A Study Comparing Oral Ketamine With Oral Midazolam for the Treatment of Major Depressive Episodes

Overview

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: We will use a randomized, double-blind, active-placebo controlled, multicenter, RCT design to compare the efficacy and safety of repeated dosing with adjunctive oral racemic 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.