute of Postgraduate Medical Education & Research · Phase 3, Interventional, and Treatment
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.
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.
Jawaharlal Institute of Postgraduate Medical Education & Research is the lead sponsor of 12 studies on the registry; 1 is open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The comparator arm will receive flexibly-dosed oral midazolam (5-7.5mg across all nine sessions, guided based on psychophysiological response to preserve the integrity of blinding), which will also be administered in approximately 200 mL of water, and sipped across 20-30 minutes
Drug: Oral midazolam
In the first session, oral ketamine will be administered as a fixed 150 mg dose diluted in approximately 200 mL water and sipped across 20-30 minutes. In sessions 2-9 for oral ketamine, the dose will be lowered to 100-125mg in those who do not tolerate 150mg. If patients tolerate the first session well, the dose of ketamine will be increased to 175mg in the second session. If there is a negligible benefit and the intervention is tolerated, the dose of ketamine will be increased to 200 mg in the third session. Further increase in ketamine will be done in the last week to 250mg, if deemed necessary, due to suboptimal response. Participants will remain nil per oral from one hour before until two hours after each session. Blood pressure and pulse rate will be monitored every 15 minutes for one hour or until normalization. Benzodiazepines such as clonazepam will be permitted for anxiety or agitation
Drug: Oral ketamine
Nine sessions of oral ketamine
Nine sessions of oral midazolam
Hamilton Depression Rating Scale (HAM-D)
Endpoint HAM-D scores. Minimum 0 and maximum 52. Higher scores denote worse outcomes.
Time frame: End of study week 3 (±2 days)
Hamilton Depression Rating Scale (HAM-D)
Endpoint HAM-D scores. Minimum 0 and maximum 52. Higher scores denote worse outcomes.
Time frame: Study day 2 (± 1 day), day 7 (± 1 day), and the end of study weeks 2 (± 1 day) and week 4 (±2 days)
Montgomery-Asberg Depression Rating Scale (MADRS)
Endpoint MADRS scores. Minimum 0 and maximum 60. Higher scores denote worse outcomes.
Time frame: 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)
Patient Health Questionnaire (PHQ)-9
Endpoint PHQ scores. Minimum 0 and maximum 27. Higher scores denote worse outcomes.
Time frame: 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)
Hamilton Depression Rating Scale (HAM-D)/Montgomery-Asberg Depression Rating Scale (MADRS)
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.
Time frame: End of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days)
Visual Analogue Scale for self-rated functioning & quality of life
Percentage change from baseline. Scores range from 0 to 100. Higher scores denote better outcome.
Time frame: End of study week 2 (±1 day), week 3 (± 2 days), and week 4 (± 2 days)
Intrasession adverse effects checklist
Proportion and frequency of adverse effects. Checklist used for adverse effects.
Time frame: During each treatment session until the end (at 2 hours)
Systematic assessment for treatment-emergent effects (SAFTEE) checklist
Proportion and frequency of adverse effects. Checklist used for the systematic assessment of side effects in clinical trials
Time frame: 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)
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Ketamine
Jawaharlal Institute of Postgraduate Medical Education & Research